Miriam E. Tucker

Minimizing dietary consumption of simple sugars may help alleviate symptoms of gastroesophageal reflux disease (GERD), new data suggest.

People who consumed lower quantities of simple sugars experienced significant improvement in total acid exposure time, number of reflux episodes, and subjective reports of heartburn and reflux symptoms, compared with those consuming higher amounts of simple sugars, the authors report.

The authors call their study the first randomized controlled diet intervention trial to investigate both the amount and type of carbohydrate on symptomatic GERD and one of only a few to investigate any type of dietary intervention for GERD.

“There’s really almost no rigorous scientific evidence on any of the foods or ingredients or nutrients that are often recommended to avoid if you have GERD,” corresponding author Heidi J. Silver, RD, PhD, told this news organization. Dr. Silver is research professor of medicine at Vanderbilt University School of Medicine and director of the Vanderbilt Diet, Body Composition, and Human Metabolism Core in Nashville, Tenn.

Even the avoidance of fatty foods, which has been long promoted as part of GERD management, has little evidence to support it.

“With fat, there’s some belief that it may slow down gastric emptying. Therefore, if you had slower gastric emptying, you would have a longer time for the food to put pressure on the lower esophageal sphincter and create an environment for reflux. So, it’s kind of conceptually what is thought but not really tested,” she notes.

The findings were published online in the American Journal of Gastroenterology.
 

Greatest symptom reduction with low simple carb intake

To test the role of dietary carbohydrates, Dr. Silver and her colleagues randomly assigned 98 U.S. veterans with symptomatic GERD to intake of one of four diets with varying carbohydrate types and amounts for 9 weeks: high total/high simple (the control group), high total/low simple, low total/high simple, or low total/low simple. The total caloric intake was approximately the same for all groups.

At baseline, the average total carbohydrate consumption was 43.7% of calories, and the average simple sugar intake was 116.5 g/d. The two “low-total” groups averaged about a 10% reduction in carbohydrate calories. The “low-simple” groups reduced simple sugars by about half.

There were no changes in body weight in the control group, whereas all three of the other groups lost some weight, ranging from 1.5-2.0 kg (3.3-4.4 lb) despite calorie totals designed for weight maintenance.

There was a significant effect of diet on the two primary outcomes, total esophageal acid exposure time, and total number of reflux episodes, as measured by 24-hour ambulatory pH monitoring. The change in total acid exposure time was significantly greater for the high total/low simple group, compared with the high total/high simple group.

The participants’ ratings of symptoms assessed by the Gastroesophageal Reflux Disease Questionnaire and the GERD Symptom Assessment Scale, including heartburn frequency and severity, pain in throat/chest, and sleep disturbance, improved in all modified diet groups, compared with the control group. The mean degree of improvement in heartburn and regurgitation was twice as great for the modified diets, compared with the controls, and was greatest for the two “low-simple” carb groups.

Dr. Silver and colleagues hypothesize that the differential effects of the diets may relate to the way that dietary carbohydrates are sensed in the gastrointestinal tract after being enzymatically degraded into monosaccharides, possibly affecting lower esophageal tone via the effects of gut-derived hormones including ghrelin and glucagon-like peptide 1 that are secreted in response to macronutrient intake.

Although more data are needed about the effects of carbohydrates in GERD, Dr. Silver advised, “I do think it would be smart for clinicians, when they’re discussing diet, that they bring up the simple sugars. There’s no potential harm in reducing simple sugars. You’re only benefiting yourself in multiple ways. We know that the consumption of simple sugars is extremely excessive, not just in America but worldwide.”

Asked to comment, Philip O. Katz, MD, professor of medicine and director of the GI Function Laboratories at Weill Cornell Medicine, New York, told this news organization that “this is one of the better-designed studies with a lot of care looking at a lot of endpoints that are intriguing and useful.”

“What it says to me is there is potential for nonpharmacologic interventions for GERD that include diet change for helping patients,” he said. “This shows promise for a diet that doesn’t just concentrate on fat or acidic products and is a possible way of augmenting reflux treatment.”

However, Dr. Katz cautioned, “I don’t think anybody should do more with a 9-week study than look at it as good potential.”

“I would tell patients that this is something that they might try, but I wouldn’t make it a rigid requirement based on these data,” he added. “If I were involved in this study, the next thing I would do is transition it to real life and look at compliance to see if results were sustained at 18 weeks or 6 months.”
 

Diet part of an ‘overall reflux program’

Overall, Dr. Katz, who was the first author of the American College of Gastroenterology’s Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease, pointed out that the main nonpharmacologic advice for GERD management includes “Eat smaller meals, don’t eat before bed, don’t lie down after you eat, and reduce any individually known trigger foods.”

Essentially, he views dietary interventions as complementary to medication and other interventions.

“When people really have GERD – not just heartburn – dietary change is an adjunct,” Dr. Katz said. “GERD is a real disease, like diabetes. For some with GERD, maybe this is the only thing they need to do. But, in general, this will be an adjunct to augment an overall reflux program.”

And that program, both Dr. Silver and Dr. Katz said, should include referral to a dietitian or nutritionist.

“If you’re going to invest time in getting your patients to change their diet, it should be done with professional help, a qualified nutritionist who can work with the patient. This should not be a fad,” Dr. Katz said.

Dr. Silver noted, “In contrast to a physician, the dietitian looks at everything the person is eating. If they’re consuming a lot of simple sugars, I certainly would make that recommendation to reduce, along with other recommendations for GERD. It could be easily incorporated. We included examples in the paper of what we did to achieve that reduction and some things clinicians could focus on.”

One obvious approach, she said, is to advise patients to cut the amount of sugared soda they’re drinking, if not eliminate it entirely.

The study was funded by a VA Merit Award. Dr. Silver has no further disclosures. Dr. Katz is a consultant for Phathom Pharmaceuticals and Sebella Pharmaceuticals and serves on an advisory board for AstraZeneca.

A version of this article first appeared on Medscape.com.

Minimizing dietary consumption of simple sugars may help alleviate symptoms of gastroesophageal reflux disease (GERD), new data suggest.

People who consumed lower quantities of simple sugars experienced significant improvement in total acid exposure time, number of reflux episodes, and subjective reports of heartburn and reflux symptoms, compared with those consuming higher amounts of simple sugars, the authors report.

The authors call their study the first randomized controlled diet intervention trial to investigate both the amount and type of carbohydrate on symptomatic GERD and one of only a few to investigate any type of dietary intervention for GERD.

“There’s really almost no rigorous scientific evidence on any of the foods or ingredients or nutrients that are often recommended to avoid if you have GERD,” corresponding author Heidi J. Silver, RD, PhD, told this news organization. Dr. Silver is research professor of medicine at Vanderbilt University School of Medicine and director of the Vanderbilt Diet, Body Composition, and Human Metabolism Core in Nashville, Tenn.

Even the avoidance of fatty foods, which has been long promoted as part of GERD management, has little evidence to support it.

“With fat, there’s some belief that it may slow down gastric emptying. Therefore, if you had slower gastric emptying, you would have a longer time for the food to put pressure on the lower esophageal sphincter and create an environment for reflux. So, it’s kind of conceptually what is thought but not really tested,” she notes.

The findings were published online in the American Journal of Gastroenterology.
 

Greatest symptom reduction with low simple carb intake

To test the role of dietary carbohydrates, Dr. Silver and her colleagues randomly assigned 98 U.S. veterans with symptomatic GERD to intake of one of four diets with varying carbohydrate types and amounts for 9 weeks: high total/high simple (the control group), high total/low simple, low total/high simple, or low total/low simple. The total caloric intake was approximately the same for all groups.

At baseline, the average total carbohydrate consumption was 43.7% of calories, and the average simple sugar intake was 116.5 g/d. The two “low-total” groups averaged about a 10% reduction in carbohydrate calories. The “low-simple” groups reduced simple sugars by about half.

There were no changes in body weight in the control group, whereas all three of the other groups lost some weight, ranging from 1.5-2.0 kg (3.3-4.4 lb) despite calorie totals designed for weight maintenance.

There was a significant effect of diet on the two primary outcomes, total esophageal acid exposure time, and total number of reflux episodes, as measured by 24-hour ambulatory pH monitoring. The change in total acid exposure time was significantly greater for the high total/low simple group, compared with the high total/high simple group.

The participants’ ratings of symptoms assessed by the Gastroesophageal Reflux Disease Questionnaire and the GERD Symptom Assessment Scale, including heartburn frequency and severity, pain in throat/chest, and sleep disturbance, improved in all modified diet groups, compared with the control group. The mean degree of improvement in heartburn and regurgitation was twice as great for the modified diets, compared with the controls, and was greatest for the two “low-simple” carb groups.

Dr. Silver and colleagues hypothesize that the differential effects of the diets may relate to the way that dietary carbohydrates are sensed in the gastrointestinal tract after being enzymatically degraded into monosaccharides, possibly affecting lower esophageal tone via the effects of gut-derived hormones including ghrelin and glucagon-like peptide 1 that are secreted in response to macronutrient intake.

Although more data are needed about the effects of carbohydrates in GERD, Dr. Silver advised, “I do think it would be smart for clinicians, when they’re discussing diet, that they bring up the simple sugars. There’s no potential harm in reducing simple sugars. You’re only benefiting yourself in multiple ways. We know that the consumption of simple sugars is extremely excessive, not just in America but worldwide.”

Asked to comment, Philip O. Katz, MD, professor of medicine and director of the GI Function Laboratories at Weill Cornell Medicine, New York, told this news organization that “this is one of the better-designed studies with a lot of care looking at a lot of endpoints that are intriguing and useful.”

“What it says to me is there is potential for nonpharmacologic interventions for GERD that include diet change for helping patients,” he said. “This shows promise for a diet that doesn’t just concentrate on fat or acidic products and is a possible way of augmenting reflux treatment.”

However, Dr. Katz cautioned, “I don’t think anybody should do more with a 9-week study than look at it as good potential.”

“I would tell patients that this is something that they might try, but I wouldn’t make it a rigid requirement based on these data,” he added. “If I were involved in this study, the next thing I would do is transition it to real life and look at compliance to see if results were sustained at 18 weeks or 6 months.”
 

Diet part of an ‘overall reflux program’

Overall, Dr. Katz, who was the first author of the American College of Gastroenterology’s Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease, pointed out that the main nonpharmacologic advice for GERD management includes “Eat smaller meals, don’t eat before bed, don’t lie down after you eat, and reduce any individually known trigger foods.”

Essentially, he views dietary interventions as complementary to medication and other interventions.

“When people really have GERD – not just heartburn – dietary change is an adjunct,” Dr. Katz said. “GERD is a real disease, like diabetes. For some with GERD, maybe this is the only thing they need to do. But, in general, this will be an adjunct to augment an overall reflux program.”

And that program, both Dr. Silver and Dr. Katz said, should include referral to a dietitian or nutritionist.

“If you’re going to invest time in getting your patients to change their diet, it should be done with professional help, a qualified nutritionist who can work with the patient. This should not be a fad,” Dr. Katz said.

Dr. Silver noted, “In contrast to a physician, the dietitian looks at everything the person is eating. If they’re consuming a lot of simple sugars, I certainly would make that recommendation to reduce, along with other recommendations for GERD. It could be easily incorporated. We included examples in the paper of what we did to achieve that reduction and some things clinicians could focus on.”

One obvious approach, she said, is to advise patients to cut the amount of sugared soda they’re drinking, if not eliminate it entirely.

The study was funded by a VA Merit Award. Dr. Silver has no further disclosures. Dr. Katz is a consultant for Phathom Pharmaceuticals and Sebella Pharmaceuticals and serves on an advisory board for AstraZeneca.

A version of this article first appeared on Medscape.com.

Minimizing dietary consumption of simple sugars may help alleviate symptoms of gastroesophageal reflux disease (GERD), new data suggest.

People who consumed lower quantities of simple sugars experienced significant improvement in total acid exposure time, number of reflux episodes, and subjective reports of heartburn and reflux symptoms, compared with those consuming higher amounts of simple sugars, the authors report.

The authors call their study the first randomized controlled diet intervention trial to investigate both the amount and type of carbohydrate on symptomatic GERD and one of only a few to investigate any type of dietary intervention for GERD.

“There’s really almost no rigorous scientific evidence on any of the foods or ingredients or nutrients that are often recommended to avoid if you have GERD,” corresponding author Heidi J. Silver, RD, PhD, told this news organization. Dr. Silver is research professor of medicine at Vanderbilt University School of Medicine and director of the Vanderbilt Diet, Body Composition, and Human Metabolism Core in Nashville, Tenn.

Even the avoidance of fatty foods, which has been long promoted as part of GERD management, has little evidence to support it.

“With fat, there’s some belief that it may slow down gastric emptying. Therefore, if you had slower gastric emptying, you would have a longer time for the food to put pressure on the lower esophageal sphincter and create an environment for reflux. So, it’s kind of conceptually what is thought but not really tested,” she notes.

The findings were published online in the American Journal of Gastroenterology.
 

Greatest symptom reduction with low simple carb intake

To test the role of dietary carbohydrates, Dr. Silver and her colleagues randomly assigned 98 U.S. veterans with symptomatic GERD to intake of one of four diets with varying carbohydrate types and amounts for 9 weeks: high total/high simple (the control group), high total/low simple, low total/high simple, or low total/low simple. The total caloric intake was approximately the same for all groups.

At baseline, the average total carbohydrate consumption was 43.7% of calories, and the average simple sugar intake was 116.5 g/d. The two “low-total” groups averaged about a 10% reduction in carbohydrate calories. The “low-simple” groups reduced simple sugars by about half.

There were no changes in body weight in the control group, whereas all three of the other groups lost some weight, ranging from 1.5-2.0 kg (3.3-4.4 lb) despite calorie totals designed for weight maintenance.

There was a significant effect of diet on the two primary outcomes, total esophageal acid exposure time, and total number of reflux episodes, as measured by 24-hour ambulatory pH monitoring. The change in total acid exposure time was significantly greater for the high total/low simple group, compared with the high total/high simple group.

The participants’ ratings of symptoms assessed by the Gastroesophageal Reflux Disease Questionnaire and the GERD Symptom Assessment Scale, including heartburn frequency and severity, pain in throat/chest, and sleep disturbance, improved in all modified diet groups, compared with the control group. The mean degree of improvement in heartburn and regurgitation was twice as great for the modified diets, compared with the controls, and was greatest for the two “low-simple” carb groups.

Dr. Silver and colleagues hypothesize that the differential effects of the diets may relate to the way that dietary carbohydrates are sensed in the gastrointestinal tract after being enzymatically degraded into monosaccharides, possibly affecting lower esophageal tone via the effects of gut-derived hormones including ghrelin and glucagon-like peptide 1 that are secreted in response to macronutrient intake.

Although more data are needed about the effects of carbohydrates in GERD, Dr. Silver advised, “I do think it would be smart for clinicians, when they’re discussing diet, that they bring up the simple sugars. There’s no potential harm in reducing simple sugars. You’re only benefiting yourself in multiple ways. We know that the consumption of simple sugars is extremely excessive, not just in America but worldwide.”

Asked to comment, Philip O. Katz, MD, professor of medicine and director of the GI Function Laboratories at Weill Cornell Medicine, New York, told this news organization that “this is one of the better-designed studies with a lot of care looking at a lot of endpoints that are intriguing and useful.”

“What it says to me is there is potential for nonpharmacologic interventions for GERD that include diet change for helping patients,” he said. “This shows promise for a diet that doesn’t just concentrate on fat or acidic products and is a possible way of augmenting reflux treatment.”

However, Dr. Katz cautioned, “I don’t think anybody should do more with a 9-week study than look at it as good potential.”

“I would tell patients that this is something that they might try, but I wouldn’t make it a rigid requirement based on these data,” he added. “If I were involved in this study, the next thing I would do is transition it to real life and look at compliance to see if results were sustained at 18 weeks or 6 months.”
 

Diet part of an ‘overall reflux program’

Overall, Dr. Katz, who was the first author of the American College of Gastroenterology’s Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease, pointed out that the main nonpharmacologic advice for GERD management includes “Eat smaller meals, don’t eat before bed, don’t lie down after you eat, and reduce any individually known trigger foods.”

Essentially, he views dietary interventions as complementary to medication and other interventions.

“When people really have GERD – not just heartburn – dietary change is an adjunct,” Dr. Katz said. “GERD is a real disease, like diabetes. For some with GERD, maybe this is the only thing they need to do. But, in general, this will be an adjunct to augment an overall reflux program.”

And that program, both Dr. Silver and Dr. Katz said, should include referral to a dietitian or nutritionist.

“If you’re going to invest time in getting your patients to change their diet, it should be done with professional help, a qualified nutritionist who can work with the patient. This should not be a fad,” Dr. Katz said.

Dr. Silver noted, “In contrast to a physician, the dietitian looks at everything the person is eating. If they’re consuming a lot of simple sugars, I certainly would make that recommendation to reduce, along with other recommendations for GERD. It could be easily incorporated. We included examples in the paper of what we did to achieve that reduction and some things clinicians could focus on.”

One obvious approach, she said, is to advise patients to cut the amount of sugared soda they’re drinking, if not eliminate it entirely.

The study was funded by a VA Merit Award. Dr. Silver has no further disclosures. Dr. Katz is a consultant for Phathom Pharmaceuticals and Sebella Pharmaceuticals and serves on an advisory board for AstraZeneca.

A version of this article first appeared on Medscape.com.

Screening children for type 1 diabetes–associated islet autoantibodies at ages 2 years and 6 years would identify most of those who go on to develop the condition by mid-adolescence, new data suggest.

