Miriam E. Tucker

Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors does not appear to raise the risk for fractures in older adults, new research suggests.

The data come from a nationwide propensity score-matched study of U.S. Medicare recipients with type 2 diabetes who were new users of either an SGLT2 inhibitor, a dipeptidyl peptidase 4 (DPP-4) inhibitor, or a glucagon-like peptide (GLP-1) receptor agonist.

“The use of SGLT2 inhibitors was not associated with an increased risk of nontraumatic fractures compared with DPP-4 inhibitors or GLP-1 agonists. Results were consistent across categories of sex, frailty, age, and insulin use,” say Min Zhuo, MD, of Harvard Medical School, Boston, and colleagues, who published their work online October 27 in JAMA Network Open.

“Our results add to the evidence base evaluating the safety profile of SGLT2 inhibitors in older adults outside of [randomized controlled trials] and further characterize the risk-benefit balance of SGLT2 inhibitors in clinical practice,” they write.

Asked to comment, Simeon I. Taylor, MD, PhD, told this news organization, “This is a high-quality study that is generally reassuring that relatively short, less than 1 year, treatment with an SGLT2 inhibitor does not appear to significantly increase the risk of bone fractures.”

However, Dr. Taylor, of the Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, also noted: “Notwithstanding these reassuring data, the paper also does a good job of pointing out important limitations.”

“Most importantly, these data do not address questions related to the risk of long-term chronic therapy. It is instructive to refer back to the published data demonstrating an approximately 2-year lag before a significant increase in the risk of fracture was observed in rosiglitazone-treated patients in the ADOPT study. The length of the lag is likely related to the baseline bone mineral density at the time drug therapy is initiated. These considerations may contribute to the observed variation in bone-related outcomes in different studies.”

Concern about SGLT2 inhibitors and fractures first arose in 2017 from the CANVAS study, in which the overall fracture risk with canagliflozin was a significant 26% higher than placebo. However, subsequent larger randomized trials of canagliflozin and other SGLT2 inhibitors did not find the same risk.

In addition, previous observational studies in younger adults have also not found use of SGLT2 inhibitors to be associated with increased fracture risk compared with DPP-4 inhibitors or GLP-1 agonists.
 

Understanding fracture risk with SGLT2 inhibitors is ‘critical’

Older adults with type 2 diabetes may benefit from reductions in atherosclerotic cardiovascular events, hospitalization for heart failure, end-stage kidney disease, and death associated with SGLT2 inhibitors, but the fact that aging may have negative effects on bone metabolism means “understanding the fracture risk associated with SGLT2 inhibitors in older adults with type 2 diabetes is critical,” say Dr. Zhuo and colleagues.

In the current study, they analyzed claims data for Medicare beneficiaries aged 66 years and older (1 year past Medicare eligibility) who were newly prescribed an SGLT2 inhibitor, DPP-4 inhibitor, or GLP-1 agonist between April 1, 2013 and Dec. 31, 2017.

A total of 45,889 patients from each treatment group were propensity-matched using 58 baseline characteristics, for a total of 137,667 patients.

After matching, there were 501 events of the primary composite outcome (nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention) within 30 days. By treatment group, fracture rates per 1,000 person-years were 4.69, 5.26, and 4.71 for SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 agonists respectively.

The differences between patients taking DPP-4 inhibitors or GLP-1 agonists compared with SGLT2 inhibitors were not significant, with hazard ratios of 0.90 and 1.00, respectively.     

Results remained consistent in various sensitivity and subgroup analyses, including limiting the data to just the canagliflozin group. Overall, the fracture rate was greater with female sex, frailty, older age, and insulin use, consistent across drug classes.

The risks for falls and hypoglycemia were lower in the SGLT2 inhibitor versus matched DPP-4 inhibitor groups (hazard ratio, 0.82), and there was no difference in syncope. None of those differences were significant for the SGLT2 inhibitor group compared with the GLP-1 agonist group.

Consistent with previous data, the risk for diabetic ketoacidosis was higher with SGLT2 inhibitors versus DPP-4 inhibitors and GLP-1 agonists (HR, 1.29 and 1.58), and the risk for heart failure hospitalization was lower (HR, 0.42 and 0.69).

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, Harvard Medical School. Dr. Zhuo was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors does not appear to raise the risk for fractures in older adults, new research suggests.

The data come from a nationwide propensity score-matched study of U.S. Medicare recipients with type 2 diabetes who were new users of either an SGLT2 inhibitor, a dipeptidyl peptidase 4 (DPP-4) inhibitor, or a glucagon-like peptide (GLP-1) receptor agonist.

“The use of SGLT2 inhibitors was not associated with an increased risk of nontraumatic fractures compared with DPP-4 inhibitors or GLP-1 agonists. Results were consistent across categories of sex, frailty, age, and insulin use,” say Min Zhuo, MD, of Harvard Medical School, Boston, and colleagues, who published their work online October 27 in JAMA Network Open.

“Our results add to the evidence base evaluating the safety profile of SGLT2 inhibitors in older adults outside of [randomized controlled trials] and further characterize the risk-benefit balance of SGLT2 inhibitors in clinical practice,” they write.

Asked to comment, Simeon I. Taylor, MD, PhD, told this news organization, “This is a high-quality study that is generally reassuring that relatively short, less than 1 year, treatment with an SGLT2 inhibitor does not appear to significantly increase the risk of bone fractures.”

However, Dr. Taylor, of the Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, also noted: “Notwithstanding these reassuring data, the paper also does a good job of pointing out important limitations.”

“Most importantly, these data do not address questions related to the risk of long-term chronic therapy. It is instructive to refer back to the published data demonstrating an approximately 2-year lag before a significant increase in the risk of fracture was observed in rosiglitazone-treated patients in the ADOPT study. The length of the lag is likely related to the baseline bone mineral density at the time drug therapy is initiated. These considerations may contribute to the observed variation in bone-related outcomes in different studies.”

Concern about SGLT2 inhibitors and fractures first arose in 2017 from the CANVAS study, in which the overall fracture risk with canagliflozin was a significant 26% higher than placebo. However, subsequent larger randomized trials of canagliflozin and other SGLT2 inhibitors did not find the same risk.

In addition, previous observational studies in younger adults have also not found use of SGLT2 inhibitors to be associated with increased fracture risk compared with DPP-4 inhibitors or GLP-1 agonists.
 

Understanding fracture risk with SGLT2 inhibitors is ‘critical’

Older adults with type 2 diabetes may benefit from reductions in atherosclerotic cardiovascular events, hospitalization for heart failure, end-stage kidney disease, and death associated with SGLT2 inhibitors, but the fact that aging may have negative effects on bone metabolism means “understanding the fracture risk associated with SGLT2 inhibitors in older adults with type 2 diabetes is critical,” say Dr. Zhuo and colleagues.

In the current study, they analyzed claims data for Medicare beneficiaries aged 66 years and older (1 year past Medicare eligibility) who were newly prescribed an SGLT2 inhibitor, DPP-4 inhibitor, or GLP-1 agonist between April 1, 2013 and Dec. 31, 2017.

A total of 45,889 patients from each treatment group were propensity-matched using 58 baseline characteristics, for a total of 137,667 patients.

After matching, there were 501 events of the primary composite outcome (nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention) within 30 days. By treatment group, fracture rates per 1,000 person-years were 4.69, 5.26, and 4.71 for SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 agonists respectively.

The differences between patients taking DPP-4 inhibitors or GLP-1 agonists compared with SGLT2 inhibitors were not significant, with hazard ratios of 0.90 and 1.00, respectively.     

Results remained consistent in various sensitivity and subgroup analyses, including limiting the data to just the canagliflozin group. Overall, the fracture rate was greater with female sex, frailty, older age, and insulin use, consistent across drug classes.

The risks for falls and hypoglycemia were lower in the SGLT2 inhibitor versus matched DPP-4 inhibitor groups (hazard ratio, 0.82), and there was no difference in syncope. None of those differences were significant for the SGLT2 inhibitor group compared with the GLP-1 agonist group.

Consistent with previous data, the risk for diabetic ketoacidosis was higher with SGLT2 inhibitors versus DPP-4 inhibitors and GLP-1 agonists (HR, 1.29 and 1.58), and the risk for heart failure hospitalization was lower (HR, 0.42 and 0.69).

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, Harvard Medical School. Dr. Zhuo was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors does not appear to raise the risk for fractures in older adults, new research suggests.

The data come from a nationwide propensity score-matched study of U.S. Medicare recipients with type 2 diabetes who were new users of either an SGLT2 inhibitor, a dipeptidyl peptidase 4 (DPP-4) inhibitor, or a glucagon-like peptide (GLP-1) receptor agonist.