Both genetic screening and islet-cell autoantibody screening for type 1 diabetes risk have become less expensive in recent years. Nonetheless, as of now, most children who receive such screening do so through programs that screen relatives of people who already have the condition, such as the global TrialNet program.

Some in the type 1 diabetes field have urged wider screening, with the rationale that knowledge of increased risk can prepare families to recognize the early signs of hyperglycemia and seek medical help to prevent the onset of diabetic ketoacidosis.

Moreover, potential therapies to prevent or delay type 1 diabetes are currently in development, including the anti-CD3 monoclonal antibody teplizumab (Tzield, Provention Bio).

However, given that the incidence of type 1 diabetes is about 1 in 300 children, any population-wide screening program would need to be implemented in the most efficient and cost-effective way possible with limited numbers of tests, say Mohamed Ghalwash, PhD, of the Center for Computational Health, IBM Research, Yorktown Heights, N.Y., and colleagues.

Results from their analysis of nearly 25,000 children from five prospective cohorts in Europe and the United States were published online  in Lancet Diabetes & Endocrinology.
 

Screening in kids feasible, but may need geographic tweaking

“Our results show that initial screening for islet autoantibodies at two ages (2 years and 6 years) is sensitive and efficient for public health translation but might require adjustment by country on the basis of population-specific disease characteristics,” Dr. Ghalwash and colleagues write.

In an accompanying editorial, pediatric endocrinologist Maria J. Redondo, MD, PhD, writes: “This study is timely because recent successes in preventing type 1 diabetes highlight the need to identify the best candidates for intervention ... This paper constitutes an important contribution to the literature.”

However, Dr. Redondo, of Baylor College of Medicine and Texas Children’s Hospital, Houston, also cautioned: “It remains to be seen whether Dr. Ghalwash and colleagues’ strategy could work in the general population, because all the participants in the combined dataset had genetic risk factors for the disease or a relative with type 1 diabetes, in whom performance is expected to be higher.”

She also noted that most participants were of northern European ancestry and that it is unknown whether the same or a similar screening strategy could be applied to individuals older than 15 years, in whom preclinical type 1 diabetes progresses more slowly.
 

Two-time childhood screening yielded high sensitivity, specificity

The data from a total of 24,662 participants were pooled from five prospective cohorts from Finland (DIPP), Germany (BABYDIAB), Sweden (DiPiS), and the United States (DAISY and DEW-IT).

All were at elevated risk for type 1 diabetes based on human leukocyte antigen (HLA) genotyping, and some had first-degree relatives with the condition. Participants were screened annually for three type 1 diabetes–associated autoantibodies up to age 15 years or the onset of type 1 diabetes.

During follow-up, 672 children developed type 1 diabetes by age 15 years and 6,050 did not. (The rest hadn’t yet reached age 15 years or type 1 diabetes onset.) The median age at first appearance of islet autoantibodies was 4.5 years.

A two-age screening strategy at 2 years and 6 years was more sensitive than screening at just one age, with a sensitivity of 82% and a positive predictive value of 79% for the development of type 1 diabetes by age 15 years.

The predictive value increased with the number of autoantibodies tested. For example, a single islet autoantibody at age 2 years indicated a 4-year risk of developing type 1 diabetes by age 5.99 years of 31%, while multiple antibody positivity at age 2 years carried a 4-year risk of 55%.

By age 6 years, the risk over the next 9 years was 39% if the test had been negative at age 2 years and 70% if the test had been positive at 2 years. But overall, a 6-year-old with multiple autoantibodies had an overall 83% risk of type 1 diabetes regardless of the test result at 2 years.

The predictive performance of sensitivity by age differed by country, suggesting that the optimal ages for autoantibody testing might differ by geographic region, Dr. Ghalwash and colleagues say.

Dr. Redondo commented, “The model might require adaptation to local factors that affect the progression and prevalence of type 1 diabetes.” And, she added, “important aspects, such as screening cost, global access, acceptability, and follow-up support will need to be addressed for this strategy to be a viable public health option.”

The study was funded by JDRF. Dr. Ghalwash and another author are employees of IBM. A third author was a JDRF employee when the research was done and is now an employee of Janssen Research and Development. Dr. Redondo has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Screening children for type 1 diabetes–associated islet autoantibodies at ages 2 years and 6 years would identify most of those who go on to develop the condition by mid-adolescence, new data suggest.

Both genetic screening and islet-cell autoantibody screening for type 1 diabetes risk have become less expensive in recent years. Nonetheless, as of now, most children who receive such screening do so through programs that screen relatives of people who already have the condition, such as the global TrialNet program.

Some in the type 1 diabetes field have urged wider screening, with the rationale that knowledge of increased risk can prepare families to recognize the early signs of hyperglycemia and seek medical help to prevent the onset of diabetic ketoacidosis.

Moreover, potential therapies to prevent or delay type 1 diabetes are currently in development, including the anti-CD3 monoclonal antibody teplizumab (Tzield, Provention Bio).

However, given that the incidence of type 1 diabetes is about 1 in 300 children, any population-wide screening program would need to be implemented in the most efficient and cost-effective way possible with limited numbers of tests, say Mohamed Ghalwash, PhD, of the Center for Computational Health, IBM Research, Yorktown Heights, N.Y., and colleagues.

Results from their analysis of nearly 25,000 children from five prospective cohorts in Europe and the United States were published online  in Lancet Diabetes & Endocrinology.
 

Screening in kids feasible, but may need geographic tweaking

“Our results show that initial screening for islet autoantibodies at two ages (2 years and 6 years) is sensitive and efficient for public health translation but might require adjustment by country on the basis of population-specific disease characteristics,” Dr. Ghalwash and colleagues write.

In an accompanying editorial, pediatric endocrinologist Maria J. Redondo, MD, PhD, writes: “This study is timely because recent successes in preventing type 1 diabetes highlight the need to identify the best candidates for intervention ... This paper constitutes an important contribution to the literature.”

However, Dr. Redondo, of Baylor College of Medicine and Texas Children’s Hospital, Houston, also cautioned: “It remains to be seen whether Dr. Ghalwash and colleagues’ strategy could work in the general population, because all the participants in the combined dataset had genetic risk factors for the disease or a relative with type 1 diabetes, in whom performance is expected to be higher.”

She also noted that most participants were of northern European ancestry and that it is unknown whether the same or a similar screening strategy could be applied to individuals older than 15 years, in whom preclinical type 1 diabetes progresses more slowly.
 

Two-time childhood screening yielded high sensitivity, specificity

The data from a total of 24,662 participants were pooled from five prospective cohorts from Finland (DIPP), Germany (BABYDIAB), Sweden (DiPiS), and the United States (DAISY and DEW-IT).

All were at elevated risk for type 1 diabetes based on human leukocyte antigen (HLA) genotyping, and some had first-degree relatives with the condition. Participants were screened annually for three type 1 diabetes–associated autoantibodies up to age 15 years or the onset of type 1 diabetes.

During follow-up, 672 children developed type 1 diabetes by age 15 years and 6,050 did not. (The rest hadn’t yet reached age 15 years or type 1 diabetes onset.) The median age at first appearance of islet autoantibodies was 4.5 years.

A two-age screening strategy at 2 years and 6 years was more sensitive than screening at just one age, with a sensitivity of 82% and a positive predictive value of 79% for the development of type 1 diabetes by age 15 years.

The predictive value increased with the number of autoantibodies tested. For example, a single islet autoantibody at age 2 years indicated a 4-year risk of developing type 1 diabetes by age 5.99 years of 31%, while multiple antibody positivity at age 2 years carried a 4-year risk of 55%.

By age 6 years, the risk over the next 9 years was 39% if the test had been negative at age 2 years and 70% if the test had been positive at 2 years. But overall, a 6-year-old with multiple autoantibodies had an overall 83% risk of type 1 diabetes regardless of the test result at 2 years.

The predictive performance of sensitivity by age differed by country, suggesting that the optimal ages for autoantibody testing might differ by geographic region, Dr. Ghalwash and colleagues say.

Dr. Redondo commented, “The model might require adaptation to local factors that affect the progression and prevalence of type 1 diabetes.” And, she added, “important aspects, such as screening cost, global access, acceptability, and follow-up support will need to be addressed for this strategy to be a viable public health option.”

The study was funded by JDRF. Dr. Ghalwash and another author are employees of IBM. A third author was a JDRF employee when the research was done and is now an employee of Janssen Research and Development. Dr. Redondo has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Screening children for type 1 diabetes–associated islet autoantibodies at ages 2 years and 6 years would identify most of those who go on to develop the condition by mid-adolescence, new data suggest.

Both genetic screening and islet-cell autoantibody screening for type 1 diabetes risk have become less expensive in recent years. Nonetheless, as of now, most children who receive such screening do so through programs that screen relatives of people who already have the condition, such as the global TrialNet program.

Some in the type 1 diabetes field have urged wider screening, with the rationale that knowledge of increased risk can prepare families to recognize the early signs of hyperglycemia and seek medical help to prevent the onset of diabetic ketoacidosis.

Moreover, potential therapies to prevent or delay type 1 diabetes are currently in development, including the anti-CD3 monoclonal antibody teplizumab (Tzield, Provention Bio).

However, given that the incidence of type 1 diabetes is about 1 in 300 children, any population-wide screening program would need to be implemented in the most efficient and cost-effective way possible with limited numbers of tests, say Mohamed Ghalwash, PhD, of the Center for Computational Health, IBM Research, Yorktown Heights, N.Y., and colleagues.

Results from their analysis of nearly 25,000 children from five prospective cohorts in Europe and the United States were published online  in Lancet Diabetes & Endocrinology.
 

Screening in kids feasible, but may need geographic tweaking

“Our results show that initial screening for islet autoantibodies at two ages (2 years and 6 years) is sensitive and efficient for public health translation but might require adjustment by country on the basis of population-specific disease characteristics,” Dr. Ghalwash and colleagues write.

In an accompanying editorial, pediatric endocrinologist Maria J. Redondo, MD, PhD, writes: “This study is timely because recent successes in preventing type 1 diabetes highlight the need to identify the best candidates for intervention ... This paper constitutes an important contribution to the literature.”

However, Dr. Redondo, of Baylor College of Medicine and Texas Children’s Hospital, Houston, also cautioned: “It remains to be seen whether Dr. Ghalwash and colleagues’ strategy could work in the general population, because all the participants in the combined dataset had genetic risk factors for the disease or a relative with type 1 diabetes, in whom performance is expected to be higher.”

She also noted that most participants were of northern European ancestry and that it is unknown whether the same or a similar screening strategy could be applied to individuals older than 15 years, in whom preclinical type 1 diabetes progresses more slowly.
 

Two-time childhood screening yielded high sensitivity, specificity

The data from a total of 24,662 participants were pooled from five prospective cohorts from Finland (DIPP), Germany (BABYDIAB), Sweden (DiPiS), and the United States (DAISY and DEW-IT).

All were at elevated risk for type 1 diabetes based on human leukocyte antigen (HLA) genotyping, and some had first-degree relatives with the condition. Participants were screened annually for three type 1 diabetes–associated autoantibodies up to age 15 years or the onset of type 1 diabetes.

During follow-up, 672 children developed type 1 diabetes by age 15 years and 6,050 did not. (The rest hadn’t yet reached age 15 years or type 1 diabetes onset.) The median age at first appearance of islet autoantibodies was 4.5 years.

A two-age screening strategy at 2 years and 6 years was more sensitive than screening at just one age, with a sensitivity of 82% and a positive predictive value of 79% for the development of type 1 diabetes by age 15 years.

The predictive value increased with the number of autoantibodies tested. For example, a single islet autoantibody at age 2 years indicated a 4-year risk of developing type 1 diabetes by age 5.99 years of 31%, while multiple antibody positivity at age 2 years carried a 4-year risk of 55%.

By age 6 years, the risk over the next 9 years was 39% if the test had been negative at age 2 years and 70% if the test had been positive at 2 years. But overall, a 6-year-old with multiple autoantibodies had an overall 83% risk of type 1 diabetes regardless of the test result at 2 years.

The predictive performance of sensitivity by age differed by country, suggesting that the optimal ages for autoantibody testing might differ by geographic region, Dr. Ghalwash and colleagues say.

Dr. Redondo commented, “The model might require adaptation to local factors that affect the progression and prevalence of type 1 diabetes.” And, she added, “important aspects, such as screening cost, global access, acceptability, and follow-up support will need to be addressed for this strategy to be a viable public health option.”

The study was funded by JDRF. Dr. Ghalwash and another author are employees of IBM. A third author was a JDRF employee when the research was done and is now an employee of Janssen Research and Development. Dr. Redondo has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Researchers published the study covered in this summary on medRxiv.org as a preprint that has not yet been peer reviewed.

Key takeaways

• The study results suggest that obesity may accelerate waning of antibody response to SARS-CoV-2 vaccination and increased breakthrough infections with COVID-19.
• The findings documented evidence of reduced neutralizing antibody capacity 6 months after primary vaccination in people with severe obesity.
• This was a large study involving about more than 3.5 million people who had received at least two doses of COVID-19 vaccine, including more than 650,000 with obesity.

Why this matters

• Obesity is associated with comorbidities that independently increase the risk for severe COVID-19, including type 2 diabetes, chronic kidney disease, and heart failure.
• The authors concluded that additional or more frequent booster doses are likely to be required to maintain protection among people with obesity against COVID-19.

Study design

• Prospective longitudinal study of the incidence and severity of COVID-19 infections and immune responses in a cohort of more than 3.5 million adults from a Scottish healthcare database who received two or three doses of COVID-19 vaccine. The data came from the study, centered at the University of Edinburgh.
• About 16% had obesity with a body mass index of 30-39.9 kg/m², and an additional 3% had severe obesity with a BMI of 40 or greater.
• Although not specified in this preprint, another said that the vaccines administered in Scotland have been the Pfizer-BioNTech and Oxford-AstraZeneca formulations.

Key results

• Between Sept. 14, 2020, and March 19, 2022, 10,983 people (0.3% of the total cohort; 6.0 events per 1,000 person-years) had severe COVID-19, consisting of 9,733 who were hospitalized and 2,207 who died (957 of those hospitalized also died).
• People with obesity or severe obesity were at higher risk of hospitalization or death from COVID-19 after both a second and third (booster) dose of vaccine.
• Compared with those with normal weight, those with severe obesity (BMI higher than 40) were at significantly increased risk for severe COVID-19 after a second vaccine dose, with an adjusted rate ratio 1.76, whereas those with standard obesity (BMI, 30-40) were at a modestly but significantly increased risk with an adjusted rate ratio of 1.11.
• Breakthrough infections after the second dose for those with severe obesity, obesity, and normal weight occurred on average at 10 weeks, 15 weeks, and 20 weeks, respectively.
• Interaction testing showed that vaccine effectiveness significantly diminished over time across BMI groups, and protection waned more rapidly as BMI increased.
• Results from immunophenotyping studies run in a subgroup of several dozen subjects with severe obesity or normal weight showed significant decrements in the robustness of antibody responses in those with severe obesity 6 months after a second or third vaccine dose.

Limitations

• The authors did not specify any limitations.

Disclosures

• The study received no commercial funding.
• One author received funding from Wellcome.

This is a summary of a preprint research study , “Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,” published by researchers primarily at the University of Cambridge (England), on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.



A version of this article first appeared on Medscape.com.

Researchers published the study covered in this summary on medRxiv.org as a preprint that has not yet been peer reviewed.

Key takeaways

• The study results suggest that obesity may accelerate waning of antibody response to SARS-CoV-2 vaccination and increased breakthrough infections with COVID-19.
• The findings documented evidence of reduced neutralizing antibody capacity 6 months after primary vaccination in people with severe obesity.
• This was a large study involving about more than 3.5 million people who had received at least two doses of COVID-19 vaccine, including more than 650,000 with obesity.

Why this matters

• Obesity is associated with comorbidities that independently increase the risk for severe COVID-19, including type 2 diabetes, chronic kidney disease, and heart failure.
• The authors concluded that additional or more frequent booster doses are likely to be required to maintain protection among people with obesity against COVID-19.

Study design

• Prospective longitudinal study of the incidence and severity of COVID-19 infections and immune responses in a cohort of more than 3.5 million adults from a Scottish healthcare database who received two or three doses of COVID-19 vaccine. The data came from the study, centered at the University of Edinburgh.
• About 16% had obesity with a body mass index of 30-39.9 kg/m², and an additional 3% had severe obesity with a BMI of 40 or greater.
• Although not specified in this preprint, another said that the vaccines administered in Scotland have been the Pfizer-BioNTech and Oxford-AstraZeneca formulations.

Key results

• Between Sept. 14, 2020, and March 19, 2022, 10,983 people (0.3% of the total cohort; 6.0 events per 1,000 person-years) had severe COVID-19, consisting of 9,733 who were hospitalized and 2,207 who died (957 of those hospitalized also died).
• People with obesity or severe obesity were at higher risk of hospitalization or death from COVID-19 after both a second and third (booster) dose of vaccine.
• Compared with those with normal weight, those with severe obesity (BMI higher than 40) were at significantly increased risk for severe COVID-19 after a second vaccine dose, with an adjusted rate ratio 1.76, whereas those with standard obesity (BMI, 30-40) were at a modestly but significantly increased risk with an adjusted rate ratio of 1.11.
• Breakthrough infections after the second dose for those with severe obesity, obesity, and normal weight occurred on average at 10 weeks, 15 weeks, and 20 weeks, respectively.
• Interaction testing showed that vaccine effectiveness significantly diminished over time across BMI groups, and protection waned more rapidly as BMI increased.
• Results from immunophenotyping studies run in a subgroup of several dozen subjects with severe obesity or normal weight showed significant decrements in the robustness of antibody responses in those with severe obesity 6 months after a second or third vaccine dose.