“The use of SGLT2 inhibitors was not associated with an increased risk of nontraumatic fractures compared with DPP-4 inhibitors or GLP-1 agonists. Results were consistent across categories of sex, frailty, age, and insulin use,” say Min Zhuo, MD, of Harvard Medical School, Boston, and colleagues, who published their work online October 27 in JAMA Network Open.

“Our results add to the evidence base evaluating the safety profile of SGLT2 inhibitors in older adults outside of [randomized controlled trials] and further characterize the risk-benefit balance of SGLT2 inhibitors in clinical practice,” they write.

Asked to comment, Simeon I. Taylor, MD, PhD, told this news organization, “This is a high-quality study that is generally reassuring that relatively short, less than 1 year, treatment with an SGLT2 inhibitor does not appear to significantly increase the risk of bone fractures.”

However, Dr. Taylor, of the Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, also noted: “Notwithstanding these reassuring data, the paper also does a good job of pointing out important limitations.”

“Most importantly, these data do not address questions related to the risk of long-term chronic therapy. It is instructive to refer back to the published data demonstrating an approximately 2-year lag before a significant increase in the risk of fracture was observed in rosiglitazone-treated patients in the ADOPT study. The length of the lag is likely related to the baseline bone mineral density at the time drug therapy is initiated. These considerations may contribute to the observed variation in bone-related outcomes in different studies.”

Concern about SGLT2 inhibitors and fractures first arose in 2017 from the CANVAS study, in which the overall fracture risk with canagliflozin was a significant 26% higher than placebo. However, subsequent larger randomized trials of canagliflozin and other SGLT2 inhibitors did not find the same risk.

In addition, previous observational studies in younger adults have also not found use of SGLT2 inhibitors to be associated with increased fracture risk compared with DPP-4 inhibitors or GLP-1 agonists.
 

Understanding fracture risk with SGLT2 inhibitors is ‘critical’

Older adults with type 2 diabetes may benefit from reductions in atherosclerotic cardiovascular events, hospitalization for heart failure, end-stage kidney disease, and death associated with SGLT2 inhibitors, but the fact that aging may have negative effects on bone metabolism means “understanding the fracture risk associated with SGLT2 inhibitors in older adults with type 2 diabetes is critical,” say Dr. Zhuo and colleagues.

In the current study, they analyzed claims data for Medicare beneficiaries aged 66 years and older (1 year past Medicare eligibility) who were newly prescribed an SGLT2 inhibitor, DPP-4 inhibitor, or GLP-1 agonist between April 1, 2013 and Dec. 31, 2017.

A total of 45,889 patients from each treatment group were propensity-matched using 58 baseline characteristics, for a total of 137,667 patients.

After matching, there were 501 events of the primary composite outcome (nontraumatic pelvic fracture, hip fracture requiring surgery, or humerus, radius, or ulna fracture requiring intervention) within 30 days. By treatment group, fracture rates per 1,000 person-years were 4.69, 5.26, and 4.71 for SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 agonists respectively.

The differences between patients taking DPP-4 inhibitors or GLP-1 agonists compared with SGLT2 inhibitors were not significant, with hazard ratios of 0.90 and 1.00, respectively.     

Results remained consistent in various sensitivity and subgroup analyses, including limiting the data to just the canagliflozin group. Overall, the fracture rate was greater with female sex, frailty, older age, and insulin use, consistent across drug classes.

The risks for falls and hypoglycemia were lower in the SGLT2 inhibitor versus matched DPP-4 inhibitor groups (hazard ratio, 0.82), and there was no difference in syncope. None of those differences were significant for the SGLT2 inhibitor group compared with the GLP-1 agonist group.

Consistent with previous data, the risk for diabetic ketoacidosis was higher with SGLT2 inhibitors versus DPP-4 inhibitors and GLP-1 agonists (HR, 1.29 and 1.58), and the risk for heart failure hospitalization was lower (HR, 0.42 and 0.69).

The study was funded by the Division of Pharmacoepidemiology and Pharmacoeconomics, department of medicine, Brigham and Women’s Hospital, Harvard Medical School. Dr. Zhuo was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Taylor is a consultant for Ionis Pharmaceuticals.

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

Low androgen levels appear to be linked to the development of posttransplantation diabetes mellitus (PTDM) in male kidney transplant recipients, new research suggests.

London_England/Thinkstock

Among 243 men who did not have diabetes prior to undergoing kidney transplantation, levels of both dihydrotestosterone (DHT) and testosterone were inversely related to the risk for developing diabetes the next 5 years.

“These results suggest that androgen insufficiency could play a role in the frequent deterioration of the glucose metabolism after kidney transplantation,” Suzanne P. Stam and colleagues wrote in Diabetes Care.

However, “our study has unfortunately no direct clinical findings as it was of an observational nature,” Ms. Stam told this news organization. “As a result, we can say that we have observed an association and have not established a causal relationship. So based on our study alone there is not a reason to start screening for low androgen values.”

Previous data have suggested that failure of pancreatic beta cell secretion of insulin plays a role in PTDM. In addition, DHT appears to act on the androgen receptor in pancreatic beta cells to enhance insulin secretion, while testosterone deficiency has been shown to play a role in the development of type 2 diabetes in aging males and in men receiving androgen-deprivation therapy. And, randomized clinical trials have found favorable metabolic effects of testosterone replacement therapy in hypogonadal men with type 2 diabetes.

The current post hoc analysis of a prospective single-center cohort study is the first longitudinal epidemiological investigation of the role of androgens in PTDM in kidney transplant recipients. The subjects, all men, had functioning grafts for at least a year posttransplantation. Androgen levels were assessed by liquid chromatography–tandem mass spectrometry.

At a median follow-up duration of 5.3 years, 28 (11.5%) of the men had developed PTDM. By DHT tertile, the proportions developing diabetes were 19% (15) for the lowest, 12% (10) for the middle, and 4% (3) for men with the highest DHT tertile (P = .008). A similar relationship was seen with tertiles of testosterone, with 17% (14), 14% (11), and 4% (3) developing diabetes in the lowest, middle, and highest tertiles, respectively (P = .01).

In unadjusted analysis, every doubling of DHT was linked to a 27% increased risk for PTDM (P < .001). The association remained significant after adjustments for age, estimated glomerular filtration rate, time between transplantation and baseline, body mass index, high sensitivity C-reactive protein, medication use, and baseline hemoglobin A1c (all P < .001). Similar results were found with total testosterone.

Ms. Stam, of the division of nephrology at the University Medical Center Groningen, the Netherlands, noted in an interview that, in the Netherlands, about 15% of those with kidney failure have preexisting diabetes, compared with about 50% in other western countries, including the United States.

She said that her team is currently working on a study to investigate the association between androgens and the development of PTDM in female kidney transplant recipients.

The study was funded by the TransplantLines Food and Nutrition Biobank and Cohort Study, Top Institute Food and Nutrition, and partly by the European Union’s Horizon 2020 research and innovation program. Ms. Stam and the other authors have no further disclosures.

Low androgen levels appear to be linked to the development of posttransplantation diabetes mellitus (PTDM) in male kidney transplant recipients, new research suggests.

London_England/Thinkstock

Among 243 men who did not have diabetes prior to undergoing kidney transplantation, levels of both dihydrotestosterone (DHT) and testosterone were inversely related to the risk for developing diabetes the next 5 years.

“These results suggest that androgen insufficiency could play a role in the frequent deterioration of the glucose metabolism after kidney transplantation,” Suzanne P. Stam and colleagues wrote in Diabetes Care.

However, “our study has unfortunately no direct clinical findings as it was of an observational nature,” Ms. Stam told this news organization. “As a result, we can say that we have observed an association and have not established a causal relationship. So based on our study alone there is not a reason to start screening for low androgen values.”

Previous data have suggested that failure of pancreatic beta cell secretion of insulin plays a role in PTDM. In addition, DHT appears to act on the androgen receptor in pancreatic beta cells to enhance insulin secretion, while testosterone deficiency has been shown to play a role in the development of type 2 diabetes in aging males and in men receiving androgen-deprivation therapy. And, randomized clinical trials have found favorable metabolic effects of testosterone replacement therapy in hypogonadal men with type 2 diabetes.

The current post hoc analysis of a prospective single-center cohort study is the first longitudinal epidemiological investigation of the role of androgens in PTDM in kidney transplant recipients. The subjects, all men, had functioning grafts for at least a year posttransplantation. Androgen levels were assessed by liquid chromatography–tandem mass spectrometry.

At a median follow-up duration of 5.3 years, 28 (11.5%) of the men had developed PTDM. By DHT tertile, the proportions developing diabetes were 19% (15) for the lowest, 12% (10) for the middle, and 4% (3) for men with the highest DHT tertile (P = .008). A similar relationship was seen with tertiles of testosterone, with 17% (14), 14% (11), and 4% (3) developing diabetes in the lowest, middle, and highest tertiles, respectively (P = .01).