Limitations

• The authors did not specify any limitations.

Disclosures

• The study received no commercial funding.
• One author received funding from Wellcome.

This is a summary of a preprint research study , “Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,” published by researchers primarily at the University of Cambridge (England), on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.



A version of this article first appeared on Medscape.com.

Researchers published the study covered in this summary on medRxiv.org as a preprint that has not yet been peer reviewed.

Key takeaways

• The study results suggest that obesity may accelerate waning of antibody response to SARS-CoV-2 vaccination and increased breakthrough infections with COVID-19.
• The findings documented evidence of reduced neutralizing antibody capacity 6 months after primary vaccination in people with severe obesity.
• This was a large study involving about more than 3.5 million people who had received at least two doses of COVID-19 vaccine, including more than 650,000 with obesity.

Why this matters

• Obesity is associated with comorbidities that independently increase the risk for severe COVID-19, including type 2 diabetes, chronic kidney disease, and heart failure.
• The authors concluded that additional or more frequent booster doses are likely to be required to maintain protection among people with obesity against COVID-19.

Study design

• Prospective longitudinal study of the incidence and severity of COVID-19 infections and immune responses in a cohort of more than 3.5 million adults from a Scottish healthcare database who received two or three doses of COVID-19 vaccine. The data came from the study, centered at the University of Edinburgh.
• About 16% had obesity with a body mass index of 30-39.9 kg/m², and an additional 3% had severe obesity with a BMI of 40 or greater.
• Although not specified in this preprint, another said that the vaccines administered in Scotland have been the Pfizer-BioNTech and Oxford-AstraZeneca formulations.

Key results

• Between Sept. 14, 2020, and March 19, 2022, 10,983 people (0.3% of the total cohort; 6.0 events per 1,000 person-years) had severe COVID-19, consisting of 9,733 who were hospitalized and 2,207 who died (957 of those hospitalized also died).
• People with obesity or severe obesity were at higher risk of hospitalization or death from COVID-19 after both a second and third (booster) dose of vaccine.
• Compared with those with normal weight, those with severe obesity (BMI higher than 40) were at significantly increased risk for severe COVID-19 after a second vaccine dose, with an adjusted rate ratio 1.76, whereas those with standard obesity (BMI, 30-40) were at a modestly but significantly increased risk with an adjusted rate ratio of 1.11.
• Breakthrough infections after the second dose for those with severe obesity, obesity, and normal weight occurred on average at 10 weeks, 15 weeks, and 20 weeks, respectively.
• Interaction testing showed that vaccine effectiveness significantly diminished over time across BMI groups, and protection waned more rapidly as BMI increased.
• Results from immunophenotyping studies run in a subgroup of several dozen subjects with severe obesity or normal weight showed significant decrements in the robustness of antibody responses in those with severe obesity 6 months after a second or third vaccine dose.

Limitations

• The authors did not specify any limitations.

Disclosures

• The study received no commercial funding.
• One author received funding from Wellcome.

This is a summary of a preprint research study , “Accelerated waning of the humoral response to SARS-CoV-2 vaccines in obesity,” published by researchers primarily at the University of Cambridge (England), on medRxiv. This study has not yet been peer reviewed. The full text of the study can be found on medRxiv.org.



A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved a supplemental indication for the combination phentermine and topiramate extended-release capsules (Qsymia, Vivus) in patients aged 12 years and older with obesity.

The indication is for use as additional therapy along with a reduced-calorie diet and increased physical activity in youth with obesity, defined as a body mass index of the 95th percentile or greater when standardized for age and sex.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved a supplemental indication for the combination phentermine and topiramate extended-release capsules (Qsymia, Vivus) in patients aged 12 years and older with obesity.

The indication is for use as additional therapy along with a reduced-calorie diet and increased physical activity in youth with obesity, defined as a body mass index of the 95th percentile or greater when standardized for age and sex.

A version of this article first appeared on Medscape.com.

The U.S. Food and Drug Administration has approved a supplemental indication for the combination phentermine and topiramate extended-release capsules (Qsymia, Vivus) in patients aged 12 years and older with obesity.

The indication is for use as additional therapy along with a reduced-calorie diet and increased physical activity in youth with obesity, defined as a body mass index of the 95th percentile or greater when standardized for age and sex.

A version of this article first appeared on Medscape.com.

Boys with obesity have lower testicular volume, compared with their normal-weight counterparts, suggesting the potential for fertility problems in adulthood, new data suggest.

Testicular volume is a fertility marker directly related to sperm count that has halved in the past 40 years worldwide for unknown reasons. At the same time, childhood obesity has risen dramatically and infertility appears to have risen as well, Rossella Cannarella, MD, of the department of endocrinology and andrology, University of Catania (Italy), said at the annual meeting of the Endocrine Society.

According to recent Italian studies, between 14% and 23% of young men aged 18-19 had testicular hypotrophy. “Worryingly, we don’t know the reason for this hypotrophy. And therefore, they are at risk for future infertility,” Dr. Cannarella said during a press briefing.

Her study, which included a total of 264 male children and adolescents, also linked lower testicular volume to hyperinsulinemia and insulin resistance. “The testis is not quiescent in childhood and is sensitive to the hormone insulin. Obesity and metabolic impairment actually can have an effect and negative impact on Sertoli cell proliferation,” Dr. Cannarella said.
 

Screen testicular volume at all visits

If other studies confirm these results, she said that pediatricians should begin routinely assessing testicular volume at all visits as is now done with height and weight to identify early deflection of the testicular growth curve.

In addition, “include male infertility as a possible consequence of obesity in counseling of male obese children,” she advised.

Asked to comment, Amin Sedaghat Herati, MD, director of male infertility and men’s health at Johns Hopkins Hospital, and assistant professor of urology at Johns Hopkins Medicine, both in Baltimore, said in an interview: “I think what’s really interesting about this study is the association that they’ve made between testicular volume and obesity.”

But, he noted, “it does not implicate necessarily the development of infertility. It’s an extrapolation. So it’s a step towards the link between obesity and infertility, and it’s an important study to establish the association, but changes in testicular volume and even changes in semen panel don’t necessarily indicate fertility or infertility.”

The findings are “consistent with what we know as far as what obesity can potentially do to the activity of the cells in the testes. The authors are postulating that it’s more the support cells, called Sertoli cells, but I would say it’s probably all of the cells that are being affected by obesity and specifically elevated leptin levels,” Dr. Herati said.

He agrees with the recommendation that pediatricians screen all boys for testicular volume. “I agree it’s a good idea so they don’t miss any cases in which the testes don’t develop the way they should or any other conditions,” Dr. Herati said. “I think in general it’s a good practice, especially in the peripubertal stage, to make sure that kids are on the same growth curve and that they’re meeting their Tanner staging. [Pediatricians] should be looking at the size of the testes and tracking, maybe not at every visit, but at least on an annual basis.”

And, he noted, “I think any study that establishes a link that we can point to when we’re educating patients and parents is important.”
 

Links found between overweight/obesity, testicular hypotrophy

The study population included 61 male children and adolescents with normal weight, 53 with overweight, and 150 with obesity. Insulin resistance (Homeostatic Model Assessment for Insulin Resistance index ≥ 2.5) was present in 97 participants, 22 had prediabetes, and 3 had type 2 diabetes. Clinical data were collected retrospectively.

Among the boys aged 9-14 years, those with overweight and obesity had significantly lower testicular volume, compared with those of normal weight.

Those who were in Tanner Stage 1 were more likely to have overweight and obesity than those with normal weight, suggesting that “overweight and obese adolescents start puberty later than those of normal weight,” Dr. Cannarella said.

In the 14- to 16-year-old age group, those with insulin resistance had lower testicular volume, compared with those without insulin resistance (HOMA index < 2.5). The number of insulin-resistant adolescents was greater than that of controls in the Tanner stage 2 group.

In both the prepubertal (< 9 years) and pubertal (14-16 years) groups, hyperinsulinemia was associated with lower levels of testicular volume.

Hyperinsulinemia did not influence the timing of puberty onset.
 

No way to quantify the effect of obesity on fertility just yet

During a press briefing, Dr. Cannarella commented that obesity is likely just one of several factors influencing what appears to be an increase in male infertility over time. “It isn’t of course the only reason, but many factors in our environment have drastically changed, compared to 40 years ago, including the prevalence of heavy metals and endocrine disruptors, and of course, the change in habits and higher prevalence of metabolic disease. All of this has an impact on the proliferation of Sertoli cells in childhood and this may explain the trend toward the decline of sperm concentration and count.”

Longitudinal data are needed to establish cause and effect, she noted. “We need longitudinal studies that link the degrees of testicular volume with the degree of the sperm concentration and count starting from childhood and ending with the adult age. This is the missing link so far.”

Dr. Cannarella has reported no relevant financial relationships. Dr. Herati has reported being an advisor for Dadi, LiNA Medical, and Teleflex.

A version of this article first appeared on Medscape.com.

Boys with obesity have lower testicular volume, compared with their normal-weight counterparts, suggesting the potential for fertility problems in adulthood, new data suggest.

Testicular volume is a fertility marker directly related to sperm count that has halved in the past 40 years worldwide for unknown reasons. At the same time, childhood obesity has risen dramatically and infertility appears to have risen as well, Rossella Cannarella, MD, of the department of endocrinology and andrology, University of Catania (Italy), said at the annual meeting of the Endocrine Society.

According to recent Italian studies, between 14% and 23% of young men aged 18-19 had testicular hypotrophy. “Worryingly, we don’t know the reason for this hypotrophy. And therefore, they are at risk for future infertility,” Dr. Cannarella said during a press briefing.

Her study, which included a total of 264 male children and adolescents, also linked lower testicular volume to hyperinsulinemia and insulin resistance. “The testis is not quiescent in childhood and is sensitive to the hormone insulin. Obesity and metabolic impairment actually can have an effect and negative impact on Sertoli cell proliferation,” Dr. Cannarella said.
 

Screen testicular volume at all visits

If other studies confirm these results, she said that pediatricians should begin routinely assessing testicular volume at all visits as is now done with height and weight to identify early deflection of the testicular growth curve.

In addition, “include male infertility as a possible consequence of obesity in counseling of male obese children,” she advised.

Asked to comment, Amin Sedaghat Herati, MD, director of male infertility and men’s health at Johns Hopkins Hospital, and assistant professor of urology at Johns Hopkins Medicine, both in Baltimore, said in an interview: “I think what’s really interesting about this study is the association that they’ve made between testicular volume and obesity.”

But, he noted, “it does not implicate necessarily the development of infertility. It’s an extrapolation. So it’s a step towards the link between obesity and infertility, and it’s an important study to establish the association, but changes in testicular volume and even changes in semen panel don’t necessarily indicate fertility or infertility.”

The findings are “consistent with what we know as far as what obesity can potentially do to the activity of the cells in the testes. The authors are postulating that it’s more the support cells, called Sertoli cells, but I would say it’s probably all of the cells that are being affected by obesity and specifically elevated leptin levels,” Dr. Herati said.

He agrees with the recommendation that pediatricians screen all boys for testicular volume. “I agree it’s a good idea so they don’t miss any cases in which the testes don’t develop the way they should or any other conditions,” Dr. Herati said. “I think in general it’s a good practice, especially in the peripubertal stage, to make sure that kids are on the same growth curve and that they’re meeting their Tanner staging. [Pediatricians] should be looking at the size of the testes and tracking, maybe not at every visit, but at least on an annual basis.”

And, he noted, “I think any study that establishes a link that we can point to when we’re educating patients and parents is important.”
 

Links found between overweight/obesity, testicular hypotrophy

The study population included 61 male children and adolescents with normal weight, 53 with overweight, and 150 with obesity. Insulin resistance (Homeostatic Model Assessment for Insulin Resistance index ≥ 2.5) was present in 97 participants, 22 had prediabetes, and 3 had type 2 diabetes. Clinical data were collected retrospectively.

Among the boys aged 9-14 years, those with overweight and obesity had significantly lower testicular volume, compared with those of normal weight.

Those who were in Tanner Stage 1 were more likely to have overweight and obesity than those with normal weight, suggesting that “overweight and obese adolescents start puberty later than those of normal weight,” Dr. Cannarella said.

In the 14- to 16-year-old age group, those with insulin resistance had lower testicular volume, compared with those without insulin resistance (HOMA index < 2.5). The number of insulin-resistant adolescents was greater than that of controls in the Tanner stage 2 group.

In both the prepubertal (< 9 years) and pubertal (14-16 years) groups, hyperinsulinemia was associated with lower levels of testicular volume.

Hyperinsulinemia did not influence the timing of puberty onset.
 

No way to quantify the effect of obesity on fertility just yet

During a press briefing, Dr. Cannarella commented that obesity is likely just one of several factors influencing what appears to be an increase in male infertility over time. “It isn’t of course the only reason, but many factors in our environment have drastically changed, compared to 40 years ago, including the prevalence of heavy metals and endocrine disruptors, and of course, the change in habits and higher prevalence of metabolic disease. All of this has an impact on the proliferation of Sertoli cells in childhood and this may explain the trend toward the decline of sperm concentration and count.”

Longitudinal data are needed to establish cause and effect, she noted. “We need longitudinal studies that link the degrees of testicular volume with the degree of the sperm concentration and count starting from childhood and ending with the adult age. This is the missing link so far.”

Dr. Cannarella has reported no relevant financial relationships. Dr. Herati has reported being an advisor for Dadi, LiNA Medical, and Teleflex.

A version of this article first appeared on Medscape.com.

Boys with obesity have lower testicular volume, compared with their normal-weight counterparts, suggesting the potential for fertility problems in adulthood, new data suggest.

Testicular volume is a fertility marker directly related to sperm count that has halved in the past 40 years worldwide for unknown reasons. At the same time, childhood obesity has risen dramatically and infertility appears to have risen as well, Rossella Cannarella, MD, of the department of endocrinology and andrology, University of Catania (Italy), said at the annual meeting of the Endocrine Society.

According to recent Italian studies, between 14% and 23% of young men aged 18-19 had testicular hypotrophy. “Worryingly, we don’t know the reason for this hypotrophy. And therefore, they are at risk for future infertility,” Dr. Cannarella said during a press briefing.

Her study, which included a total of 264 male children and adolescents, also linked lower testicular volume to hyperinsulinemia and insulin resistance. “The testis is not quiescent in childhood and is sensitive to the hormone insulin. Obesity and metabolic impairment actually can have an effect and negative impact on Sertoli cell proliferation,” Dr. Cannarella said.
 

Screen testicular volume at all visits

If other studies confirm these results, she said that pediatricians should begin routinely assessing testicular volume at all visits as is now done with height and weight to identify early deflection of the testicular growth curve.

In addition, “include male infertility as a possible consequence of obesity in counseling of male obese children,” she advised.

Asked to comment, Amin Sedaghat Herati, MD, director of male infertility and men’s health at Johns Hopkins Hospital, and assistant professor of urology at Johns Hopkins Medicine, both in Baltimore, said in an interview: “I think what’s really interesting about this study is the association that they’ve made between testicular volume and obesity.”

But, he noted, “it does not implicate necessarily the development of infertility. It’s an extrapolation. So it’s a step towards the link between obesity and infertility, and it’s an important study to establish the association, but changes in testicular volume and even changes in semen panel don’t necessarily indicate fertility or infertility.”

The findings are “consistent with what we know as far as what obesity can potentially do to the activity of the cells in the testes. The authors are postulating that it’s more the support cells, called Sertoli cells, but I would say it’s probably all of the cells that are being affected by obesity and specifically elevated leptin levels,” Dr. Herati said.

He agrees with the recommendation that pediatricians screen all boys for testicular volume. “I agree it’s a good idea so they don’t miss any cases in which the testes don’t develop the way they should or any other conditions,” Dr. Herati said. “I think in general it’s a good practice, especially in the peripubertal stage, to make sure that kids are on the same growth curve and that they’re meeting their Tanner staging. [Pediatricians] should be looking at the size of the testes and tracking, maybe not at every visit, but at least on an annual basis.”

And, he noted, “I think any study that establishes a link that we can point to when we’re educating patients and parents is important.”
 

Links found between overweight/obesity, testicular hypotrophy

The study population included 61 male children and adolescents with normal weight, 53 with overweight, and 150 with obesity. Insulin resistance (Homeostatic Model Assessment for Insulin Resistance index ≥ 2.5) was present in 97 participants, 22 had prediabetes, and 3 had type 2 diabetes. Clinical data were collected retrospectively.

Among the boys aged 9-14 years, those with overweight and obesity had significantly lower testicular volume, compared with those of normal weight.

Those who were in Tanner Stage 1 were more likely to have overweight and obesity than those with normal weight, suggesting that “overweight and obese adolescents start puberty later than those of normal weight,” Dr. Cannarella said.

In the 14- to 16-year-old age group, those with insulin resistance had lower testicular volume, compared with those without insulin resistance (HOMA index < 2.5). The number of insulin-resistant adolescents was greater than that of controls in the Tanner stage 2 group.

In both the prepubertal (< 9 years) and pubertal (14-16 years) groups, hyperinsulinemia was associated with lower levels of testicular volume.

Hyperinsulinemia did not influence the timing of puberty onset.
 

No way to quantify the effect of obesity on fertility just yet

During a press briefing, Dr. Cannarella commented that obesity is likely just one of several factors influencing what appears to be an increase in male infertility over time. “It isn’t of course the only reason, but many factors in our environment have drastically changed, compared to 40 years ago, including the prevalence of heavy metals and endocrine disruptors, and of course, the change in habits and higher prevalence of metabolic disease. All of this has an impact on the proliferation of Sertoli cells in childhood and this may explain the trend toward the decline of sperm concentration and count.”

Longitudinal data are needed to establish cause and effect, she noted. “We need longitudinal studies that link the degrees of testicular volume with the degree of the sperm concentration and count starting from childhood and ending with the adult age. This is the missing link so far.”

Dr. Cannarella has reported no relevant financial relationships. Dr. Herati has reported being an advisor for Dadi, LiNA Medical, and Teleflex.

A version of this article first appeared on Medscape.com.

New data and a new documentary called “The Human Trial” together illuminate the hard work, sacrifice, and slow, iterative progress in the long search for a biological cure for type 1 diabetes.

Opening in select theaters on June 24, the film was written by Los Angeles filmmaker Lisa Hepner, who has type 1 diabetes, and codirected by Ms. Hepner and her husband Guy Mossman, who also filmed it. The couple co-own a film production company.

Abramorama

“The Human Trial” follows the personal journeys of two of the first participants in ViaCyte’s early phase 2 trial of stem cell–derived islet cell transplants, as well as those of the investigators and Ms. Hepner herself, who narrates and appears in the film, interweaving her own experience with type 1 diabetes while acting as a “bridge” between the trial’s participants and scientists. The film spans 7 years of the trial.

The timing of the film’s opening happens to follow presentations at two major medical meetings in early June of more recent islet cell transplantation data from ViaCyte and two other companies, Sernova and Vertex. Each is taking a different practical approach, with the most effective and safe technique yet to be determined.

But all are pursuing the same goal: A biological “cure” for type 1 diabetes with the aim of restoring fully functioning islet cells that can produce insulin and keep blood sugar levels in target range. Ultimately, the hope is to eliminate the need for both exogenous insulin and immunosuppression for all people with type 1 diabetes.

“Cell therapy is an attempt to drastically and substantially change the paradigm of how we actually treat type 1 diabetes,” Manasi S. Jaiman, MD, pediatric endocrinologist and chief medical officer at ViaCyte, said during a presentation at the annual meeting of the Endocrine Society.

Transplantation of cadaver-derived pancreatic islet cells to treat type 1 diabetes dates back more than 20 years to the landmark Edmonton Protocol, with many refinements since. About 1,500 recipients have received them, and roughly a quarter has maintained insulin independence after 10 years, Dr. Jaiman said.

More recently, islets derived from stem cells – either embryonic or autologous – have been used to address the supply and quality problems that arise from cadaveric (dead) donors.

Still, though, the need for lifelong immune suppression means the only current recipients are people with type 1 diabetes for whom the risk of diabetes outweighs that of immune suppression, such as those with hypoglycemic unawareness or extreme glucose swings.

Abramorama

Many research efforts are underway to counter the need for immune suppression by a variety of techniques including cell encapsulation or gene modification.

While the data thus far are encouraging, most of the reports align with what Ms. Hepner says in the film: “We all want stories with a beginning, middle, and end where all the loose pieces fit together. But clinical research is messy and hard. It doesn’t fit into a tidy headline, no matter how much you want it to.”
 

Companies use different approaches for transplanting islets

At ENDO 2022, Dr. Jaiman presented results for three patients who received pancreatic precursor (PEC-01) cells derived from ViaCyte’s proprietary pluripotent stem cell line. The cells are housed in an open delivery device about the size of a standard bandage to allow direct vascularization and are implanted in a patient’s forearm. An earlier version of the device was used in the two patients in “The Human Trial.”

All three patients experienced improved blood glucose levels with lower daily insulin doses and a rise from undetectable C-peptide to levels above 0.3 ng/mL. Of the three, the best results were seen in a 52-year-old woman with type 1 diabetes for 36 years complicated by hypoglycemic unawareness. At 1-year post transplant, her hemoglobin A1c dropped from 7.4% to 6.9%, and time in range [of ideal blood glucose] from 55% to 94%, plus she had a reduction in daily exogenous insulin use of 70%. However, at 18 months her time-in-range had dropped to about 75%.

“We are watching very closely to see what this means,” Dr. Jaiman said.

Further optimization of the approach is planned. “We’re still waiting on the bulk of the data and analyzing it ... We do realize this is a journey but we’re very excited by where we are,” she enthused.

In February 2022, ViaCyte announced it had teamed up with CRISPR Therapeutics to develop an allogeneic, gene-edited stem cell-derived product designed to produce insulin while at the same time evading the immune system.

Preliminary data from another company, Sernova, using a pouch device were presented at the 2022 annual scientific sessions of the American Diabetes Association by Piotr J. Bachul, MD, of the Transplantation Institute at the University of Chicago.

The Sernova Cell Pouch System containing cadaver islets was successfully transplanted into the abdominal wall of six of seven patients. After waiting a month to allow for vascularization, the cells are then placed into the pouch (as opposed to ViaCyte’s method where they are implanted together). The first three patients achieved islet cell graft function – with positive C-peptide – for up to 1 year, although all also required supplemental transplants into the portal vein to achieve insulin independence.

In May 2022, Sernova announced a partnership with Evotec to develop a product that will combine induced pluripotent stem cell (iPSC)-based beta cells for use with the Cell Pouch System.

Clinical testing is scheduled to begin in 2024, a Sernova representative told this news organization.

And as reported earlier in June, findings from Vertex Pharmaceuticals showed success in two patients who received that company›s investigational allogeneic stem-cell derived islets (VX-880), with the first person completely insulin independent 9 months post transplant.

In contrast to the other two companies, Vertex’s approach is to transplant the cells directly to the hepatic portal vein rather than into a subcutaneous pouch.

“The only space that has ever worked efficiently for islets is the liver because they immediately get blood. ... The subcutaneous space is an interesting place, but the problem is it’s not very well vascularized,” James F. Markmann, MD, PhD, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who worked on the Vertex trials, told this news organization.

However, the Sernova representative countered: “With the Cell Pouch transplant, not only can surgeons avoid the risks associated with [hepatic] portal vein infusion – including immediate blood-mediated inflammatory reaction, which is known to kill a large proportion of infused islets – but also liver pathologies.”

Furthermore, the cells remaining in the pouch “may be entirely removed from the patient in the event of a subsequently detected cell quality issue,” which isn’t possible with cells delivered into the portal vein.

“I think it will be interesting how it plays out,” Dr. Markmann said, referring to the field as a whole.

‘The Human Trial’ spotlights the real people behind the data

“The Human Trial” ties together the lives of two young adult study participants: a mother named Maren Badger, who qualified for the study because she regularly experienced severe low blood sugar accompanied by seizures, and Greg Romero, a father who has sight-threatening diabetic retinopathy and other complications, as well as financial hardship.

The film chronicles their experiences over 7 years after receiving the transplant. It’s not easy for either of them to undergo all the implantation and explantation procedures as well as cope with the uncertainty as to whether the transplanted cells are working.

At the same time, the researchers’ emotional and sometimes frustrating journey is shown, as are scenes following company executives to Saudi Arabia and Japan in their pursuit of trial funding.

Ms. Hepner herself is featured pursuing the film’s storyline by frequently questioning company executives, in person and virtually, as well as telling her own story.

A visit to the Banting House Historic Site in London, Ontario, with her young son gives Ms. Hepner the opportunity to explain that after Canadian surgeon Frederick Banting discovered insulin, he sold the patent to the University of Toronto for one dollar.

“One hundred years ago, insulin wasn’t a business. It was a medical breakthrough that saved millions of lives. When Banting accepted his Nobel [Prize], he famously said: ‘Insulin doesn’t belong to me, it belongs to the world.’ ... Now, there’s a $245 billion industry designed to manage our disease,” Ms. Hepner says in the film.

But, she adds: “There’s a catch-22: Biotech needs big pharma’s profits to fund clinical trials. Without that support the researchers wouldn’t have gotten this far. Like most relationships, it’s complicated.”

Nonetheless, the film ultimately uplifts. As one company executive says: “Data show the product is producing insulin in patients for the first time. ... This is a big deal. We know now that the cells work.

“We didn’t know that 5 years ago. All the pieces are there, it’s just a matter of completing the puzzle.”

The ViaCyte work presented by Dr. Jaiman received funding from the European Commission Horizon 2020, the California Institute for Regenerative Medicine, and the JDRF. Jaiman is an employee of ViaCyte. The Sernova work was funded by Sernova and JDRF. Dr. Markmann has reported serving on advisory boards for iTolerance, eGenesis, and Qihan Biotech, and being a consultant for Vertex Pharmaceuticals. Ms. Hepner and Mr. Mossman run LA-based Vox Pop Films, a production company specializing in nonfiction content and commercials. “The Human Trial” was made in collaboration with the nonprofit Beyond Type 1.

A version of this article first appeared on Medscape.com.

New data and a new documentary called “The Human Trial” together illuminate the hard work, sacrifice, and slow, iterative progress in the long search for a biological cure for type 1 diabetes.

Opening in select theaters on June 24, the film was written by Los Angeles filmmaker Lisa Hepner, who has type 1 diabetes, and codirected by Ms. Hepner and her husband Guy Mossman, who also filmed it. The couple co-own a film production company.

Abramorama

“The Human Trial” follows the personal journeys of two of the first participants in ViaCyte’s early phase 2 trial of stem cell–derived islet cell transplants, as well as those of the investigators and Ms. Hepner herself, who narrates and appears in the film, interweaving her own experience with type 1 diabetes while acting as a “bridge” between the trial’s participants and scientists. The film spans 7 years of the trial.

The timing of the film’s opening happens to follow presentations at two major medical meetings in early June of more recent islet cell transplantation data from ViaCyte and two other companies, Sernova and Vertex. Each is taking a different practical approach, with the most effective and safe technique yet to be determined.

But all are pursuing the same goal: A biological “cure” for type 1 diabetes with the aim of restoring fully functioning islet cells that can produce insulin and keep blood sugar levels in target range. Ultimately, the hope is to eliminate the need for both exogenous insulin and immunosuppression for all people with type 1 diabetes.

“Cell therapy is an attempt to drastically and substantially change the paradigm of how we actually treat type 1 diabetes,” Manasi S. Jaiman, MD, pediatric endocrinologist and chief medical officer at ViaCyte, said during a presentation at the annual meeting of the Endocrine Society.

Transplantation of cadaver-derived pancreatic islet cells to treat type 1 diabetes dates back more than 20 years to the landmark Edmonton Protocol, with many refinements since. About 1,500 recipients have received them, and roughly a quarter has maintained insulin independence after 10 years, Dr. Jaiman said.

More recently, islets derived from stem cells – either embryonic or autologous – have been used to address the supply and quality problems that arise from cadaveric (dead) donors.

Still, though, the need for lifelong immune suppression means the only current recipients are people with type 1 diabetes for whom the risk of diabetes outweighs that of immune suppression, such as those with hypoglycemic unawareness or extreme glucose swings.

Abramorama

Many research efforts are underway to counter the need for immune suppression by a variety of techniques including cell encapsulation or gene modification.

While the data thus far are encouraging, most of the reports align with what Ms. Hepner says in the film: “We all want stories with a beginning, middle, and end where all the loose pieces fit together. But clinical research is messy and hard. It doesn’t fit into a tidy headline, no matter how much you want it to.”
 

Companies use different approaches for transplanting islets

At ENDO 2022, Dr. Jaiman presented results for three patients who received pancreatic precursor (PEC-01) cells derived from ViaCyte’s proprietary pluripotent stem cell line. The cells are housed in an open delivery device about the size of a standard bandage to allow direct vascularization and are implanted in a patient’s forearm. An earlier version of the device was used in the two patients in “The Human Trial.”

All three patients experienced improved blood glucose levels with lower daily insulin doses and a rise from undetectable C-peptide to levels above 0.3 ng/mL. Of the three, the best results were seen in a 52-year-old woman with type 1 diabetes for 36 years complicated by hypoglycemic unawareness. At 1-year post transplant, her hemoglobin A1c dropped from 7.4% to 6.9%, and time in range [of ideal blood glucose] from 55% to 94%, plus she had a reduction in daily exogenous insulin use of 70%. However, at 18 months her time-in-range had dropped to about 75%.

“We are watching very closely to see what this means,” Dr. Jaiman said.

Further optimization of the approach is planned. “We’re still waiting on the bulk of the data and analyzing it ... We do realize this is a journey but we’re very excited by where we are,” she enthused.

In February 2022, ViaCyte announced it had teamed up with CRISPR Therapeutics to develop an allogeneic, gene-edited stem cell-derived product designed to produce insulin while at the same time evading the immune system.

Preliminary data from another company, Sernova, using a pouch device were presented at the 2022 annual scientific sessions of the American Diabetes Association by Piotr J. Bachul, MD, of the Transplantation Institute at the University of Chicago.

The Sernova Cell Pouch System containing cadaver islets was successfully transplanted into the abdominal wall of six of seven patients. After waiting a month to allow for vascularization, the cells are then placed into the pouch (as opposed to ViaCyte’s method where they are implanted together). The first three patients achieved islet cell graft function – with positive C-peptide – for up to 1 year, although all also required supplemental transplants into the portal vein to achieve insulin independence.

In May 2022, Sernova announced a partnership with Evotec to develop a product that will combine induced pluripotent stem cell (iPSC)-based beta cells for use with the Cell Pouch System.

Clinical testing is scheduled to begin in 2024, a Sernova representative told this news organization.

And as reported earlier in June, findings from Vertex Pharmaceuticals showed success in two patients who received that company›s investigational allogeneic stem-cell derived islets (VX-880), with the first person completely insulin independent 9 months post transplant.

In contrast to the other two companies, Vertex’s approach is to transplant the cells directly to the hepatic portal vein rather than into a subcutaneous pouch.

“The only space that has ever worked efficiently for islets is the liver because they immediately get blood. ... The subcutaneous space is an interesting place, but the problem is it’s not very well vascularized,” James F. Markmann, MD, PhD, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who worked on the Vertex trials, told this news organization.

However, the Sernova representative countered: “With the Cell Pouch transplant, not only can surgeons avoid the risks associated with [hepatic] portal vein infusion – including immediate blood-mediated inflammatory reaction, which is known to kill a large proportion of infused islets – but also liver pathologies.”

Furthermore, the cells remaining in the pouch “may be entirely removed from the patient in the event of a subsequently detected cell quality issue,” which isn’t possible with cells delivered into the portal vein.

“I think it will be interesting how it plays out,” Dr. Markmann said, referring to the field as a whole.

‘The Human Trial’ spotlights the real people behind the data

“The Human Trial” ties together the lives of two young adult study participants: a mother named Maren Badger, who qualified for the study because she regularly experienced severe low blood sugar accompanied by seizures, and Greg Romero, a father who has sight-threatening diabetic retinopathy and other complications, as well as financial hardship.

The film chronicles their experiences over 7 years after receiving the transplant. It’s not easy for either of them to undergo all the implantation and explantation procedures as well as cope with the uncertainty as to whether the transplanted cells are working.

At the same time, the researchers’ emotional and sometimes frustrating journey is shown, as are scenes following company executives to Saudi Arabia and Japan in their pursuit of trial funding.

Ms. Hepner herself is featured pursuing the film’s storyline by frequently questioning company executives, in person and virtually, as well as telling her own story.

A visit to the Banting House Historic Site in London, Ontario, with her young son gives Ms. Hepner the opportunity to explain that after Canadian surgeon Frederick Banting discovered insulin, he sold the patent to the University of Toronto for one dollar.

“One hundred years ago, insulin wasn’t a business. It was a medical breakthrough that saved millions of lives. When Banting accepted his Nobel [Prize], he famously said: ‘Insulin doesn’t belong to me, it belongs to the world.’ ... Now, there’s a $245 billion industry designed to manage our disease,” Ms. Hepner says in the film.

But, she adds: “There’s a catch-22: Biotech needs big pharma’s profits to fund clinical trials. Without that support the researchers wouldn’t have gotten this far. Like most relationships, it’s complicated.”

Nonetheless, the film ultimately uplifts. As one company executive says: “Data show the product is producing insulin in patients for the first time. ... This is a big deal. We know now that the cells work.

“We didn’t know that 5 years ago. All the pieces are there, it’s just a matter of completing the puzzle.”

The ViaCyte work presented by Dr. Jaiman received funding from the European Commission Horizon 2020, the California Institute for Regenerative Medicine, and the JDRF. Jaiman is an employee of ViaCyte. The Sernova work was funded by Sernova and JDRF. Dr. Markmann has reported serving on advisory boards for iTolerance, eGenesis, and Qihan Biotech, and being a consultant for Vertex Pharmaceuticals. Ms. Hepner and Mr. Mossman run LA-based Vox Pop Films, a production company specializing in nonfiction content and commercials. “The Human Trial” was made in collaboration with the nonprofit Beyond Type 1.

A version of this article first appeared on Medscape.com.

New data and a new documentary called “The Human Trial” together illuminate the hard work, sacrifice, and slow, iterative progress in the long search for a biological cure for type 1 diabetes.

Opening in select theaters on June 24, the film was written by Los Angeles filmmaker Lisa Hepner, who has type 1 diabetes, and codirected by Ms. Hepner and her husband Guy Mossman, who also filmed it. The couple co-own a film production company.

Abramorama

“The Human Trial” follows the personal journeys of two of the first participants in ViaCyte’s early phase 2 trial of stem cell–derived islet cell transplants, as well as those of the investigators and Ms. Hepner herself, who narrates and appears in the film, interweaving her own experience with type 1 diabetes while acting as a “bridge” between the trial’s participants and scientists. The film spans 7 years of the trial.