In unadjusted analysis, every doubling of DHT was linked to a 27% increased risk for PTDM (P < .001). The association remained significant after adjustments for age, estimated glomerular filtration rate, time between transplantation and baseline, body mass index, high sensitivity C-reactive protein, medication use, and baseline hemoglobin A1c (all P < .001). Similar results were found with total testosterone.

Ms. Stam, of the division of nephrology at the University Medical Center Groningen, the Netherlands, noted in an interview that, in the Netherlands, about 15% of those with kidney failure have preexisting diabetes, compared with about 50% in other western countries, including the United States.

She said that her team is currently working on a study to investigate the association between androgens and the development of PTDM in female kidney transplant recipients.

The study was funded by the TransplantLines Food and Nutrition Biobank and Cohort Study, Top Institute Food and Nutrition, and partly by the European Union’s Horizon 2020 research and innovation program. Ms. Stam and the other authors have no further disclosures.

Low androgen levels appear to be linked to the development of posttransplantation diabetes mellitus (PTDM) in male kidney transplant recipients, new research suggests.

London_England/Thinkstock

Among 243 men who did not have diabetes prior to undergoing kidney transplantation, levels of both dihydrotestosterone (DHT) and testosterone were inversely related to the risk for developing diabetes the next 5 years.

“These results suggest that androgen insufficiency could play a role in the frequent deterioration of the glucose metabolism after kidney transplantation,” Suzanne P. Stam and colleagues wrote in Diabetes Care.

However, “our study has unfortunately no direct clinical findings as it was of an observational nature,” Ms. Stam told this news organization. “As a result, we can say that we have observed an association and have not established a causal relationship. So based on our study alone there is not a reason to start screening for low androgen values.”

Previous data have suggested that failure of pancreatic beta cell secretion of insulin plays a role in PTDM. In addition, DHT appears to act on the androgen receptor in pancreatic beta cells to enhance insulin secretion, while testosterone deficiency has been shown to play a role in the development of type 2 diabetes in aging males and in men receiving androgen-deprivation therapy. And, randomized clinical trials have found favorable metabolic effects of testosterone replacement therapy in hypogonadal men with type 2 diabetes.

The current post hoc analysis of a prospective single-center cohort study is the first longitudinal epidemiological investigation of the role of androgens in PTDM in kidney transplant recipients. The subjects, all men, had functioning grafts for at least a year posttransplantation. Androgen levels were assessed by liquid chromatography–tandem mass spectrometry.

At a median follow-up duration of 5.3 years, 28 (11.5%) of the men had developed PTDM. By DHT tertile, the proportions developing diabetes were 19% (15) for the lowest, 12% (10) for the middle, and 4% (3) for men with the highest DHT tertile (P = .008). A similar relationship was seen with tertiles of testosterone, with 17% (14), 14% (11), and 4% (3) developing diabetes in the lowest, middle, and highest tertiles, respectively (P = .01).

In unadjusted analysis, every doubling of DHT was linked to a 27% increased risk for PTDM (P < .001). The association remained significant after adjustments for age, estimated glomerular filtration rate, time between transplantation and baseline, body mass index, high sensitivity C-reactive protein, medication use, and baseline hemoglobin A1c (all P < .001). Similar results were found with total testosterone.

Ms. Stam, of the division of nephrology at the University Medical Center Groningen, the Netherlands, noted in an interview that, in the Netherlands, about 15% of those with kidney failure have preexisting diabetes, compared with about 50% in other western countries, including the United States.

She said that her team is currently working on a study to investigate the association between androgens and the development of PTDM in female kidney transplant recipients.

The study was funded by the TransplantLines Food and Nutrition Biobank and Cohort Study, Top Institute Food and Nutrition, and partly by the European Union’s Horizon 2020 research and innovation program. Ms. Stam and the other authors have no further disclosures.

Despite the extensive recent focus on its cost, insulin use in the United States remains dominated by insulin glargine and other analogs, as well as pen devices for delivery, new research shows.

The findings come from a nationally representative audit of outpatient care with input from nearly 5,000 physicians who prescribed insulin to patients with type 2 diabetes in 2016-2020.

The dramatic rise in the price of insulin in the United States has been extensively discussed in recent years, particularly with the newer analogs as compared with older human insulins.

Few studies indicate analog insulins better than human insulins

“Our findings suggest that even with increased public scrutiny for insulin products ... [the market is] dominated by the use of insulin analogs and insulin pen delivery devices, with persistent uptake of newer products as they are approved,” lead author Rita R. Kalyani, MD, told this news organization.

“Though newer insulins offer potentially greater flexibility with reduced hypoglycemia for many patients, they are also much more costly, with minimal to no head-to-head studies suggesting significant differences in glucose-lowering efficacy when compared to human insulins,” she stressed.

“We found it surprising that, despite the much-publicized concerns regarding insulin costs, analog insulins continue to represent more than 80% of insulin visits in the U.S.” added Dr. Kalyani, of the Division of Endocrinology, Diabetes & Metabolism at Johns Hopkins University School of Medicine, Baltimore.

However, as expected, the study also revealed a gradual increased uptake in the use of biosimilar insulins as more have been introduced to the market.

Dr. Kalyani advised, “Clinicians should be aware of their individual prescribing patterns for insulin and consider the affordability of insulin for patients as part of shared decision-making during clinic visits, particularly given the greater financial strain that many patients have faced during the ongoing COVID-19 pandemic and the rising societal costs for diabetes care.”

The research was published online October 12 in JAMA Network Open by Dr. Kalyani and colleagues.

Analogs prevailed, while biosimilar use rose

The data come from the Health National Disease and Therapeutic Index, a quarterly sampling of approximately 4,800 physicians that provides nationally representative diagnostic and prescribing information on patients treated by office-based physicians in the United States.

Overall, there were 27,860,691 insulin treatment visits for type 2 diabetes in 2016-2020. Of those, long-acting analog insulins (glargine [Lantus], detemir [Levemir], and degludec [Tresiba]) accounted for 67.3% of treatment visits in 2016 and 74.8% of treatment visits in 2020.

Rapid-acting insulin analogs (lispro [Humalog], aspart [Novolog], faster aspart [Fiasp], and glulisine [Apidra]) accounted for about 21.2% of visits in 2016 and about 16.5% in 2020.

On the other hand, intermediate- and short-acting human insulins (NPH and regular) accounted for just 3.7% of visits in 2016 and 2.6% in 2020.

Grouped together, the long- and short-acting analogs accounted for 92.7% of visits in 2016 and 86.3% in 2020, while the human insulins represented just 7.3% of visits in 2016 and 5.5% in 2020.

The biosimilar analog insulins (glargine and lispro) first appeared in the database in 2017, accounting for 2.6% of visits that year and 8.2% by 2020.

Overall, the number of visits for insulin treatment declined by 18% between 2016 and 2020, from 6.0 million to 4.9 million. That drop may be due to multiple factors, Dr. Kalyani said.

“Recently updated clinical practice guidelines from professional societies such as the American Diabetes Association recommend the use of glucagon-like peptide-1 (GLP-1) receptor agonists prior to insulin when injectable medications are being considered [for type 2 diabetes],” she noted.

“In addition, during the pandemic, patients may not have been seeing their health care providers for routine diabetes care as often as before ... These and other factors may have contributed to the decrease in insulin visits that we observed.”

By specific insulins, glargine has topped the list all along, accounting for about half of all treatment visits, at 52.6% in 2020. Degludec came in second, at 17.4%, and lispro third, at 9.5%.

Use of pen devices also increased

The proportion of treatment visits for insulin vials/syringes declined from 63.9% in 2016 to 41.1% in 2020, while visits for insulin pens rose from 36.1% to 58.7%.

“Many pens are more costly compared to vials of the same insulin product. Interestingly, some studies have found that use of insulin pens may promote greater patient adherence to insulin and, as a result, more broadly decrease health care costs associated with diabetes. However, we did not specifically investigate the cost of insulin in our study,” Dr. Kalyani noted.

The proportion of visits for “newer” insulins, defined as those approved in 2010 or later, rose from 18.1% in 2016 to 40.9% in 2020, while the concurrent drop for insulins approved prior to 2010 was from 81.9% to 59.1%.

“The findings of our study provide insight into potential drivers of insulin costs in the U.S. and may inform health policy,” the researchers conclude.

Funded in part by the National Heart, Lung, and Blood Institute. Dr. Kalyani currently serves on the Endocrinologic and Metabolic Drugs Advisory Committee of the U.S. Food and Drug Administration.