The timing of the film’s opening happens to follow presentations at two major medical meetings in early June of more recent islet cell transplantation data from ViaCyte and two other companies, Sernova and Vertex. Each is taking a different practical approach, with the most effective and safe technique yet to be determined.

But all are pursuing the same goal: A biological “cure” for type 1 diabetes with the aim of restoring fully functioning islet cells that can produce insulin and keep blood sugar levels in target range. Ultimately, the hope is to eliminate the need for both exogenous insulin and immunosuppression for all people with type 1 diabetes.

“Cell therapy is an attempt to drastically and substantially change the paradigm of how we actually treat type 1 diabetes,” Manasi S. Jaiman, MD, pediatric endocrinologist and chief medical officer at ViaCyte, said during a presentation at the annual meeting of the Endocrine Society.

Transplantation of cadaver-derived pancreatic islet cells to treat type 1 diabetes dates back more than 20 years to the landmark Edmonton Protocol, with many refinements since. About 1,500 recipients have received them, and roughly a quarter has maintained insulin independence after 10 years, Dr. Jaiman said.

More recently, islets derived from stem cells – either embryonic or autologous – have been used to address the supply and quality problems that arise from cadaveric (dead) donors.

Still, though, the need for lifelong immune suppression means the only current recipients are people with type 1 diabetes for whom the risk of diabetes outweighs that of immune suppression, such as those with hypoglycemic unawareness or extreme glucose swings.

Abramorama

Many research efforts are underway to counter the need for immune suppression by a variety of techniques including cell encapsulation or gene modification.

While the data thus far are encouraging, most of the reports align with what Ms. Hepner says in the film: “We all want stories with a beginning, middle, and end where all the loose pieces fit together. But clinical research is messy and hard. It doesn’t fit into a tidy headline, no matter how much you want it to.”
 

Companies use different approaches for transplanting islets

At ENDO 2022, Dr. Jaiman presented results for three patients who received pancreatic precursor (PEC-01) cells derived from ViaCyte’s proprietary pluripotent stem cell line. The cells are housed in an open delivery device about the size of a standard bandage to allow direct vascularization and are implanted in a patient’s forearm. An earlier version of the device was used in the two patients in “The Human Trial.”

All three patients experienced improved blood glucose levels with lower daily insulin doses and a rise from undetectable C-peptide to levels above 0.3 ng/mL. Of the three, the best results were seen in a 52-year-old woman with type 1 diabetes for 36 years complicated by hypoglycemic unawareness. At 1-year post transplant, her hemoglobin A1c dropped from 7.4% to 6.9%, and time in range [of ideal blood glucose] from 55% to 94%, plus she had a reduction in daily exogenous insulin use of 70%. However, at 18 months her time-in-range had dropped to about 75%.

“We are watching very closely to see what this means,” Dr. Jaiman said.

Further optimization of the approach is planned. “We’re still waiting on the bulk of the data and analyzing it ... We do realize this is a journey but we’re very excited by where we are,” she enthused.

In February 2022, ViaCyte announced it had teamed up with CRISPR Therapeutics to develop an allogeneic, gene-edited stem cell-derived product designed to produce insulin while at the same time evading the immune system.

Preliminary data from another company, Sernova, using a pouch device were presented at the 2022 annual scientific sessions of the American Diabetes Association by Piotr J. Bachul, MD, of the Transplantation Institute at the University of Chicago.

The Sernova Cell Pouch System containing cadaver islets was successfully transplanted into the abdominal wall of six of seven patients. After waiting a month to allow for vascularization, the cells are then placed into the pouch (as opposed to ViaCyte’s method where they are implanted together). The first three patients achieved islet cell graft function – with positive C-peptide – for up to 1 year, although all also required supplemental transplants into the portal vein to achieve insulin independence.

In May 2022, Sernova announced a partnership with Evotec to develop a product that will combine induced pluripotent stem cell (iPSC)-based beta cells for use with the Cell Pouch System.

Clinical testing is scheduled to begin in 2024, a Sernova representative told this news organization.

And as reported earlier in June, findings from Vertex Pharmaceuticals showed success in two patients who received that company›s investigational allogeneic stem-cell derived islets (VX-880), with the first person completely insulin independent 9 months post transplant.

In contrast to the other two companies, Vertex’s approach is to transplant the cells directly to the hepatic portal vein rather than into a subcutaneous pouch.

“The only space that has ever worked efficiently for islets is the liver because they immediately get blood. ... The subcutaneous space is an interesting place, but the problem is it’s not very well vascularized,” James F. Markmann, MD, PhD, chief of the division of transplant surgery at Massachusetts General Hospital, Boston, who worked on the Vertex trials, told this news organization.

However, the Sernova representative countered: “With the Cell Pouch transplant, not only can surgeons avoid the risks associated with [hepatic] portal vein infusion – including immediate blood-mediated inflammatory reaction, which is known to kill a large proportion of infused islets – but also liver pathologies.”

Furthermore, the cells remaining in the pouch “may be entirely removed from the patient in the event of a subsequently detected cell quality issue,” which isn’t possible with cells delivered into the portal vein.

“I think it will be interesting how it plays out,” Dr. Markmann said, referring to the field as a whole.

‘The Human Trial’ spotlights the real people behind the data

“The Human Trial” ties together the lives of two young adult study participants: a mother named Maren Badger, who qualified for the study because she regularly experienced severe low blood sugar accompanied by seizures, and Greg Romero, a father who has sight-threatening diabetic retinopathy and other complications, as well as financial hardship.

The film chronicles their experiences over 7 years after receiving the transplant. It’s not easy for either of them to undergo all the implantation and explantation procedures as well as cope with the uncertainty as to whether the transplanted cells are working.

At the same time, the researchers’ emotional and sometimes frustrating journey is shown, as are scenes following company executives to Saudi Arabia and Japan in their pursuit of trial funding.

Ms. Hepner herself is featured pursuing the film’s storyline by frequently questioning company executives, in person and virtually, as well as telling her own story.

A visit to the Banting House Historic Site in London, Ontario, with her young son gives Ms. Hepner the opportunity to explain that after Canadian surgeon Frederick Banting discovered insulin, he sold the patent to the University of Toronto for one dollar.

“One hundred years ago, insulin wasn’t a business. It was a medical breakthrough that saved millions of lives. When Banting accepted his Nobel [Prize], he famously said: ‘Insulin doesn’t belong to me, it belongs to the world.’ ... Now, there’s a $245 billion industry designed to manage our disease,” Ms. Hepner says in the film.

But, she adds: “There’s a catch-22: Biotech needs big pharma’s profits to fund clinical trials. Without that support the researchers wouldn’t have gotten this far. Like most relationships, it’s complicated.”

Nonetheless, the film ultimately uplifts. As one company executive says: “Data show the product is producing insulin in patients for the first time. ... This is a big deal. We know now that the cells work.

“We didn’t know that 5 years ago. All the pieces are there, it’s just a matter of completing the puzzle.”

The ViaCyte work presented by Dr. Jaiman received funding from the European Commission Horizon 2020, the California Institute for Regenerative Medicine, and the JDRF. Jaiman is an employee of ViaCyte. The Sernova work was funded by Sernova and JDRF. Dr. Markmann has reported serving on advisory boards for iTolerance, eGenesis, and Qihan Biotech, and being a consultant for Vertex Pharmaceuticals. Ms. Hepner and Mr. Mossman run LA-based Vox Pop Films, a production company specializing in nonfiction content and commercials. “The Human Trial” was made in collaboration with the nonprofit Beyond Type 1.

A version of this article first appeared on Medscape.com.

ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.

Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.

The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.

Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.

“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.

It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.

Lisa Nainggolan/MDedge News

Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”

Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”

But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
 

‘Experiment of nature’ revealed invisible effect of pandemic stress

The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.

Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.

Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.

There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m² (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.

More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).

The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).

Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.  

The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.

And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).

Employment changes, caring responsibilities, and worry likely causes

The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.

“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.

Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.

“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.

Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.

“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.

Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”

Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.

Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.

The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.

Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.

“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.

It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.

Lisa Nainggolan/MDedge News

Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”

Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”

But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
 

‘Experiment of nature’ revealed invisible effect of pandemic stress

The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.

Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.

Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.

There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m² (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.

More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).

The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).

Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.  

The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.

And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).

Employment changes, caring responsibilities, and worry likely causes

The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.

“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.

Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.

“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.

Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.

“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.

Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”

Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ATLANTA – Disturbances in ovulation that didn’t produce any actual changes in the menstrual cycle of women were extremely common during the first year of the COVID-19 pandemic and were linked to emotional stress, according to the findings of an “experiment of nature” that allowed for comparison with women a decade earlier.

Findings from two studies of reproductive-age women, one conducted in 2006-2008 and the other in 2020-2021, were presented by Jerilynn C. Prior, MD, at the annual meeting of the Endocrine Society.

The comparison of the two time periods yielded several novel findings. “I was taught in medical school that when women don’t eat enough they lose their period. But what we now understand is there’s a graded response to various stressors, acting through the hypothalamus in a common pathway. There is a gradation of disturbances, some of which are subclinical or not obvious,” said Dr. Prior, professor of endocrinology and metabolism at the University of British Columbia, Vancouver.

Moreover, women’s menstrual cycle lengths didn’t differ across the two time periods, despite a dramatic 63% decrement in normal ovulatory function related to increased depression, anxiety, and outside stresses that the women reported in diaries.

“Assuming that regular cycles need normal ovulation is something we should just get out of our minds. It changes our concept about what’s normal if we only know about the cycle length,” she observed.

It will be critical going forward to see whether the ovulatory disturbances have resolved as the pandemic has shifted “because there’s strong evidence that ovulatory disturbances, even with normal cycle length, are related to bone loss and some evidence it’s related to early heart attacks, breast and endometrial cancers,” Dr. Prior said during a press conference.

Lisa Nainggolan/MDedge News

Asked to comment, session moderator Genevieve Neal-Perry, MD, PhD, told this news organization: “I think what we can take away is that stress itself is a modifier of the way the brain and the gonads communicate with each other, and that then has an impact on ovulatory function.”

Dr. Neal-Perry noted that the association of stress and ovulatory disruption has been reported in various ways previously, but “clearly it doesn’t affect everyone. What we don’t know is who is most susceptible. There have been some studies showing a genetic predisposition and a genetic anomaly that actually makes them more susceptible to the impact of stress on the reproductive system.”

But the lack of data on weight change in the study cohorts is a limitation. “To me one of the more important questions was what was going on with weight. Just looking at a static number doesn’t tell you whether there were changes. We know that weight gain or weight loss can stress the reproductive axis,” noted Dr. Neal-Parry of the department of obstetrics and gynecology at the University of North Carolina at Chapel Hill.
 

‘Experiment of nature’ revealed invisible effect of pandemic stress

The women in both cohorts of the Menstruation Ovulation Study (MOS) were healthy volunteers aged 19-35 years recruited from the metropolitan Vancouver region. All were menstruating monthly and none were taking hormonal birth control. Recruitment for the second cohort had begun just prior to the March 2020 COVID-19 pandemic lockdown.

Interviewer-administered questionnaires (CaMos) covering demographics, socioeconomic status, and reproductive history, and daily diaries kept by the women (menstrual cycle diary) were identical for both cohorts.

Assessments of ovulation differed for the two studies but were cross-validated. For the earlier time period, ovulation was assessed by a threefold increase in follicular-to-luteal urinary progesterone (PdG). For the pandemic-era study, the validated quantitative basal temperature (QBT) method was used.

There were 301 women in the earlier cohort and 125 during the pandemic. Both were an average age of about 29 years and had a body mass index of about 24.3 kg/m² (within the normal range). The pandemic cohort was more racially/ethnically diverse than the earlier one and more in-line with recent census data.

More of the women were nulliparous during the pandemic than earlier (92.7% vs. 80.4%; P = .002).

The distribution of menstrual cycle lengths didn’t differ, with both cohorts averaging about 30 days (P = .893). However, while 90% of the women in the earlier cohort ovulated normally, only 37% did during the pandemic, a highly significant difference (P < .0001).

Thus, during the pandemic, 63% of women had “silent ovulatory disturbances,” either with short luteal phases after ovulation or no ovulation, compared with just 10% in the earlier cohort, “which is remarkable, unbelievable actually,” Dr. Prior remarked.  

The difference wasn’t explained by any of the demographic information collected either, including socioeconomic status, lifestyle, or reproductive history variables.

And it wasn’t because of COVID-19 vaccination, as the vaccine wasn’t available when most of the women were recruited, and of the 79 who were recruited during vaccine availability, only two received a COVID-19 vaccine during the study (and both had normal ovulation).

Employment changes, caring responsibilities, and worry likely causes

The information from the diaries was more revealing. Several diary components were far more common during the pandemic, including negative mood (feeling depressed or anxious, sleep problems, and outside stresses), self-worth, interest in sex, energy level, and appetite. All were significantly different between the two cohorts (P < .001) and between those with and without ovulatory disturbances.

“So menstrual cycle lengths and long cycles didn’t differ, but there was a much higher prevalence of silent or subclinical ovulatory disturbances, and these were related to the increased stresses that women recorded in their diaries. This means that the estrogen levels were pretty close to normal but the progesterone levels were remarkably decreased,” Dr. Prior said.

Interestingly, reported menstrual cramps were also significantly more common during the pandemic and associated with ovulatory disruption.

“That is a new observation because previously we’ve always thought that you needed to ovulate in order to even have cramps,” she commented.

Asked whether COVID-19 itself might have played a role, Dr. Prior said no woman in the study tested positive for the virus or had long COVID.

“As far as I’m aware, it was the changes in employment … and caring for elders and worry about illness in somebody you loved that was related,” she said.

Asked what she thinks the result would be if the study were conducted now, she said: “I don’t know. We’re still in a stressful time with inflation and not complete recovery, so probably the issue is still very present.”

Dr. Prior and Dr. Neal-Perry have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ATLANTA -- Liquid formulations of levothyroxine offer the possibility of allowing patients with hypothyroidism to take their medication with meals or coffee and skip the currently recommended 30- to 60-minute waiting period before doing either, new data suggest.

amenic181/Getty Images

Because food, coffee, and certain medications can interfere with intestinal absorption of levothyroxine (also known as LT4), current guidelines recommend that the drug be taken in a fasting state, typically 30-60 minutes before breakfast. However, compliance may be difficult for some patients.

Now, a potential solution may come from new evidence that liquid levothyroxine formulations that bypass the gastric dissolution phase of absorption may mitigate the interference with food and coffee.

Findings from two bioavailability studies showing no difference in comparisons of Thyquidity (levothyroxine sodium oral solution, Vertice Pharma) with or without waiting periods before consuming coffee or a high-fat meal were presented at the annual meeting of the Endocrine Society (ENDO 2022), by Vertice Pharma Medical Director Kris Washington, PharmD.

And just last month, similar data were published in Thyroid for another levothyroxine oral solution, Tirosint-SOL (IBSA). No difference in pharmacokinetic properties were found with this product with a shorter versus a longer waiting period before consuming a high-fat meal.
 

Liquid thyroxine may be less affected by food/drink but is expensive

Both products have been approved by the U.S. Food and Drug Administration, but current labeling for both still calls for a 30- to 60-minute waiting period between taking the medication and eating or drinking. Thyquidity is an oral solution of 100 µg/mL levothyroxine sodium that has been shown to be bioequivalent to one of the most popular branded levothyroxine tablets, Synthroid (AbbVie), under fasting conditions. Tirosint-SOL is also an oral solution that comes in 15 different dosage ampules.

“It is important to note that while these findings are exciting and encouraging, we do want you to continue to follow the current FDA-approved label for Thyquidity, recommending that it be taken on an empty stomach 30-60 minutes prior to breakfast and that patients continue to follow all other label instructions,” Dr. Washington said during a press briefing at ENDO 2022.

When asked whether the new data would be submitted to the FDA for a possible amendment to this message, she replied: “We’re still discussing that. We’re exploring all options. ... This is fairly new data. ... It makes sense and certainly solves a lot of the challenges for people who can’t swallow or don’t choose to swallow, or the challenges of splitting or crushing with tablets.”

Asked to comment, Benjamin J. Gigliotti, MD, a clinical thyroidologist at the University of Rochester, New York, told this news organization: “Liquid levothyroxine has the potential to be a clinically useful formulation,” noting that these recent data corroborate prior findings from Europe and elsewhere that liquid levothyroxine is absorbed more rapidly and thus may be less impacted by food or beverages.

However, Dr. Gigliotti also pointed out, “I don’t think malabsorption is a major contributor to suboptimal treatment because if [patients] malabsorb the hormone, we typically just increase their dose a little bit or ask them to take it separately, and that works just fine for most people.”

And the higher cost of the liquid products is a major issue, he noted. 

A quick search on GoodRx shows that the lowest price of Tirosint-SOL is $115.52 for a 1 month supply and Thyquidity is $181.04/month. “In the few patients where I tried to obtain Tirosint-SOL, it was not covered by insurance, even with a prior authorization,” Dr. Gigliotti commented.

In contrast, generic levothyroxine tablets are about $4/month, while a common brand name of levothyroxine tablets are $47.81/month.

“Until these liquid formulations are more widely covered by insurance for a reasonable copay, or come down in price compared to generic levothyroxine tablets, most of my patients have voiced that they’d rather deal with the inconveniences of a tablet compared to higher medication cost, especially with rising economic insecurity imposed by the COVID-19 pandemic and recent world events,” Dr. Gigliotti said.
 

Bioequivalence with shorter versus longer waits before coffee/breakfast

The Thyquidity coffee study was a single-center open-label, randomized, crossover study of 40 healthy adults randomized after a 10-hour overnight fast to 600 µg Thyquidity with water under fasting conditions or to the same dose given 5 minutes prior to drinking an 8-ounce cup of American coffee without milk or sweeteners. After a 40-day washout period, the same participants received the other treatment.

Mean serum thyroxine (T4) concentrations over 48 hours were nearly identical, demonstrating comparable bioavailability. Pharmacokinetics parameters, including area under the curve (AUC) and Cmax, were also comparable for both groups. The geometric least square mean ratios for baseline-adjusted LT4 were 96.0% for Cmax and 94% for AUC. And the corresponding 90% confidence intervals fell within the 80%-125% FDA acceptance range for absence of a food effect on bioavailability, said Dr. Washington when presenting the findings.

There was one adverse event, a decrease in blood glucose level, which was deemed to be mild and unrelated to study treatment. No deaths, serious adverse events, or discontinuations due to adverse events were reported. There were no significant changes in vital signs or on ECG.

In the second Thyquidity study of 38 healthy adults, after a 10-hour fast, the same doses were given 10 or 30 minutes prior to the consumption of a 950-calorie standardized high-fat breakfast.

Again, over 48 hours, mean serum T4 levels were comparable between the two groups. The geometric least squares mean ratios for both AUC and Cmax for baseline-adjusted LT4 were 88.7% and 85.1%, respectively. Again, the corresponding 90% confidence intervals fell within the FDA’s noninterference definition, again demonstrating lack of a food effect on bioavailability, Dr. Washington noted.

Four adverse events were reported in three participants, with three deemed to be possibly related to the medication. All were isolated lab abnormalities without clinical symptoms and deemed to be mild. Three were normal on repeat testing.

There were no deaths or serious adverse events or study discontinuations for adverse events and no significant findings for vital signs or on ECG.
 

Similar findings for Tirosint-SOL but longer-term studies needed

The recently published Tirosint-SOL study included 36 healthy volunteers randomized to single 600-µg doses of the LT4 oral solution after a 10-hour fast, either 15 or 30 minutes before eating a standardized high-fat, high-calorie meal. Mean serum total thyroxine concentration profiles were similar for both the 15- and 30-minute waits, with similar AUCs.

Geometric mean ratios for AUCs at 48 and 72 hours were 90% and 92%, respectively, and the 90% confidence intervals fell within the 80%-125% FDA boundaries, suggesting similar exposures whether taken 15 or 30 minutes before a meal.

Senior author Francesco S. Celi, MD, chair of the division of endocrinology, diabetes, and metabolism at Virginia Commonwealth University, Richmond, told this news organization: “There is an interest in providing more opportunities for patients and improving adherence to the medication. ... Whatever makes life a bit easier for patients and results in a more predictable response to treatment means down the road there will be fewer visits to the doctor to make adjustments.”

However, he said that in addition to the cost and reimbursement issue, all of these studies have been short term and not conducted in real-life settings.

“Another question is: What happens if the patient goes on low-dose LT4? The studies were conducted on much higher pharmacologic doses. But at least from a safety standpoint, there’s no specific concern.”

Dr. Washington is an employee of Vertice Pharma. Dr. Celi has received unrestricted research grants and worked as a consultant for IBSA. Dr. Gigliotti has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ATLANTA -- Liquid formulations of levothyroxine offer the possibility of allowing patients with hypothyroidism to take their medication with meals or coffee and skip the currently recommended 30- to 60-minute waiting period before doing either, new data suggest.

amenic181/Getty Images

Because food, coffee, and certain medications can interfere with intestinal absorption of levothyroxine (also known as LT4), current guidelines recommend that the drug be taken in a fasting state, typically 30-60 minutes before breakfast. However, compliance may be difficult for some patients.

Now, a potential solution may come from new evidence that liquid levothyroxine formulations that bypass the gastric dissolution phase of absorption may mitigate the interference with food and coffee.

Findings from two bioavailability studies showing no difference in comparisons of Thyquidity (levothyroxine sodium oral solution, Vertice Pharma) with or without waiting periods before consuming coffee or a high-fat meal were presented at the annual meeting of the Endocrine Society (ENDO 2022), by Vertice Pharma Medical Director Kris Washington, PharmD.

And just last month, similar data were published in Thyroid for another levothyroxine oral solution, Tirosint-SOL (IBSA). No difference in pharmacokinetic properties were found with this product with a shorter versus a longer waiting period before consuming a high-fat meal.
 

Liquid thyroxine may be less affected by food/drink but is expensive

Both products have been approved by the U.S. Food and Drug Administration, but current labeling for both still calls for a 30- to 60-minute waiting period between taking the medication and eating or drinking. Thyquidity is an oral solution of 100 µg/mL levothyroxine sodium that has been shown to be bioequivalent to one of the most popular branded levothyroxine tablets, Synthroid (AbbVie), under fasting conditions. Tirosint-SOL is also an oral solution that comes in 15 different dosage ampules.

“It is important to note that while these findings are exciting and encouraging, we do want you to continue to follow the current FDA-approved label for Thyquidity, recommending that it be taken on an empty stomach 30-60 minutes prior to breakfast and that patients continue to follow all other label instructions,” Dr. Washington said during a press briefing at ENDO 2022.

When asked whether the new data would be submitted to the FDA for a possible amendment to this message, she replied: “We’re still discussing that. We’re exploring all options. ... This is fairly new data. ... It makes sense and certainly solves a lot of the challenges for people who can’t swallow or don’t choose to swallow, or the challenges of splitting or crushing with tablets.”

Asked to comment, Benjamin J. Gigliotti, MD, a clinical thyroidologist at the University of Rochester, New York, told this news organization: “Liquid levothyroxine has the potential to be a clinically useful formulation,” noting that these recent data corroborate prior findings from Europe and elsewhere that liquid levothyroxine is absorbed more rapidly and thus may be less impacted by food or beverages.

However, Dr. Gigliotti also pointed out, “I don’t think malabsorption is a major contributor to suboptimal treatment because if [patients] malabsorb the hormone, we typically just increase their dose a little bit or ask them to take it separately, and that works just fine for most people.”

And the higher cost of the liquid products is a major issue, he noted. 

A quick search on GoodRx shows that the lowest price of Tirosint-SOL is $115.52 for a 1 month supply and Thyquidity is $181.04/month. “In the few patients where I tried to obtain Tirosint-SOL, it was not covered by insurance, even with a prior authorization,” Dr. Gigliotti commented.

In contrast, generic levothyroxine tablets are about $4/month, while a common brand name of levothyroxine tablets are $47.81/month.

“Until these liquid formulations are more widely covered by insurance for a reasonable copay, or come down in price compared to generic levothyroxine tablets, most of my patients have voiced that they’d rather deal with the inconveniences of a tablet compared to higher medication cost, especially with rising economic insecurity imposed by the COVID-19 pandemic and recent world events,” Dr. Gigliotti said.
 

Bioequivalence with shorter versus longer waits before coffee/breakfast

The Thyquidity coffee study was a single-center open-label, randomized, crossover study of 40 healthy adults randomized after a 10-hour overnight fast to 600 µg Thyquidity with water under fasting conditions or to the same dose given 5 minutes prior to drinking an 8-ounce cup of American coffee without milk or sweeteners. After a 40-day washout period, the same participants received the other treatment.

Mean serum thyroxine (T4) concentrations over 48 hours were nearly identical, demonstrating comparable bioavailability. Pharmacokinetics parameters, including area under the curve (AUC) and Cmax, were also comparable for both groups. The geometric least square mean ratios for baseline-adjusted LT4 were 96.0% for Cmax and 94% for AUC. And the corresponding 90% confidence intervals fell within the 80%-125% FDA acceptance range for absence of a food effect on bioavailability, said Dr. Washington when presenting the findings.

There was one adverse event, a decrease in blood glucose level, which was deemed to be mild and unrelated to study treatment. No deaths, serious adverse events, or discontinuations due to adverse events were reported. There were no significant changes in vital signs or on ECG.

In the second Thyquidity study of 38 healthy adults, after a 10-hour fast, the same doses were given 10 or 30 minutes prior to the consumption of a 950-calorie standardized high-fat breakfast.

Again, over 48 hours, mean serum T4 levels were comparable between the two groups. The geometric least squares mean ratios for both AUC and Cmax for baseline-adjusted LT4 were 88.7% and 85.1%, respectively. Again, the corresponding 90% confidence intervals fell within the FDA’s noninterference definition, again demonstrating lack of a food effect on bioavailability, Dr. Washington noted.

Four adverse events were reported in three participants, with three deemed to be possibly related to the medication. All were isolated lab abnormalities without clinical symptoms and deemed to be mild. Three were normal on repeat testing.

There were no deaths or serious adverse events or study discontinuations for adverse events and no significant findings for vital signs or on ECG.
 

Similar findings for Tirosint-SOL but longer-term studies needed

The recently published Tirosint-SOL study included 36 healthy volunteers randomized to single 600-µg doses of the LT4 oral solution after a 10-hour fast, either 15 or 30 minutes before eating a standardized high-fat, high-calorie meal. Mean serum total thyroxine concentration profiles were similar for both the 15- and 30-minute waits, with similar AUCs.

Geometric mean ratios for AUCs at 48 and 72 hours were 90% and 92%, respectively, and the 90% confidence intervals fell within the 80%-125% FDA boundaries, suggesting similar exposures whether taken 15 or 30 minutes before a meal.

Senior author Francesco S. Celi, MD, chair of the division of endocrinology, diabetes, and metabolism at Virginia Commonwealth University, Richmond, told this news organization: “There is an interest in providing more opportunities for patients and improving adherence to the medication. ... Whatever makes life a bit easier for patients and results in a more predictable response to treatment means down the road there will be fewer visits to the doctor to make adjustments.”

However, he said that in addition to the cost and reimbursement issue, all of these studies have been short term and not conducted in real-life settings.

“Another question is: What happens if the patient goes on low-dose LT4? The studies were conducted on much higher pharmacologic doses. But at least from a safety standpoint, there’s no specific concern.”

Dr. Washington is an employee of Vertice Pharma. Dr. Celi has received unrestricted research grants and worked as a consultant for IBSA. Dr. Gigliotti has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

ATLANTA -- Liquid formulations of levothyroxine offer the possibility of allowing patients with hypothyroidism to take their medication with meals or coffee and skip the currently recommended 30- to 60-minute waiting period before doing either, new data suggest.

amenic181/Getty Images

Because food, coffee, and certain medications can interfere with intestinal absorption of levothyroxine (also known as LT4), current guidelines recommend that the drug be taken in a fasting state, typically 30-60 minutes before breakfast. However, compliance may be difficult for some patients.

Now, a potential solution may come from new evidence that liquid levothyroxine formulations that bypass the gastric dissolution phase of absorption may mitigate the interference with food and coffee.

Findings from two bioavailability studies showing no difference in comparisons of Thyquidity (levothyroxine sodium oral solution, Vertice Pharma) with or without waiting periods before consuming coffee or a high-fat meal were presented at the annual meeting of the Endocrine Society (ENDO 2022), by Vertice Pharma Medical Director Kris Washington, PharmD.

And just last month, similar data were published in Thyroid for another levothyroxine oral solution, Tirosint-SOL (IBSA). No difference in pharmacokinetic properties were found with this product with a shorter versus a longer waiting period before consuming a high-fat meal.
 

Liquid thyroxine may be less affected by food/drink but is expensive

Both products have been approved by the U.S. Food and Drug Administration, but current labeling for both still calls for a 30- to 60-minute waiting period between taking the medication and eating or drinking. Thyquidity is an oral solution of 100 µg/mL levothyroxine sodium that has been shown to be bioequivalent to one of the most popular branded levothyroxine tablets, Synthroid (AbbVie), under fasting conditions. Tirosint-SOL is also an oral solution that comes in 15 different dosage ampules.

“It is important to note that while these findings are exciting and encouraging, we do want you to continue to follow the current FDA-approved label for Thyquidity, recommending that it be taken on an empty stomach 30-60 minutes prior to breakfast and that patients continue to follow all other label instructions,” Dr. Washington said during a press briefing at ENDO 2022.

When asked whether the new data would be submitted to the FDA for a possible amendment to this message, she replied: “We’re still discussing that. We’re exploring all options. ... This is fairly new data. ... It makes sense and certainly solves a lot of the challenges for people who can’t swallow or don’t choose to swallow, or the challenges of splitting or crushing with tablets.”

Asked to comment, Benjamin J. Gigliotti, MD, a clinical thyroidologist at the University of Rochester, New York, told this news organization: “Liquid levothyroxine has the potential to be a clinically useful formulation,” noting that these recent data corroborate prior findings from Europe and elsewhere that liquid levothyroxine is absorbed more rapidly and thus may be less impacted by food or beverages.

However, Dr. Gigliotti also pointed out, “I don’t think malabsorption is a major contributor to suboptimal treatment because if [patients] malabsorb the hormone, we typically just increase their dose a little bit or ask them to take it separately, and that works just fine for most people.”

And the higher cost of the liquid products is a major issue, he noted. 

A quick search on GoodRx shows that the lowest price of Tirosint-SOL is $115.52 for a 1 month supply and Thyquidity is $181.04/month. “In the few patients where I tried to obtain Tirosint-SOL, it was not covered by insurance, even with a prior authorization,” Dr. Gigliotti commented.

In contrast, generic levothyroxine tablets are about $4/month, while a common brand name of levothyroxine tablets are $47.81/month.

“Until these liquid formulations are more widely covered by insurance for a reasonable copay, or come down in price compared to generic levothyroxine tablets, most of my patients have voiced that they’d rather deal with the inconveniences of a tablet compared to higher medication cost, especially with rising economic insecurity imposed by the COVID-19 pandemic and recent world events,” Dr. Gigliotti said.
 

Bioequivalence with shorter versus longer waits before coffee/breakfast

The Thyquidity coffee study was a single-center open-label, randomized, crossover study of 40 healthy adults randomized after a 10-hour overnight fast to 600 µg Thyquidity with water under fasting conditions or to the same dose given 5 minutes prior to drinking an 8-ounce cup of American coffee without milk or sweeteners. After a 40-day washout period, the same participants received the other treatment.

Mean serum thyroxine (T4) concentrations over 48 hours were nearly identical, demonstrating comparable bioavailability. Pharmacokinetics parameters, including area under the curve (AUC) and Cmax, were also comparable for both groups. The geometric least square mean ratios for baseline-adjusted LT4 were 96.0% for Cmax and 94% for AUC. And the corresponding 90% confidence intervals fell within the 80%-125% FDA acceptance range for absence of a food effect on bioavailability, said Dr. Washington when presenting the findings.

There was one adverse event, a decrease in blood glucose level, which was deemed to be mild and unrelated to study treatment. No deaths, serious adverse events, or discontinuations due to adverse events were reported. There were no significant changes in vital signs or on ECG.

In the second Thyquidity study of 38 healthy adults, after a 10-hour fast, the same doses were given 10 or 30 minutes prior to the consumption of a 950-calorie standardized high-fat breakfast.

Again, over 48 hours, mean serum T4 levels were comparable between the two groups. The geometric least squares mean ratios for both AUC and Cmax for baseline-adjusted LT4 were 88.7% and 85.1%, respectively. Again, the corresponding 90% confidence intervals fell within the FDA’s noninterference definition, again demonstrating lack of a food effect on bioavailability, Dr. Washington noted.

Four adverse events were reported in three participants, with three deemed to be possibly related to the medication. All were isolated lab abnormalities without clinical symptoms and deemed to be mild. Three were normal on repeat testing.

There were no deaths or serious adverse events or study discontinuations for adverse events and no significant findings for vital signs or on ECG.
 

Similar findings for Tirosint-SOL but longer-term studies needed

The recently published Tirosint-SOL study included 36 healthy volunteers randomized to single 600-µg doses of the LT4 oral solution after a 10-hour fast, either 15 or 30 minutes before eating a standardized high-fat, high-calorie meal. Mean serum total thyroxine concentration profiles were similar for both the 15- and 30-minute waits, with similar AUCs.

Geometric mean ratios for AUCs at 48 and 72 hours were 90% and 92%, respectively, and the 90% confidence intervals fell within the 80%-125% FDA boundaries, suggesting similar exposures whether taken 15 or 30 minutes before a meal.

Senior author Francesco S. Celi, MD, chair of the division of endocrinology, diabetes, and metabolism at Virginia Commonwealth University, Richmond, told this news organization: “There is an interest in providing more opportunities for patients and improving adherence to the medication. ... Whatever makes life a bit easier for patients and results in a more predictable response to treatment means down the road there will be fewer visits to the doctor to make adjustments.”

However, he said that in addition to the cost and reimbursement issue, all of these studies have been short term and not conducted in real-life settings.

“Another question is: What happens if the patient goes on low-dose LT4? The studies were conducted on much higher pharmacologic doses. But at least from a safety standpoint, there’s no specific concern.”

Dr. Washington is an employee of Vertice Pharma. Dr. Celi has received unrestricted research grants and worked as a consultant for IBSA. Dr. Gigliotti has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Open-source automated insulin delivery systems appear to be both effective and safe in adults and children, new research finds.

Automated insulin delivery (AID) system, also known as closed-loop systems or an artificial pancreas, link an insulin pump and a continuous glucose monitor (CGM) with an algorithm that automatically adjusts insulin delivery to optimize glycemic control.

Prior to the availability of commercial AID systems, Dana Lewis, a patient with type 1 diabetes, and her partner codeveloped an algorithm that could link older versions of an insulin pump and CGM.