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

Despite the extensive recent focus on its cost, insulin use in the United States remains dominated by insulin glargine and other analogs, as well as pen devices for delivery, new research shows.

The findings come from a nationally representative audit of outpatient care with input from nearly 5,000 physicians who prescribed insulin to patients with type 2 diabetes in 2016-2020.

The dramatic rise in the price of insulin in the United States has been extensively discussed in recent years, particularly with the newer analogs as compared with older human insulins.

Few studies indicate analog insulins better than human insulins

“Our findings suggest that even with increased public scrutiny for insulin products ... [the market is] dominated by the use of insulin analogs and insulin pen delivery devices, with persistent uptake of newer products as they are approved,” lead author Rita R. Kalyani, MD, told this news organization.

“Though newer insulins offer potentially greater flexibility with reduced hypoglycemia for many patients, they are also much more costly, with minimal to no head-to-head studies suggesting significant differences in glucose-lowering efficacy when compared to human insulins,” she stressed.

“We found it surprising that, despite the much-publicized concerns regarding insulin costs, analog insulins continue to represent more than 80% of insulin visits in the U.S.” added Dr. Kalyani, of the Division of Endocrinology, Diabetes & Metabolism at Johns Hopkins University School of Medicine, Baltimore.

However, as expected, the study also revealed a gradual increased uptake in the use of biosimilar insulins as more have been introduced to the market.

Dr. Kalyani advised, “Clinicians should be aware of their individual prescribing patterns for insulin and consider the affordability of insulin for patients as part of shared decision-making during clinic visits, particularly given the greater financial strain that many patients have faced during the ongoing COVID-19 pandemic and the rising societal costs for diabetes care.”

The research was published online October 12 in JAMA Network Open by Dr. Kalyani and colleagues.

Analogs prevailed, while biosimilar use rose

The data come from the Health National Disease and Therapeutic Index, a quarterly sampling of approximately 4,800 physicians that provides nationally representative diagnostic and prescribing information on patients treated by office-based physicians in the United States.

Overall, there were 27,860,691 insulin treatment visits for type 2 diabetes in 2016-2020. Of those, long-acting analog insulins (glargine [Lantus], detemir [Levemir], and degludec [Tresiba]) accounted for 67.3% of treatment visits in 2016 and 74.8% of treatment visits in 2020.

Rapid-acting insulin analogs (lispro [Humalog], aspart [Novolog], faster aspart [Fiasp], and glulisine [Apidra]) accounted for about 21.2% of visits in 2016 and about 16.5% in 2020.

On the other hand, intermediate- and short-acting human insulins (NPH and regular) accounted for just 3.7% of visits in 2016 and 2.6% in 2020.

Grouped together, the long- and short-acting analogs accounted for 92.7% of visits in 2016 and 86.3% in 2020, while the human insulins represented just 7.3% of visits in 2016 and 5.5% in 2020.

The biosimilar analog insulins (glargine and lispro) first appeared in the database in 2017, accounting for 2.6% of visits that year and 8.2% by 2020.

Overall, the number of visits for insulin treatment declined by 18% between 2016 and 2020, from 6.0 million to 4.9 million. That drop may be due to multiple factors, Dr. Kalyani said.

“Recently updated clinical practice guidelines from professional societies such as the American Diabetes Association recommend the use of glucagon-like peptide-1 (GLP-1) receptor agonists prior to insulin when injectable medications are being considered [for type 2 diabetes],” she noted.

“In addition, during the pandemic, patients may not have been seeing their health care providers for routine diabetes care as often as before ... These and other factors may have contributed to the decrease in insulin visits that we observed.”

By specific insulins, glargine has topped the list all along, accounting for about half of all treatment visits, at 52.6% in 2020. Degludec came in second, at 17.4%, and lispro third, at 9.5%.

Use of pen devices also increased

The proportion of treatment visits for insulin vials/syringes declined from 63.9% in 2016 to 41.1% in 2020, while visits for insulin pens rose from 36.1% to 58.7%.

“Many pens are more costly compared to vials of the same insulin product. Interestingly, some studies have found that use of insulin pens may promote greater patient adherence to insulin and, as a result, more broadly decrease health care costs associated with diabetes. However, we did not specifically investigate the cost of insulin in our study,” Dr. Kalyani noted.

The proportion of visits for “newer” insulins, defined as those approved in 2010 or later, rose from 18.1% in 2016 to 40.9% in 2020, while the concurrent drop for insulins approved prior to 2010 was from 81.9% to 59.1%.

“The findings of our study provide insight into potential drivers of insulin costs in the U.S. and may inform health policy,” the researchers conclude.

Funded in part by the National Heart, Lung, and Blood Institute. Dr. Kalyani currently serves on the Endocrinologic and Metabolic Drugs Advisory Committee of the U.S. Food and Drug Administration.

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

Despite the extensive recent focus on its cost, insulin use in the United States remains dominated by insulin glargine and other analogs, as well as pen devices for delivery, new research shows.

The findings come from a nationally representative audit of outpatient care with input from nearly 5,000 physicians who prescribed insulin to patients with type 2 diabetes in 2016-2020.

The dramatic rise in the price of insulin in the United States has been extensively discussed in recent years, particularly with the newer analogs as compared with older human insulins.

Few studies indicate analog insulins better than human insulins

“Our findings suggest that even with increased public scrutiny for insulin products ... [the market is] dominated by the use of insulin analogs and insulin pen delivery devices, with persistent uptake of newer products as they are approved,” lead author Rita R. Kalyani, MD, told this news organization.

“Though newer insulins offer potentially greater flexibility with reduced hypoglycemia for many patients, they are also much more costly, with minimal to no head-to-head studies suggesting significant differences in glucose-lowering efficacy when compared to human insulins,” she stressed.

“We found it surprising that, despite the much-publicized concerns regarding insulin costs, analog insulins continue to represent more than 80% of insulin visits in the U.S.” added Dr. Kalyani, of the Division of Endocrinology, Diabetes & Metabolism at Johns Hopkins University School of Medicine, Baltimore.

However, as expected, the study also revealed a gradual increased uptake in the use of biosimilar insulins as more have been introduced to the market.

Dr. Kalyani advised, “Clinicians should be aware of their individual prescribing patterns for insulin and consider the affordability of insulin for patients as part of shared decision-making during clinic visits, particularly given the greater financial strain that many patients have faced during the ongoing COVID-19 pandemic and the rising societal costs for diabetes care.”

The research was published online October 12 in JAMA Network Open by Dr. Kalyani and colleagues.

Analogs prevailed, while biosimilar use rose

The data come from the Health National Disease and Therapeutic Index, a quarterly sampling of approximately 4,800 physicians that provides nationally representative diagnostic and prescribing information on patients treated by office-based physicians in the United States.

Overall, there were 27,860,691 insulin treatment visits for type 2 diabetes in 2016-2020. Of those, long-acting analog insulins (glargine [Lantus], detemir [Levemir], and degludec [Tresiba]) accounted for 67.3% of treatment visits in 2016 and 74.8% of treatment visits in 2020.

Rapid-acting insulin analogs (lispro [Humalog], aspart [Novolog], faster aspart [Fiasp], and glulisine [Apidra]) accounted for about 21.2% of visits in 2016 and about 16.5% in 2020.

On the other hand, intermediate- and short-acting human insulins (NPH and regular) accounted for just 3.7% of visits in 2016 and 2.6% in 2020.

Grouped together, the long- and short-acting analogs accounted for 92.7% of visits in 2016 and 86.3% in 2020, while the human insulins represented just 7.3% of visits in 2016 and 5.5% in 2020.

The biosimilar analog insulins (glargine and lispro) first appeared in the database in 2017, accounting for 2.6% of visits that year and 8.2% by 2020.

Overall, the number of visits for insulin treatment declined by 18% between 2016 and 2020, from 6.0 million to 4.9 million. That drop may be due to multiple factors, Dr. Kalyani said.

“Recently updated clinical practice guidelines from professional societies such as the American Diabetes Association recommend the use of glucagon-like peptide-1 (GLP-1) receptor agonists prior to insulin when injectable medications are being considered [for type 2 diabetes],” she noted.

“In addition, during the pandemic, patients may not have been seeing their health care providers for routine diabetes care as often as before ... These and other factors may have contributed to the decrease in insulin visits that we observed.”

By specific insulins, glargine has topped the list all along, accounting for about half of all treatment visits, at 52.6% in 2020. Degludec came in second, at 17.4%, and lispro third, at 9.5%.

Use of pen devices also increased

The proportion of treatment visits for insulin vials/syringes declined from 63.9% in 2016 to 41.1% in 2020, while visits for insulin pens rose from 36.1% to 58.7%.