In 2015, they made the code and all related materials open-source, so that anyone who wanted to create their own AID system could do so. Today thousands of people worldwide with type 1 diabetes are using the systems, which are sometimes called “do-it-yourself (DIY)” AID systems although the approach has been community based.  

AID systems are not approved by any regulatory body, and despite several nonrandomized studies demonstrating their effectiveness and safety, there is still concern among some health professionals about their safety. In 2019, the U.S. Food and Drug Administration warned against the use of any nonapproved devices or algorithms. (Now, though, at least one open-source AID system algorithm is under FDA review.)

Aimed at addressing those concerns, CREATE (Community Derived Automated Insulin Delivery) is the first randomized controlled clinical trial to compare an open-source AID system to insulin pump therapy and CGM (without any communication between the two) in patients with type 1 diabetes, most of whom were naive to AID systems.

Doctors uncomfortable with open source; study provides reassurance

The findings were presented at the American Diabetes Association scientific sessions by Martin I. de Bock, PhD, a pediatric endocrinologist and senior lecturer at the University of Otago, Christchurch, New Zealand.

The study compared the most commonly used open-source AID system (using the OpenAPS algorithm from a version of AndroidAPS implemented in a smartphone with the DANA-i insulin pump and Dexcom G6 CGM) to any insulin pump plus CGM as a comparator group.

The open-source AID system led to a significant reduction in hemoglobin A1c with no major safety issues.

“The acceptance [among clinicians] of open-source systems is diverse and complicated, [with varying] personal comfort levels of seeing someone using an AID system that has no regulatory approval,” Dr. de Bock told this news organization.  

“This is one of the reasons that it was so important to conduct the CREATE trial for the many thousands of open-source AID users. Given that the trial demonstrated safety and efficacy using the most robust scientific methodology available – a long-term randomized controlled trial – it may go some way to provide assurance for providers when they are seeing people using an open-source automated system,” he said.

Asked for comment, session moderator Diana Isaacs, PharmD, CDCES, an endocrine clinical pharmacist at the Cleveland Clinic, told this news organization: “There has been concern that these systems aren’t safe, so showing the safety is important. I think people deserve choice. As long as they’re safe, patients should be able to use what they want to use, and we should support them.”

Dr. Isaacs pointed out that an advantage of open-source systems over current commercial AIDs for patients is the ability to customize glucose targets, but in CREATE, those targets were established in the protocol by the investigators.

“I think it’s nice having the data, although in the trial they had specific requirements. They had a target range and active insulin time that they were recommending. So it’s a little different than true DIY where you don’t really have those guidelines you have to follow. It is exciting, it’s very interesting, but I wouldn’t say it’s a true mirror of the real world.”
 

Open-source systems improved time-in-range, no safety issues

For the CREATE study, 100 participants were enrolled, including 50 children aged 7-15 years and 50 adults aged 16-70 years. All participants had been using insulin pumps for at least 6 months. Most of the children and about two-thirds of the adults were also using CGMs, but just 6% of the children and 18% of the adults had prior experience with AID systems.

Baseline A1c in children was 7.5% and in adults was 7.7%.

After a 4-week run-in, all patients were randomized to the open-source AID or insulin pump plus CGM for 6 months.

The final group analyzed consisted of 42 patients in the open-source AID group and 53 patients in the comparator group.

The primary outcome, the adjusted mean difference in percent time-in-range (glucose of 70-180 mg/dL) during the final 2 weeks of the 6-month trial, showed a significant difference of 14% (P < .001) with open-source AID compared with pump plus CGM only.

Time-in-range in the open-source AID group rose from 61.2% to 71.2%, while it actually dropped slightly in the comparator group, from 57.7% to 54.5%.

The proportion of patients achieving time-in-range greater than 70% with open-source AID was 60% versus just 15% with pump plus CGM.

Glycemic improvements with open-source AID were significant for adults and children and were greater for those with higher baseline A1c levels. The effect was immediate and sustained throughout the study period, “which is super-pleasing, because there was a worry that the technical burden of open source might be [leading to] dropout, but we didn’t see that. It was sustained right through to the end of the trial,” Dr. de Bock commented.

Hypoglycemic rates didn’t differ between groups, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis.
 

No more waiting: What is the future of open-source AID?

When the open-source APS was first developed, users coined the motto: “We are not waiting.” But now that the “wait” is over and several commercial AIDs have been approved by regulatory bodies, with others still in the pipeline, will people still use open-source systems?

There are no current data on people moving from DIY to commercial systems. However, Dr. de Bock said, “For most who undertook an open-source option, the precision of the settings that they can use and enjoy would mean that most would likely stick to their open source.”

Dr. Isaacs agrees: “I actually don’t think it’s going to go away in the near future, because the FDA has very specific criteria for where these [formally approved] devices can be in terms of their target ranges and requirements versus with open source you can really customize. So I still think there’s going to be a subset of people who want that customization, who want the lower targets.”

Dana Lewis, the originator of the DIY system and a CREATE coauthor, told this news organization: “I don’t believe there has been a fall-off, and in fact, I think open-source AID has continued to have ongoing uptake as awareness increases about options and as more pumps and CGMs become interoperable with various open-source AID choices.”

“I think uptake increasing is also influenced by the fact that in places like Europe, Asia, and Australia there are in-warranty on-the-market pumps that are compatible and interoperable with open-source AID. I think awareness of AID overall increases uptake of commercial and open source alike,” she said.

“Clinicians, as emphasized in recent position statements, must maintain support of the person with diabetes, irrespective of the mode of treatment they are on. ... Health care providers should be encouraged to learn from the experiences of the people who have stuck with open-source AID or switched, so that they can inform themselves of the relative strengths and benefits of each system,” Dr. de Bock advised.

Ms. Lewis noted: “We are seeing increasing awareness and comfort in endocrinologists from the community perspective, and we do hope that this study helps increase conversation and awareness of the safety and efficacy of open-source AID systems as an option for people with diabetes.”

In fact, the team published an article specifically about clinicians’ experience in CREATE. “The learning curve is similar across AID technology,” she observed.  

Findings of a 6-month continuation phase of CREATE, in which all participants used the open-source AID, are scheduled to be presented in September at the European Association for the Study of Diabetes annual meeting.

The study was funded by the Health Research Council of New Zealand, with hardware support from SOOIL Developments, South Korea; Dexcom; and Vodafone New Zealand. Dr. de Bock has reported receiving honoraria and/or research funding from Novo Nordisk, Sanofi, Pfizer, Medtronic, Lilly, Ypsomed, and Dexcom. Dr. Isaacs has reported serving as a consultant for LifeScan, Lilly, and Insulet, and as a speaker for Dexcom, Medtronic, Abbott, and Novo Nordisk. Ms. Lewis has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Open-source automated insulin delivery systems appear to be both effective and safe in adults and children, new research finds.

Automated insulin delivery (AID) system, also known as closed-loop systems or an artificial pancreas, link an insulin pump and a continuous glucose monitor (CGM) with an algorithm that automatically adjusts insulin delivery to optimize glycemic control.

Prior to the availability of commercial AID systems, Dana Lewis, a patient with type 1 diabetes, and her partner codeveloped an algorithm that could link older versions of an insulin pump and CGM.

In 2015, they made the code and all related materials open-source, so that anyone who wanted to create their own AID system could do so. Today thousands of people worldwide with type 1 diabetes are using the systems, which are sometimes called “do-it-yourself (DIY)” AID systems although the approach has been community based.  

AID systems are not approved by any regulatory body, and despite several nonrandomized studies demonstrating their effectiveness and safety, there is still concern among some health professionals about their safety. In 2019, the U.S. Food and Drug Administration warned against the use of any nonapproved devices or algorithms. (Now, though, at least one open-source AID system algorithm is under FDA review.)

Aimed at addressing those concerns, CREATE (Community Derived Automated Insulin Delivery) is the first randomized controlled clinical trial to compare an open-source AID system to insulin pump therapy and CGM (without any communication between the two) in patients with type 1 diabetes, most of whom were naive to AID systems.

Doctors uncomfortable with open source; study provides reassurance

The findings were presented at the American Diabetes Association scientific sessions by Martin I. de Bock, PhD, a pediatric endocrinologist and senior lecturer at the University of Otago, Christchurch, New Zealand.

The study compared the most commonly used open-source AID system (using the OpenAPS algorithm from a version of AndroidAPS implemented in a smartphone with the DANA-i insulin pump and Dexcom G6 CGM) to any insulin pump plus CGM as a comparator group.

The open-source AID system led to a significant reduction in hemoglobin A1c with no major safety issues.

“The acceptance [among clinicians] of open-source systems is diverse and complicated, [with varying] personal comfort levels of seeing someone using an AID system that has no regulatory approval,” Dr. de Bock told this news organization.  

“This is one of the reasons that it was so important to conduct the CREATE trial for the many thousands of open-source AID users. Given that the trial demonstrated safety and efficacy using the most robust scientific methodology available – a long-term randomized controlled trial – it may go some way to provide assurance for providers when they are seeing people using an open-source automated system,” he said.

Asked for comment, session moderator Diana Isaacs, PharmD, CDCES, an endocrine clinical pharmacist at the Cleveland Clinic, told this news organization: “There has been concern that these systems aren’t safe, so showing the safety is important. I think people deserve choice. As long as they’re safe, patients should be able to use what they want to use, and we should support them.”

Dr. Isaacs pointed out that an advantage of open-source systems over current commercial AIDs for patients is the ability to customize glucose targets, but in CREATE, those targets were established in the protocol by the investigators.

“I think it’s nice having the data, although in the trial they had specific requirements. They had a target range and active insulin time that they were recommending. So it’s a little different than true DIY where you don’t really have those guidelines you have to follow. It is exciting, it’s very interesting, but I wouldn’t say it’s a true mirror of the real world.”
 

Open-source systems improved time-in-range, no safety issues

For the CREATE study, 100 participants were enrolled, including 50 children aged 7-15 years and 50 adults aged 16-70 years. All participants had been using insulin pumps for at least 6 months. Most of the children and about two-thirds of the adults were also using CGMs, but just 6% of the children and 18% of the adults had prior experience with AID systems.

Baseline A1c in children was 7.5% and in adults was 7.7%.

After a 4-week run-in, all patients were randomized to the open-source AID or insulin pump plus CGM for 6 months.

The final group analyzed consisted of 42 patients in the open-source AID group and 53 patients in the comparator group.

The primary outcome, the adjusted mean difference in percent time-in-range (glucose of 70-180 mg/dL) during the final 2 weeks of the 6-month trial, showed a significant difference of 14% (P < .001) with open-source AID compared with pump plus CGM only.

Time-in-range in the open-source AID group rose from 61.2% to 71.2%, while it actually dropped slightly in the comparator group, from 57.7% to 54.5%.

The proportion of patients achieving time-in-range greater than 70% with open-source AID was 60% versus just 15% with pump plus CGM.

Glycemic improvements with open-source AID were significant for adults and children and were greater for those with higher baseline A1c levels. The effect was immediate and sustained throughout the study period, “which is super-pleasing, because there was a worry that the technical burden of open source might be [leading to] dropout, but we didn’t see that. It was sustained right through to the end of the trial,” Dr. de Bock commented.

Hypoglycemic rates didn’t differ between groups, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis.
 

No more waiting: What is the future of open-source AID?

When the open-source APS was first developed, users coined the motto: “We are not waiting.” But now that the “wait” is over and several commercial AIDs have been approved by regulatory bodies, with others still in the pipeline, will people still use open-source systems?

There are no current data on people moving from DIY to commercial systems. However, Dr. de Bock said, “For most who undertook an open-source option, the precision of the settings that they can use and enjoy would mean that most would likely stick to their open source.”

Dr. Isaacs agrees: “I actually don’t think it’s going to go away in the near future, because the FDA has very specific criteria for where these [formally approved] devices can be in terms of their target ranges and requirements versus with open source you can really customize. So I still think there’s going to be a subset of people who want that customization, who want the lower targets.”

Dana Lewis, the originator of the DIY system and a CREATE coauthor, told this news organization: “I don’t believe there has been a fall-off, and in fact, I think open-source AID has continued to have ongoing uptake as awareness increases about options and as more pumps and CGMs become interoperable with various open-source AID choices.”

“I think uptake increasing is also influenced by the fact that in places like Europe, Asia, and Australia there are in-warranty on-the-market pumps that are compatible and interoperable with open-source AID. I think awareness of AID overall increases uptake of commercial and open source alike,” she said.

“Clinicians, as emphasized in recent position statements, must maintain support of the person with diabetes, irrespective of the mode of treatment they are on. ... Health care providers should be encouraged to learn from the experiences of the people who have stuck with open-source AID or switched, so that they can inform themselves of the relative strengths and benefits of each system,” Dr. de Bock advised.

Ms. Lewis noted: “We are seeing increasing awareness and comfort in endocrinologists from the community perspective, and we do hope that this study helps increase conversation and awareness of the safety and efficacy of open-source AID systems as an option for people with diabetes.”

In fact, the team published an article specifically about clinicians’ experience in CREATE. “The learning curve is similar across AID technology,” she observed.  

Findings of a 6-month continuation phase of CREATE, in which all participants used the open-source AID, are scheduled to be presented in September at the European Association for the Study of Diabetes annual meeting.

The study was funded by the Health Research Council of New Zealand, with hardware support from SOOIL Developments, South Korea; Dexcom; and Vodafone New Zealand. Dr. de Bock has reported receiving honoraria and/or research funding from Novo Nordisk, Sanofi, Pfizer, Medtronic, Lilly, Ypsomed, and Dexcom. Dr. Isaacs has reported serving as a consultant for LifeScan, Lilly, and Insulet, and as a speaker for Dexcom, Medtronic, Abbott, and Novo Nordisk. Ms. Lewis has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

NEW ORLEANS – Open-source automated insulin delivery systems appear to be both effective and safe in adults and children, new research finds.

Automated insulin delivery (AID) system, also known as closed-loop systems or an artificial pancreas, link an insulin pump and a continuous glucose monitor (CGM) with an algorithm that automatically adjusts insulin delivery to optimize glycemic control.

Prior to the availability of commercial AID systems, Dana Lewis, a patient with type 1 diabetes, and her partner codeveloped an algorithm that could link older versions of an insulin pump and CGM.

In 2015, they made the code and all related materials open-source, so that anyone who wanted to create their own AID system could do so. Today thousands of people worldwide with type 1 diabetes are using the systems, which are sometimes called “do-it-yourself (DIY)” AID systems although the approach has been community based.  

AID systems are not approved by any regulatory body, and despite several nonrandomized studies demonstrating their effectiveness and safety, there is still concern among some health professionals about their safety. In 2019, the U.S. Food and Drug Administration warned against the use of any nonapproved devices or algorithms. (Now, though, at least one open-source AID system algorithm is under FDA review.)

Aimed at addressing those concerns, CREATE (Community Derived Automated Insulin Delivery) is the first randomized controlled clinical trial to compare an open-source AID system to insulin pump therapy and CGM (without any communication between the two) in patients with type 1 diabetes, most of whom were naive to AID systems.

Doctors uncomfortable with open source; study provides reassurance

The findings were presented at the American Diabetes Association scientific sessions by Martin I. de Bock, PhD, a pediatric endocrinologist and senior lecturer at the University of Otago, Christchurch, New Zealand.

The study compared the most commonly used open-source AID system (using the OpenAPS algorithm from a version of AndroidAPS implemented in a smartphone with the DANA-i insulin pump and Dexcom G6 CGM) to any insulin pump plus CGM as a comparator group.

The open-source AID system led to a significant reduction in hemoglobin A1c with no major safety issues.

“The acceptance [among clinicians] of open-source systems is diverse and complicated, [with varying] personal comfort levels of seeing someone using an AID system that has no regulatory approval,” Dr. de Bock told this news organization.  

“This is one of the reasons that it was so important to conduct the CREATE trial for the many thousands of open-source AID users. Given that the trial demonstrated safety and efficacy using the most robust scientific methodology available – a long-term randomized controlled trial – it may go some way to provide assurance for providers when they are seeing people using an open-source automated system,” he said.

Asked for comment, session moderator Diana Isaacs, PharmD, CDCES, an endocrine clinical pharmacist at the Cleveland Clinic, told this news organization: “There has been concern that these systems aren’t safe, so showing the safety is important. I think people deserve choice. As long as they’re safe, patients should be able to use what they want to use, and we should support them.”

Dr. Isaacs pointed out that an advantage of open-source systems over current commercial AIDs for patients is the ability to customize glucose targets, but in CREATE, those targets were established in the protocol by the investigators.

“I think it’s nice having the data, although in the trial they had specific requirements. They had a target range and active insulin time that they were recommending. So it’s a little different than true DIY where you don’t really have those guidelines you have to follow. It is exciting, it’s very interesting, but I wouldn’t say it’s a true mirror of the real world.”
 

Open-source systems improved time-in-range, no safety issues

For the CREATE study, 100 participants were enrolled, including 50 children aged 7-15 years and 50 adults aged 16-70 years. All participants had been using insulin pumps for at least 6 months. Most of the children and about two-thirds of the adults were also using CGMs, but just 6% of the children and 18% of the adults had prior experience with AID systems.

Baseline A1c in children was 7.5% and in adults was 7.7%.

After a 4-week run-in, all patients were randomized to the open-source AID or insulin pump plus CGM for 6 months.

The final group analyzed consisted of 42 patients in the open-source AID group and 53 patients in the comparator group.

The primary outcome, the adjusted mean difference in percent time-in-range (glucose of 70-180 mg/dL) during the final 2 weeks of the 6-month trial, showed a significant difference of 14% (P < .001) with open-source AID compared with pump plus CGM only.