“Many pens are more costly compared to vials of the same insulin product. Interestingly, some studies have found that use of insulin pens may promote greater patient adherence to insulin and, as a result, more broadly decrease health care costs associated with diabetes. However, we did not specifically investigate the cost of insulin in our study,” Dr. Kalyani noted.

The proportion of visits for “newer” insulins, defined as those approved in 2010 or later, rose from 18.1% in 2016 to 40.9% in 2020, while the concurrent drop for insulins approved prior to 2010 was from 81.9% to 59.1%.

“The findings of our study provide insight into potential drivers of insulin costs in the U.S. and may inform health policy,” the researchers conclude.

Funded in part by the National Heart, Lung, and Blood Institute. Dr. Kalyani currently serves on the Endocrinologic and Metabolic Drugs Advisory Committee of the U.S. Food and Drug Administration.

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

A newly published consensus statement on the management of type 1 diabetes in adults addresses the unique clinical needs of the population compared with those of children with type 1 diabetes or adults with type 2 diabetes.

“The focus on adults is kind of new and it is important. ... I do think it’s a bit of a forgotten population. Whenever we talk about diabetes in adults it’s assumed to be about type 2,” document coauthor M. Sue Kirkman, MD, said in an interview.

The document covers diagnosis of type 1 diabetes, goals and targets, schedule of care, self-management education and lifestyle, glucose monitoring, insulin therapy, hypoglycemia, psychosocial care, diabetic ketoacidosis (DKA), pancreas transplant/islet cell transplantation, adjunctive therapies, special populations (pregnant, older, hospitalized), and emergent and future perspectives.

Initially presented in draft form in June at the American Diabetes Association (ADA) 81st scientific sessions, the final version of the joint ADA/EASD statement was presented Oct. 1 at the annual meeting of the European Association for the Study of Diabetes and simultaneously published in Diabetologia and Diabetes Care.

“We are aware of the many and rapid advances in the diagnosis and treatment of type 1 diabetes ... However, despite these advances, there is also a growing recognition of the psychosocial burden of living with type 1 diabetes,” writing group cochair Richard I.G. Holt, MB BChir, PhD, professor of diabetes and endocrinology at the University of Southampton, England, said when introducing the 90-minute EASD session.

“Although there is guidance for the management of type 1 diabetes, the aim of this report is to highlight the major areas that health care professionals should consider when managing adults with type 1 diabetes,” he added.

Noting that the joint EASD/ADA consensus report on type 2 diabetes has been “highly influential,” Dr. Holt said, “EASD and ADA recognized the need to develop a comparable consensus report specifically addressing type 1 diabetes.”

The overriding goals, Dr. Holt said, are to “support people with type 1 diabetes to live a long and healthy life” with four specific strategies: delivery of insulin to keep glucose levels as close to target as possible to prevent complications while minimizing hypoglycemia and preventing DKA; managing cardiovascular risk factors; minimizing psychosocial burden; and promoting psychological well-being.
 

Diagnostic algorithm

Another coauthor, J. Hans de Vries, MD, PhD, professor of internal medicine at the University of Amsterdam, explained the recommended approach to distinguishing type 1 diabetes from type 2 diabetes or monogenic diabetes in adults, which is often a clinical challenge.

This also was the topic prompting the most questions during the EASD session.

“Especially in adults, misdiagnosis of type of diabetes is common, occurring in up to 40% of patients diagnosed after the age of 30 years,” Dr. de Vries said.

Among the many reasons for the confusion are that C-peptide levels, a reflection of endogenous insulin secretion, can still be relatively high at the time of clinical onset of type 1 diabetes, but islet antibodies don’t have 100% positive predictive value.

Obesity and type 2 diabetes are increasingly seen at younger ages, and DKA can occur in type 2 diabetes (“ketosis-prone”). In addition, monogenic forms of diabetes can be disguised as type 1 diabetes.

“So, we thought there was a need for a diagnostic algorithm,” Dr. de Vries said, adding that the algorithm – displayed as a graphic in the statement – is only for adults in whom type 1 diabetes is suspected, not other types. Also, it’s based on data from White European populations.

The first step is to test islet autoantibodies. If positive, the diagnosis of type 1 diabetes can be made. If negative and the person is younger than 35 years and without signs of type 2 diabetes, testing C-peptide is advised. If that’s below 200 pmol/L, type 1 diabetes is the diagnosis. If above 200 pmol/L, genetic testing for monogenic diabetes is advised. If there are signs of type 2 diabetes and/or the person is over age 35, type 2 diabetes is the most likely diagnosis.

And if uncertainty remains, the recommendation is to try noninsulin therapy and retest C-peptide again in 3 years, as by that time it will be below 200 pmol/L in a person with type 1 diabetes.

Dr. Kirkman commented regarding the algorithm: “It’s very much from a European population perspective. In some ways that’s a limitation, especially in the U.S. where the population is diverse, but I do think it’s still useful to help guide people through how to think about somebody who presents as an adult where it’s not obviously type 2 or type 1 ... There is a lot of in-between stuff.”
 

Psychosocial support: Essential but often overlooked

Frank J. Snoek, PhD, professor of psychology at Amsterdam University Medical Centers, Vrije Universiteit, presented the section on behavioral and psychosocial care. He pointed out that diabetes-related emotional distress is reported by 20%-40% of adults with type 1 diabetes, and that the risk of such distress is especially high at the time of diagnosis and when complications develop.

About 15% of people with type 1 diabetes have depression, which is linked to elevated A1c levels, increased complication risk, and mortality. Anxiety also is very common and linked with diabetes-specific fears including hypoglycemia. Eating disorders are more prevalent among people with type 1 diabetes than in the general population and can further complicate diabetes management.

Recommendations include periodic evaluation of psychological health and social barriers to self-management and having clear referral pathways and access to psychological or psychiatric care for individuals in need. “All members of the diabetes care team have a responsibility when it comes to offering psychosocial support as part of ongoing diabetes care and education.”

Dr. Kirkman had identified this section as noteworthy: “I think the focus on psychosocial care and making that an ongoing part of diabetes care and assessment is important.”

More data needed on diets, many other areas

During the discussion, several attendees asked about low-carbohydrate diets, embraced by many individuals with type 1 diabetes.

The document states: “While low-carbohydrate and very low-carbohydrate eating patterns have become increasingly popular and reduce A1c levels in the short term, it is important to incorporate these in conjunction with healthy eating guidelines. Additional components of the meal, including high fat and/or high protein, may contribute to delayed hyperglycemia and the need for insulin dose adjustments. Since this is highly variable between individuals, postprandial glucose measurements for up to 3 hours or more may be needed to determine initial dose adjustments.”

Beyond that, Tomasz Klupa, MD, PhD, of the department of metabolic diseases, Jagiellonian University, Krakow, Poland, responded: “We don’t have much data on low-carb diets in type 1 diabetes. ... Compliance to those diets is pretty poor. We don’t have long-term follow-up and the studies are simply not conclusive. Initial results do show reductions in body weight and A1c, but with time the compliance goes down dramatically.”

“Certainly, when we think of low-carb diets, we have to meet our patients where they are,” said Amy Hess-Fischl, a nutritionist and certified diabetes care and education specialist at the University of Chicago. “We don’t have enough data to really say there’s positive long-term evidence. But we can find a happy medium to find some benefits in glycemic and weight control. ... It’s really that collaboration with that person to identify what’s going to work for them in a healthy way.”

The EASD session concluded with writing group cochair Anne L. Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles, summing up the many other knowledge gaps, including personalizing use of diabetes technology, the problems of health disparities and lack of access to care, and the feasibility of prevention and/or cure.  

She observed: “There is no one-size-fits-all approach to diabetes care, and the more we can individualize our approaches, the more successful we are likely to be. ... Hopefully this consensus statement has pushed the bar a bit higher, telling the powers that be that people with type 1 diabetes need and deserve the best.

“We have a very long way to go before all of our patients reach their goals and health equity is achieved. ... We need to provide each and every person the access to the care we describe in this consensus statement, so that all can prosper and thrive and look forward to a long and healthy life lived with type 1 diabetes.”  

Dr. Holt has financial relationships with Novo Nordisk, Abbott, Eli Lilly, Otsuka, and Roche. Dr. de Vries has financial relationships with Afon, Eli Lilly, Novo Nordisk, Adocia, and Zealand Pharma. Ms. Hess-Fischl has financial relationships with Abbott Diabetes Care and Xeris. Dr. Klupa has financial relationships with numerous drug and device companies. Dr. Snoek has financial relationships with Abbott, Eli Lilly, Sanofi, and Novo Nordisk. Dr. Peters has financial relationships with Abbott Diabetes Care, Dexcom, Eli Lilly, Insulet, Novo Nordisk, Medscape, and Zealand Pharmaceuticals. She holds stock options in Omada Health and Livongo and is a special government employee of the Food and Drug Administration.
 

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

A newly published consensus statement on the management of type 1 diabetes in adults addresses the unique clinical needs of the population compared with those of children with type 1 diabetes or adults with type 2 diabetes.

“The focus on adults is kind of new and it is important. ... I do think it’s a bit of a forgotten population. Whenever we talk about diabetes in adults it’s assumed to be about type 2,” document coauthor M. Sue Kirkman, MD, said in an interview.

The document covers diagnosis of type 1 diabetes, goals and targets, schedule of care, self-management education and lifestyle, glucose monitoring, insulin therapy, hypoglycemia, psychosocial care, diabetic ketoacidosis (DKA), pancreas transplant/islet cell transplantation, adjunctive therapies, special populations (pregnant, older, hospitalized), and emergent and future perspectives.

Initially presented in draft form in June at the American Diabetes Association (ADA) 81st scientific sessions, the final version of the joint ADA/EASD statement was presented Oct. 1 at the annual meeting of the European Association for the Study of Diabetes and simultaneously published in Diabetologia and Diabetes Care.

“We are aware of the many and rapid advances in the diagnosis and treatment of type 1 diabetes ... However, despite these advances, there is also a growing recognition of the psychosocial burden of living with type 1 diabetes,” writing group cochair Richard I.G. Holt, MB BChir, PhD, professor of diabetes and endocrinology at the University of Southampton, England, said when introducing the 90-minute EASD session.

“Although there is guidance for the management of type 1 diabetes, the aim of this report is to highlight the major areas that health care professionals should consider when managing adults with type 1 diabetes,” he added.

Noting that the joint EASD/ADA consensus report on type 2 diabetes has been “highly influential,” Dr. Holt said, “EASD and ADA recognized the need to develop a comparable consensus report specifically addressing type 1 diabetes.”

The overriding goals, Dr. Holt said, are to “support people with type 1 diabetes to live a long and healthy life” with four specific strategies: delivery of insulin to keep glucose levels as close to target as possible to prevent complications while minimizing hypoglycemia and preventing DKA; managing cardiovascular risk factors; minimizing psychosocial burden; and promoting psychological well-being.
 

Diagnostic algorithm

Another coauthor, J. Hans de Vries, MD, PhD, professor of internal medicine at the University of Amsterdam, explained the recommended approach to distinguishing type 1 diabetes from type 2 diabetes or monogenic diabetes in adults, which is often a clinical challenge.

This also was the topic prompting the most questions during the EASD session.

“Especially in adults, misdiagnosis of type of diabetes is common, occurring in up to 40% of patients diagnosed after the age of 30 years,” Dr. de Vries said.

Among the many reasons for the confusion are that C-peptide levels, a reflection of endogenous insulin secretion, can still be relatively high at the time of clinical onset of type 1 diabetes, but islet antibodies don’t have 100% positive predictive value.

Obesity and type 2 diabetes are increasingly seen at younger ages, and DKA can occur in type 2 diabetes (“ketosis-prone”). In addition, monogenic forms of diabetes can be disguised as type 1 diabetes.

“So, we thought there was a need for a diagnostic algorithm,” Dr. de Vries said, adding that the algorithm – displayed as a graphic in the statement – is only for adults in whom type 1 diabetes is suspected, not other types. Also, it’s based on data from White European populations.

The first step is to test islet autoantibodies. If positive, the diagnosis of type 1 diabetes can be made. If negative and the person is younger than 35 years and without signs of type 2 diabetes, testing C-peptide is advised. If that’s below 200 pmol/L, type 1 diabetes is the diagnosis. If above 200 pmol/L, genetic testing for monogenic diabetes is advised. If there are signs of type 2 diabetes and/or the person is over age 35, type 2 diabetes is the most likely diagnosis.

And if uncertainty remains, the recommendation is to try noninsulin therapy and retest C-peptide again in 3 years, as by that time it will be below 200 pmol/L in a person with type 1 diabetes.

Dr. Kirkman commented regarding the algorithm: “It’s very much from a European population perspective. In some ways that’s a limitation, especially in the U.S. where the population is diverse, but I do think it’s still useful to help guide people through how to think about somebody who presents as an adult where it’s not obviously type 2 or type 1 ... There is a lot of in-between stuff.”
 

Psychosocial support: Essential but often overlooked

Frank J. Snoek, PhD, professor of psychology at Amsterdam University Medical Centers, Vrije Universiteit, presented the section on behavioral and psychosocial care. He pointed out that diabetes-related emotional distress is reported by 20%-40% of adults with type 1 diabetes, and that the risk of such distress is especially high at the time of diagnosis and when complications develop.

About 15% of people with type 1 diabetes have depression, which is linked to elevated A1c levels, increased complication risk, and mortality. Anxiety also is very common and linked with diabetes-specific fears including hypoglycemia. Eating disorders are more prevalent among people with type 1 diabetes than in the general population and can further complicate diabetes management.

Recommendations include periodic evaluation of psychological health and social barriers to self-management and having clear referral pathways and access to psychological or psychiatric care for individuals in need. “All members of the diabetes care team have a responsibility when it comes to offering psychosocial support as part of ongoing diabetes care and education.”

Dr. Kirkman had identified this section as noteworthy: “I think the focus on psychosocial care and making that an ongoing part of diabetes care and assessment is important.”

More data needed on diets, many other areas

During the discussion, several attendees asked about low-carbohydrate diets, embraced by many individuals with type 1 diabetes.

The document states: “While low-carbohydrate and very low-carbohydrate eating patterns have become increasingly popular and reduce A1c levels in the short term, it is important to incorporate these in conjunction with healthy eating guidelines. Additional components of the meal, including high fat and/or high protein, may contribute to delayed hyperglycemia and the need for insulin dose adjustments. Since this is highly variable between individuals, postprandial glucose measurements for up to 3 hours or more may be needed to determine initial dose adjustments.”

Beyond that, Tomasz Klupa, MD, PhD, of the department of metabolic diseases, Jagiellonian University, Krakow, Poland, responded: “We don’t have much data on low-carb diets in type 1 diabetes. ... Compliance to those diets is pretty poor. We don’t have long-term follow-up and the studies are simply not conclusive. Initial results do show reductions in body weight and A1c, but with time the compliance goes down dramatically.”

“Certainly, when we think of low-carb diets, we have to meet our patients where they are,” said Amy Hess-Fischl, a nutritionist and certified diabetes care and education specialist at the University of Chicago. “We don’t have enough data to really say there’s positive long-term evidence. But we can find a happy medium to find some benefits in glycemic and weight control. ... It’s really that collaboration with that person to identify what’s going to work for them in a healthy way.”

The EASD session concluded with writing group cochair Anne L. Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles, summing up the many other knowledge gaps, including personalizing use of diabetes technology, the problems of health disparities and lack of access to care, and the feasibility of prevention and/or cure.  

She observed: “There is no one-size-fits-all approach to diabetes care, and the more we can individualize our approaches, the more successful we are likely to be. ... Hopefully this consensus statement has pushed the bar a bit higher, telling the powers that be that people with type 1 diabetes need and deserve the best.

“We have a very long way to go before all of our patients reach their goals and health equity is achieved. ... We need to provide each and every person the access to the care we describe in this consensus statement, so that all can prosper and thrive and look forward to a long and healthy life lived with type 1 diabetes.”  

Dr. Holt has financial relationships with Novo Nordisk, Abbott, Eli Lilly, Otsuka, and Roche. Dr. de Vries has financial relationships with Afon, Eli Lilly, Novo Nordisk, Adocia, and Zealand Pharma. Ms. Hess-Fischl has financial relationships with Abbott Diabetes Care and Xeris. Dr. Klupa has financial relationships with numerous drug and device companies. Dr. Snoek has financial relationships with Abbott, Eli Lilly, Sanofi, and Novo Nordisk. Dr. Peters has financial relationships with Abbott Diabetes Care, Dexcom, Eli Lilly, Insulet, Novo Nordisk, Medscape, and Zealand Pharmaceuticals. She holds stock options in Omada Health and Livongo and is a special government employee of the Food and Drug Administration.
 

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

A newly published consensus statement on the management of type 1 diabetes in adults addresses the unique clinical needs of the population compared with those of children with type 1 diabetes or adults with type 2 diabetes.

“The focus on adults is kind of new and it is important. ... I do think it’s a bit of a forgotten population. Whenever we talk about diabetes in adults it’s assumed to be about type 2,” document coauthor M. Sue Kirkman, MD, said in an interview.