Time-in-range in the open-source AID group rose from 61.2% to 71.2%, while it actually dropped slightly in the comparator group, from 57.7% to 54.5%.

The proportion of patients achieving time-in-range greater than 70% with open-source AID was 60% versus just 15% with pump plus CGM.

Glycemic improvements with open-source AID were significant for adults and children and were greater for those with higher baseline A1c levels. The effect was immediate and sustained throughout the study period, “which is super-pleasing, because there was a worry that the technical burden of open source might be [leading to] dropout, but we didn’t see that. It was sustained right through to the end of the trial,” Dr. de Bock commented.

Hypoglycemic rates didn’t differ between groups, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis.
 

No more waiting: What is the future of open-source AID?

When the open-source APS was first developed, users coined the motto: “We are not waiting.” But now that the “wait” is over and several commercial AIDs have been approved by regulatory bodies, with others still in the pipeline, will people still use open-source systems?

There are no current data on people moving from DIY to commercial systems. However, Dr. de Bock said, “For most who undertook an open-source option, the precision of the settings that they can use and enjoy would mean that most would likely stick to their open source.”

Dr. Isaacs agrees: “I actually don’t think it’s going to go away in the near future, because the FDA has very specific criteria for where these [formally approved] devices can be in terms of their target ranges and requirements versus with open source you can really customize. So I still think there’s going to be a subset of people who want that customization, who want the lower targets.”

Dana Lewis, the originator of the DIY system and a CREATE coauthor, told this news organization: “I don’t believe there has been a fall-off, and in fact, I think open-source AID has continued to have ongoing uptake as awareness increases about options and as more pumps and CGMs become interoperable with various open-source AID choices.”

“I think uptake increasing is also influenced by the fact that in places like Europe, Asia, and Australia there are in-warranty on-the-market pumps that are compatible and interoperable with open-source AID. I think awareness of AID overall increases uptake of commercial and open source alike,” she said.

“Clinicians, as emphasized in recent position statements, must maintain support of the person with diabetes, irrespective of the mode of treatment they are on. ... Health care providers should be encouraged to learn from the experiences of the people who have stuck with open-source AID or switched, so that they can inform themselves of the relative strengths and benefits of each system,” Dr. de Bock advised.

Ms. Lewis noted: “We are seeing increasing awareness and comfort in endocrinologists from the community perspective, and we do hope that this study helps increase conversation and awareness of the safety and efficacy of open-source AID systems as an option for people with diabetes.”

In fact, the team published an article specifically about clinicians’ experience in CREATE. “The learning curve is similar across AID technology,” she observed.  

Findings of a 6-month continuation phase of CREATE, in which all participants used the open-source AID, are scheduled to be presented in September at the European Association for the Study of Diabetes annual meeting.

The study was funded by the Health Research Council of New Zealand, with hardware support from SOOIL Developments, South Korea; Dexcom; and Vodafone New Zealand. Dr. de Bock has reported receiving honoraria and/or research funding from Novo Nordisk, Sanofi, Pfizer, Medtronic, Lilly, Ypsomed, and Dexcom. Dr. Isaacs has reported serving as a consultant for LifeScan, Lilly, and Insulet, and as a speaker for Dexcom, Medtronic, Abbott, and Novo Nordisk. Ms. Lewis has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Avexitide (Eiger Biopharmaceuticals), a first-in-class glucagonlike peptide (GLP)–1 receptor blocker, significantly reduced hypoglycemia in patients with refractory postbariatric hypoglycemia, new research finds.  

Postbariatric hypoglycemia is a complication of bariatric surgery that is estimated to occur in about 29%-34% of people who undergo Roux-en-Y gastric bypass and in 11%-23% of those who undergo vertical sleeve gastrectomy. It typically manifests about 1-3 hours after meals and can lead to severe neuroglycopenic symptoms including blurred vision, confusion, drowsiness, and incoordination.

In addition, more than one-third (37%) with the condition have hypoglycemic unawareness. This can lead to seizures in about 59%, loss of consciousness and hospitalization in 50%, motor vehicle accidents, and even death. More than 90% with the condition consider themselves disabled, and 41% report being unable to work.

There are no currently approved medical treatments for postbariatric hypoglycemia. The standard of care is medical nutrition therapy involving a low-carbohydrate diet with carb restriction and small, frequent mixed meals. If this doesn’t work, off-label stepped pharmacotherapy has been tried, including acarbose (Precose), octreotide (Sandostatin), and diazoxide (Proglycem).

But “these are limited by efficacy and tolerability,” said Marilyn Tan, MD, who presented the findings from the phase 2 trial of avexitide at the annual meeting of the Endocrine Society.

In very severe cases, gastrostomy tubes or bypass reversal are options but those lead to weight regain and incomplete efficacy. “Safe, effective, and targeted therapies are needed urgently for postbariatric hypoglycemia,” said Dr. Tan, of the department of endocrinology at Stanford (Calif.) University.

The pathophysiology isn’t fully understood, but there appears to be an exaggerated GLP-1 response that leads to abnormal insulin secretion and symptomatic hyperinsulinemic hypoglycemia. Avexitide (formerly exendin 9-39), blocks the GLP-1 receptor and mitigates the excessive GLP-1 response, she explained.

Asked to comment, session moderator Michelle Van Name, MD, told this news organization, “This is a problem and it’s important for us to understand more about it and to identify different treatment options so these patients can continue to live their full, healthy lives post bariatric surgery.”

And, avexitide also holds potential for treating congenital hyperinsulinism, “which is a very challenging disease to treat in babies,” noted Dr. Van Name, a pediatric endocrinologist at Yale University, New Haven, Conn.
 

Drug reduced all levels of hypoglycemia, across surgery types

The study enrolled 14 women and 2 men with severe refractory postbariatric surgery hypoglycemia despite medical nutrition therapy. A majority (9) had undergone Roux-en-Y gastric bypass, 4 had vertical sleeve gastrectomy, 2 gastrectomy, and 1 had Nissen fundoplication. Seven patients (43.7%) had experienced loss of consciousness from hyperinsulinemic hypoglycemia. None had diabetes.

They were randomly assigned to either subcutaneous 45 mg of avexitide twice daily or 90 mg once daily for 14 days each, with a 2-day washout period followed by a switch to the other dose.

Both doses resulted in significant reductions in hypoglycemia as measured by self–blood glucose monitoring. The once-daily dose reduced level 1 hypoglycemia (glucose < 70 mg/dL) by 67.5% and it reduced level 2 (< 54 mg/dL) by 53.3% (P = .0043).

Even greater reductions were seen in severe hypoglycemia (that is, altered mental status/requiring assistance) – by 67.5% for the twice-daily dose (P = .0003) and by 66.1% with the once-daily dose (P = .0003). 

“This is consistent with what we’ve seen in prior avexitide trials,” Dr. Tan noted.

More hypoglycemic events were captured using blinded continuous glucose monitoring (CGM), since it picked up episodes of which the patient was unaware. There were significant reductions in percentage time spent in level 1 and level 2 hypoglycemia, as well as in absolute number of hypoglycemic events over 14 days.

Here, the effect was greater with the once-daily 90 mg dose, with reductions of up to 65% in time spent and number of events, but results for the twice-daily dose were also significant, Dr. Tan said.

The drug was effective across all surgical subtypes. Patients who underwent vertical sleeve gastrectomy/gastrectomy had greater rates of hypoglycemia at baseline and “robust responses to avexitide subcutaneous injections. This supports the critical role of GLP-1,” Dr. Tan said.

There were no severe adverse events. The most commonly reported adverse events were diarrhea, headache, bloating, and injection-site reaction/bruising. All were mild and self-limited and resolved without treatment. No participants withdrew from the study.

Eiger Biopharmaceuticals is currently working with the U.S. Food and Drug Administration and the European Medicines Agency to design a phase 3 trial.

The study is an investor-initiated trial with funding from Eiger Biopharmaceuticals. Dr. Tan receives research support from Eiger Biopharmaceuticals as a site investigator. Dr. Van Name is an investigator for a trial sponsored by Provention Bio.

A version of this article first appeared on Medscape.com.

Avexitide (Eiger Biopharmaceuticals), a first-in-class glucagonlike peptide (GLP)–1 receptor blocker, significantly reduced hypoglycemia in patients with refractory postbariatric hypoglycemia, new research finds.  

Postbariatric hypoglycemia is a complication of bariatric surgery that is estimated to occur in about 29%-34% of people who undergo Roux-en-Y gastric bypass and in 11%-23% of those who undergo vertical sleeve gastrectomy. It typically manifests about 1-3 hours after meals and can lead to severe neuroglycopenic symptoms including blurred vision, confusion, drowsiness, and incoordination.

In addition, more than one-third (37%) with the condition have hypoglycemic unawareness. This can lead to seizures in about 59%, loss of consciousness and hospitalization in 50%, motor vehicle accidents, and even death. More than 90% with the condition consider themselves disabled, and 41% report being unable to work.

There are no currently approved medical treatments for postbariatric hypoglycemia. The standard of care is medical nutrition therapy involving a low-carbohydrate diet with carb restriction and small, frequent mixed meals. If this doesn’t work, off-label stepped pharmacotherapy has been tried, including acarbose (Precose), octreotide (Sandostatin), and diazoxide (Proglycem).

But “these are limited by efficacy and tolerability,” said Marilyn Tan, MD, who presented the findings from the phase 2 trial of avexitide at the annual meeting of the Endocrine Society.

In very severe cases, gastrostomy tubes or bypass reversal are options but those lead to weight regain and incomplete efficacy. “Safe, effective, and targeted therapies are needed urgently for postbariatric hypoglycemia,” said Dr. Tan, of the department of endocrinology at Stanford (Calif.) University.

The pathophysiology isn’t fully understood, but there appears to be an exaggerated GLP-1 response that leads to abnormal insulin secretion and symptomatic hyperinsulinemic hypoglycemia. Avexitide (formerly exendin 9-39), blocks the GLP-1 receptor and mitigates the excessive GLP-1 response, she explained.

Asked to comment, session moderator Michelle Van Name, MD, told this news organization, “This is a problem and it’s important for us to understand more about it and to identify different treatment options so these patients can continue to live their full, healthy lives post bariatric surgery.”

And, avexitide also holds potential for treating congenital hyperinsulinism, “which is a very challenging disease to treat in babies,” noted Dr. Van Name, a pediatric endocrinologist at Yale University, New Haven, Conn.
 

Drug reduced all levels of hypoglycemia, across surgery types

The study enrolled 14 women and 2 men with severe refractory postbariatric surgery hypoglycemia despite medical nutrition therapy. A majority (9) had undergone Roux-en-Y gastric bypass, 4 had vertical sleeve gastrectomy, 2 gastrectomy, and 1 had Nissen fundoplication. Seven patients (43.7%) had experienced loss of consciousness from hyperinsulinemic hypoglycemia. None had diabetes.

They were randomly assigned to either subcutaneous 45 mg of avexitide twice daily or 90 mg once daily for 14 days each, with a 2-day washout period followed by a switch to the other dose.

Both doses resulted in significant reductions in hypoglycemia as measured by self–blood glucose monitoring. The once-daily dose reduced level 1 hypoglycemia (glucose < 70 mg/dL) by 67.5% and it reduced level 2 (< 54 mg/dL) by 53.3% (P = .0043).

Even greater reductions were seen in severe hypoglycemia (that is, altered mental status/requiring assistance) – by 67.5% for the twice-daily dose (P = .0003) and by 66.1% with the once-daily dose (P = .0003). 

“This is consistent with what we’ve seen in prior avexitide trials,” Dr. Tan noted.

More hypoglycemic events were captured using blinded continuous glucose monitoring (CGM), since it picked up episodes of which the patient was unaware. There were significant reductions in percentage time spent in level 1 and level 2 hypoglycemia, as well as in absolute number of hypoglycemic events over 14 days.

Here, the effect was greater with the once-daily 90 mg dose, with reductions of up to 65% in time spent and number of events, but results for the twice-daily dose were also significant, Dr. Tan said.

The drug was effective across all surgical subtypes. Patients who underwent vertical sleeve gastrectomy/gastrectomy had greater rates of hypoglycemia at baseline and “robust responses to avexitide subcutaneous injections. This supports the critical role of GLP-1,” Dr. Tan said.

There were no severe adverse events. The most commonly reported adverse events were diarrhea, headache, bloating, and injection-site reaction/bruising. All were mild and self-limited and resolved without treatment. No participants withdrew from the study.

Eiger Biopharmaceuticals is currently working with the U.S. Food and Drug Administration and the European Medicines Agency to design a phase 3 trial.

The study is an investor-initiated trial with funding from Eiger Biopharmaceuticals. Dr. Tan receives research support from Eiger Biopharmaceuticals as a site investigator. Dr. Van Name is an investigator for a trial sponsored by Provention Bio.

A version of this article first appeared on Medscape.com.

Avexitide (Eiger Biopharmaceuticals), a first-in-class glucagonlike peptide (GLP)–1 receptor blocker, significantly reduced hypoglycemia in patients with refractory postbariatric hypoglycemia, new research finds.  

Postbariatric hypoglycemia is a complication of bariatric surgery that is estimated to occur in about 29%-34% of people who undergo Roux-en-Y gastric bypass and in 11%-23% of those who undergo vertical sleeve gastrectomy. It typically manifests about 1-3 hours after meals and can lead to severe neuroglycopenic symptoms including blurred vision, confusion, drowsiness, and incoordination.

In addition, more than one-third (37%) with the condition have hypoglycemic unawareness. This can lead to seizures in about 59%, loss of consciousness and hospitalization in 50%, motor vehicle accidents, and even death. More than 90% with the condition consider themselves disabled, and 41% report being unable to work.

There are no currently approved medical treatments for postbariatric hypoglycemia. The standard of care is medical nutrition therapy involving a low-carbohydrate diet with carb restriction and small, frequent mixed meals. If this doesn’t work, off-label stepped pharmacotherapy has been tried, including acarbose (Precose), octreotide (Sandostatin), and diazoxide (Proglycem).

But “these are limited by efficacy and tolerability,” said Marilyn Tan, MD, who presented the findings from the phase 2 trial of avexitide at the annual meeting of the Endocrine Society.

In very severe cases, gastrostomy tubes or bypass reversal are options but those lead to weight regain and incomplete efficacy. “Safe, effective, and targeted therapies are needed urgently for postbariatric hypoglycemia,” said Dr. Tan, of the department of endocrinology at Stanford (Calif.) University.

The pathophysiology isn’t fully understood, but there appears to be an exaggerated GLP-1 response that leads to abnormal insulin secretion and symptomatic hyperinsulinemic hypoglycemia. Avexitide (formerly exendin 9-39), blocks the GLP-1 receptor and mitigates the excessive GLP-1 response, she explained.

Asked to comment, session moderator Michelle Van Name, MD, told this news organization, “This is a problem and it’s important for us to understand more about it and to identify different treatment options so these patients can continue to live their full, healthy lives post bariatric surgery.”

And, avexitide also holds potential for treating congenital hyperinsulinism, “which is a very challenging disease to treat in babies,” noted Dr. Van Name, a pediatric endocrinologist at Yale University, New Haven, Conn.
 

Drug reduced all levels of hypoglycemia, across surgery types

The study enrolled 14 women and 2 men with severe refractory postbariatric surgery hypoglycemia despite medical nutrition therapy. A majority (9) had undergone Roux-en-Y gastric bypass, 4 had vertical sleeve gastrectomy, 2 gastrectomy, and 1 had Nissen fundoplication. Seven patients (43.7%) had experienced loss of consciousness from hyperinsulinemic hypoglycemia. None had diabetes.

They were randomly assigned to either subcutaneous 45 mg of avexitide twice daily or 90 mg once daily for 14 days each, with a 2-day washout period followed by a switch to the other dose.

Both doses resulted in significant reductions in hypoglycemia as measured by self–blood glucose monitoring. The once-daily dose reduced level 1 hypoglycemia (glucose < 70 mg/dL) by 67.5% and it reduced level 2 (< 54 mg/dL) by 53.3% (P = .0043).

Even greater reductions were seen in severe hypoglycemia (that is, altered mental status/requiring assistance) – by 67.5% for the twice-daily dose (P = .0003) and by 66.1% with the once-daily dose (P = .0003). 

“This is consistent with what we’ve seen in prior avexitide trials,” Dr. Tan noted.

More hypoglycemic events were captured using blinded continuous glucose monitoring (CGM), since it picked up episodes of which the patient was unaware. There were significant reductions in percentage time spent in level 1 and level 2 hypoglycemia, as well as in absolute number of hypoglycemic events over 14 days.

Here, the effect was greater with the once-daily 90 mg dose, with reductions of up to 65% in time spent and number of events, but results for the twice-daily dose were also significant, Dr. Tan said.

The drug was effective across all surgical subtypes. Patients who underwent vertical sleeve gastrectomy/gastrectomy had greater rates of hypoglycemia at baseline and “robust responses to avexitide subcutaneous injections. This supports the critical role of GLP-1,” Dr. Tan said.

There were no severe adverse events. The most commonly reported adverse events were diarrhea, headache, bloating, and injection-site reaction/bruising. All were mild and self-limited and resolved without treatment. No participants withdrew from the study.

Eiger Biopharmaceuticals is currently working with the U.S. Food and Drug Administration and the European Medicines Agency to design a phase 3 trial.

The study is an investor-initiated trial with funding from Eiger Biopharmaceuticals. Dr. Tan receives research support from Eiger Biopharmaceuticals as a site investigator. Dr. Van Name is an investigator for a trial sponsored by Provention Bio.

A version of this article first appeared on Medscape.com.