The document covers diagnosis of type 1 diabetes, goals and targets, schedule of care, self-management education and lifestyle, glucose monitoring, insulin therapy, hypoglycemia, psychosocial care, diabetic ketoacidosis (DKA), pancreas transplant/islet cell transplantation, adjunctive therapies, special populations (pregnant, older, hospitalized), and emergent and future perspectives.

Initially presented in draft form in June at the American Diabetes Association (ADA) 81st scientific sessions, the final version of the joint ADA/EASD statement was presented Oct. 1 at the annual meeting of the European Association for the Study of Diabetes and simultaneously published in Diabetologia and Diabetes Care.

“We are aware of the many and rapid advances in the diagnosis and treatment of type 1 diabetes ... However, despite these advances, there is also a growing recognition of the psychosocial burden of living with type 1 diabetes,” writing group cochair Richard I.G. Holt, MB BChir, PhD, professor of diabetes and endocrinology at the University of Southampton, England, said when introducing the 90-minute EASD session.

“Although there is guidance for the management of type 1 diabetes, the aim of this report is to highlight the major areas that health care professionals should consider when managing adults with type 1 diabetes,” he added.

Noting that the joint EASD/ADA consensus report on type 2 diabetes has been “highly influential,” Dr. Holt said, “EASD and ADA recognized the need to develop a comparable consensus report specifically addressing type 1 diabetes.”

The overriding goals, Dr. Holt said, are to “support people with type 1 diabetes to live a long and healthy life” with four specific strategies: delivery of insulin to keep glucose levels as close to target as possible to prevent complications while minimizing hypoglycemia and preventing DKA; managing cardiovascular risk factors; minimizing psychosocial burden; and promoting psychological well-being.
 

Diagnostic algorithm

Another coauthor, J. Hans de Vries, MD, PhD, professor of internal medicine at the University of Amsterdam, explained the recommended approach to distinguishing type 1 diabetes from type 2 diabetes or monogenic diabetes in adults, which is often a clinical challenge.

This also was the topic prompting the most questions during the EASD session.

“Especially in adults, misdiagnosis of type of diabetes is common, occurring in up to 40% of patients diagnosed after the age of 30 years,” Dr. de Vries said.

Among the many reasons for the confusion are that C-peptide levels, a reflection of endogenous insulin secretion, can still be relatively high at the time of clinical onset of type 1 diabetes, but islet antibodies don’t have 100% positive predictive value.

Obesity and type 2 diabetes are increasingly seen at younger ages, and DKA can occur in type 2 diabetes (“ketosis-prone”). In addition, monogenic forms of diabetes can be disguised as type 1 diabetes.

“So, we thought there was a need for a diagnostic algorithm,” Dr. de Vries said, adding that the algorithm – displayed as a graphic in the statement – is only for adults in whom type 1 diabetes is suspected, not other types. Also, it’s based on data from White European populations.

The first step is to test islet autoantibodies. If positive, the diagnosis of type 1 diabetes can be made. If negative and the person is younger than 35 years and without signs of type 2 diabetes, testing C-peptide is advised. If that’s below 200 pmol/L, type 1 diabetes is the diagnosis. If above 200 pmol/L, genetic testing for monogenic diabetes is advised. If there are signs of type 2 diabetes and/or the person is over age 35, type 2 diabetes is the most likely diagnosis.

And if uncertainty remains, the recommendation is to try noninsulin therapy and retest C-peptide again in 3 years, as by that time it will be below 200 pmol/L in a person with type 1 diabetes.

Dr. Kirkman commented regarding the algorithm: “It’s very much from a European population perspective. In some ways that’s a limitation, especially in the U.S. where the population is diverse, but I do think it’s still useful to help guide people through how to think about somebody who presents as an adult where it’s not obviously type 2 or type 1 ... There is a lot of in-between stuff.”
 

Psychosocial support: Essential but often overlooked

Frank J. Snoek, PhD, professor of psychology at Amsterdam University Medical Centers, Vrije Universiteit, presented the section on behavioral and psychosocial care. He pointed out that diabetes-related emotional distress is reported by 20%-40% of adults with type 1 diabetes, and that the risk of such distress is especially high at the time of diagnosis and when complications develop.

About 15% of people with type 1 diabetes have depression, which is linked to elevated A1c levels, increased complication risk, and mortality. Anxiety also is very common and linked with diabetes-specific fears including hypoglycemia. Eating disorders are more prevalent among people with type 1 diabetes than in the general population and can further complicate diabetes management.

Recommendations include periodic evaluation of psychological health and social barriers to self-management and having clear referral pathways and access to psychological or psychiatric care for individuals in need. “All members of the diabetes care team have a responsibility when it comes to offering psychosocial support as part of ongoing diabetes care and education.”

Dr. Kirkman had identified this section as noteworthy: “I think the focus on psychosocial care and making that an ongoing part of diabetes care and assessment is important.”

More data needed on diets, many other areas

During the discussion, several attendees asked about low-carbohydrate diets, embraced by many individuals with type 1 diabetes.

The document states: “While low-carbohydrate and very low-carbohydrate eating patterns have become increasingly popular and reduce A1c levels in the short term, it is important to incorporate these in conjunction with healthy eating guidelines. Additional components of the meal, including high fat and/or high protein, may contribute to delayed hyperglycemia and the need for insulin dose adjustments. Since this is highly variable between individuals, postprandial glucose measurements for up to 3 hours or more may be needed to determine initial dose adjustments.”

Beyond that, Tomasz Klupa, MD, PhD, of the department of metabolic diseases, Jagiellonian University, Krakow, Poland, responded: “We don’t have much data on low-carb diets in type 1 diabetes. ... Compliance to those diets is pretty poor. We don’t have long-term follow-up and the studies are simply not conclusive. Initial results do show reductions in body weight and A1c, but with time the compliance goes down dramatically.”

“Certainly, when we think of low-carb diets, we have to meet our patients where they are,” said Amy Hess-Fischl, a nutritionist and certified diabetes care and education specialist at the University of Chicago. “We don’t have enough data to really say there’s positive long-term evidence. But we can find a happy medium to find some benefits in glycemic and weight control. ... It’s really that collaboration with that person to identify what’s going to work for them in a healthy way.”

The EASD session concluded with writing group cochair Anne L. Peters, MD, director of clinical diabetes programs at the University of Southern California, Los Angeles, summing up the many other knowledge gaps, including personalizing use of diabetes technology, the problems of health disparities and lack of access to care, and the feasibility of prevention and/or cure.  

She observed: “There is no one-size-fits-all approach to diabetes care, and the more we can individualize our approaches, the more successful we are likely to be. ... Hopefully this consensus statement has pushed the bar a bit higher, telling the powers that be that people with type 1 diabetes need and deserve the best.

“We have a very long way to go before all of our patients reach their goals and health equity is achieved. ... We need to provide each and every person the access to the care we describe in this consensus statement, so that all can prosper and thrive and look forward to a long and healthy life lived with type 1 diabetes.”  

Dr. Holt has financial relationships with Novo Nordisk, Abbott, Eli Lilly, Otsuka, and Roche. Dr. de Vries has financial relationships with Afon, Eli Lilly, Novo Nordisk, Adocia, and Zealand Pharma. Ms. Hess-Fischl has financial relationships with Abbott Diabetes Care and Xeris. Dr. Klupa has financial relationships with numerous drug and device companies. Dr. Snoek has financial relationships with Abbott, Eli Lilly, Sanofi, and Novo Nordisk. Dr. Peters has financial relationships with Abbott Diabetes Care, Dexcom, Eli Lilly, Insulet, Novo Nordisk, Medscape, and Zealand Pharmaceuticals. She holds stock options in Omada Health and Livongo and is a special government employee of the Food and Drug Administration.
 

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

Medtronic has updated a previous recall of its MiniMed 600 series insulin pumps to include all with a potentially problematic clear retainer ring, not just those that appear damaged.

The U.S. Food and Drug Administration announced on Oct. 5 that Medtronic will now replace any MiniMed 600 series pump that has a clear retainer ring with an updated pump that includes a black retainer ring at no extra charge, regardless of warranty status.

In November 2019, Medtronic first advised patients to examine their pumps for potential damage to the ring, and to contact the company if it appeared to be loose, damaged, or missing. In February 2020, the FDA designated the recall as class 1, “the most serious type of recall,” for which use of the devices “may cause serious injuries or death.”

In this case, one potential risk is hyperglycemia. This can occur if the reservoir isn’t properly locked into place by the retainer ring, and insulin isn’t infused into the body. That, in turn, can lead to diabetic ketoacidosis. Another risk is hypoglycemia, which could result from over-delivery of insulin if the retainer ring breaks or detaches and the user inserts the reservoir back into the pump with the infusion set still connected to the body.

While serious injuries and deaths have been reported with the use of Minimed series 600 insulin pumps, “those adverse events may not have been directly related to the damaged clear retainer rings that are the basis for this recall,” according to the FDA notice. Nonetheless, lawsuits have reportedly been filed.

The new update is not a result of any new issues, Medtronic spokesperson Pamela Reese told this news organization. “Medtronic will proactively replace all MiniMed 600 series insulin pumps with the clear retainer ring design with an equivalent pump that has an updated black retainer ring design, which is designed to better withstand damage sustained by an accidental drop or bump on a hard surface.”

She added, “As we analyze the information that we continuously collect on the safety and performance of our insulin pumps, we recognize that patients who are still using the clear retainer ring could potentially encounter future problems. Therefore, we are currently accelerating our replacement as inventory allows over the coming months to eliminate any potential performance concerns and optimize patient safety and experience.”

The company has replaced nearly half of the clear retainer ring pumps that were in use since November 2019, she said.

The specific insulin pump products are the model 630G, distributed between September 2016 and February 2020; and the 670G, distributed between May 2015 and December 2020. The 630G is approved for people aged 16 years and older, and the 670G – which works with a continuous glucose monitor in a “hybrid closed-loop system – is available for people with type 1 diabetes as young as 7 years of age.

Medtronic has updated a previous recall of its MiniMed 600 series insulin pumps to include all with a potentially problematic clear retainer ring, not just those that appear damaged.

The U.S. Food and Drug Administration announced on Oct. 5 that Medtronic will now replace any MiniMed 600 series pump that has a clear retainer ring with an updated pump that includes a black retainer ring at no extra charge, regardless of warranty status.

In November 2019, Medtronic first advised patients to examine their pumps for potential damage to the ring, and to contact the company if it appeared to be loose, damaged, or missing. In February 2020, the FDA designated the recall as class 1, “the most serious type of recall,” for which use of the devices “may cause serious injuries or death.”

In this case, one potential risk is hyperglycemia. This can occur if the reservoir isn’t properly locked into place by the retainer ring, and insulin isn’t infused into the body. That, in turn, can lead to diabetic ketoacidosis. Another risk is hypoglycemia, which could result from over-delivery of insulin if the retainer ring breaks or detaches and the user inserts the reservoir back into the pump with the infusion set still connected to the body.

While serious injuries and deaths have been reported with the use of Minimed series 600 insulin pumps, “those adverse events may not have been directly related to the damaged clear retainer rings that are the basis for this recall,” according to the FDA notice. Nonetheless, lawsuits have reportedly been filed.

The new update is not a result of any new issues, Medtronic spokesperson Pamela Reese told this news organization. “Medtronic will proactively replace all MiniMed 600 series insulin pumps with the clear retainer ring design with an equivalent pump that has an updated black retainer ring design, which is designed to better withstand damage sustained by an accidental drop or bump on a hard surface.”

She added, “As we analyze the information that we continuously collect on the safety and performance of our insulin pumps, we recognize that patients who are still using the clear retainer ring could potentially encounter future problems. Therefore, we are currently accelerating our replacement as inventory allows over the coming months to eliminate any potential performance concerns and optimize patient safety and experience.”

The company has replaced nearly half of the clear retainer ring pumps that were in use since November 2019, she said.

The specific insulin pump products are the model 630G, distributed between September 2016 and February 2020; and the 670G, distributed between May 2015 and December 2020. The 630G is approved for people aged 16 years and older, and the 670G – which works with a continuous glucose monitor in a “hybrid closed-loop system – is available for people with type 1 diabetes as young as 7 years of age.

Medtronic has updated a previous recall of its MiniMed 600 series insulin pumps to include all with a potentially problematic clear retainer ring, not just those that appear damaged.

The U.S. Food and Drug Administration announced on Oct. 5 that Medtronic will now replace any MiniMed 600 series pump that has a clear retainer ring with an updated pump that includes a black retainer ring at no extra charge, regardless of warranty status.

In November 2019, Medtronic first advised patients to examine their pumps for potential damage to the ring, and to contact the company if it appeared to be loose, damaged, or missing. In February 2020, the FDA designated the recall as class 1, “the most serious type of recall,” for which use of the devices “may cause serious injuries or death.”

In this case, one potential risk is hyperglycemia. This can occur if the reservoir isn’t properly locked into place by the retainer ring, and insulin isn’t infused into the body. That, in turn, can lead to diabetic ketoacidosis. Another risk is hypoglycemia, which could result from over-delivery of insulin if the retainer ring breaks or detaches and the user inserts the reservoir back into the pump with the infusion set still connected to the body.

While serious injuries and deaths have been reported with the use of Minimed series 600 insulin pumps, “those adverse events may not have been directly related to the damaged clear retainer rings that are the basis for this recall,” according to the FDA notice. Nonetheless, lawsuits have reportedly been filed.

The new update is not a result of any new issues, Medtronic spokesperson Pamela Reese told this news organization. “Medtronic will proactively replace all MiniMed 600 series insulin pumps with the clear retainer ring design with an equivalent pump that has an updated black retainer ring design, which is designed to better withstand damage sustained by an accidental drop or bump on a hard surface.”

She added, “As we analyze the information that we continuously collect on the safety and performance of our insulin pumps, we recognize that patients who are still using the clear retainer ring could potentially encounter future problems. Therefore, we are currently accelerating our replacement as inventory allows over the coming months to eliminate any potential performance concerns and optimize patient safety and experience.”

The company has replaced nearly half of the clear retainer ring pumps that were in use since November 2019, she said.

The specific insulin pump products are the model 630G, distributed between September 2016 and February 2020; and the 670G, distributed between May 2015 and December 2020. The 630G is approved for people aged 16 years and older, and the 670G – which works with a continuous glucose monitor in a “hybrid closed-loop system – is available for people with type 1 diabetes as young as 7 years of age.

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

A uniquely-designed three-drug study has demonstrated that individual clinical characteristics, including patient preference, can be used to guide medication choice in type 2 diabetes.

Results from the TriMaster trial using sitagliptin, pioglitazone, and canagliflozin as second- or third-line therapy in a total of 525 patients with type 2 diabetes were presented September 29 at the virtual European Association for the Study of Diabetes (EASD) 2021 Annual Meeting.

TriMaster is a phase 4, multicenter, randomized, double-blind, 12-month crossover trial examining the effects of all three drugs in subgroups of patients with type 2 diabetes who hadn’t achieved target glucose levels with metformin alone or combined with a sulfonylurea.   

While all three drugs lowered glucose similarly overall, pioglitazone did so more effectively among patients with a body mass index (BMI) above 30 kg/m², while sitagliptin worked better in those with a BMI less than 30 kg/m². However, pioglitazone resulted in more weight gain.

In a second comparison, canagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) was more effective than sitagliptin (a dipeptidyl peptidase-4 [DPP-4] inhibitor) in lowering glucose among patients with an estimated glomerular filtration rate (eGFR) above 90 mL/min/1.73m2, while sitagliptin actually lowered glucose better among individuals with an eGFR 60-90 mL/min/1.73m2 than canagliflozin.

And when participants were asked which drug they preferred, the results were split nearly evenly among the three, correlating with how well the drug worked and the side effect profile for each individual.  

“We proved a precision approach worked using predefined clinical criteria to define groups of patients where one drug is better than another. This is the first-ever proof of a precision medicine approach in type 2 diabetes,” chief investigator Andrew Hattersley, DM, professor of molecular medicine at the University of Exeter, U.K., told this news organization.

But, he stressed, “These results do not mean all patients with BMI above 30 should have pioglitazone or that all patients with an eGFR 60-90 should have a DPP-4 inhibitor.”

“Drug choice will need to consider other priorities than glycemia ... Patients with heart failure, cardiovascular disease, and chronic kidney disease should be prescribed SGLT2 inhibitors,” he noted. And “some patients will need to avoid specific drugs due to likely side effects.”
 

‘Modern era’ study used older drugs

Independent commentator Caroline M. Kistorp, MD, PhD, professor of endocrinology at University Hospital Copenhagen, congratulated the investigators for “moving precision medicine from the retrospective analysis of existing data into the modern era of evidence-based medicine with this randomized clinical trial in patients with type 2 diabetes ... Starting this trial back in 2015 was really ahead of their time.”

However, she questioned the use of a thiazolidinedione (TZD), pioglitazone, in the trial, as they are no longer used in many parts of the world in favor of more “modern” glucose-lowering drugs.

“I’m thinking of GLP-1 receptor agonists, especially if you want to treat type 2 diabetes patients who are obese with a BMI over 30 ... I acknowledge that there is a cost issue, but I still think we should try to give our patients the best treatments, so that’s why I’m not sure how much the [TZDs] will be used in the future, even with this trial,” she said.

Dr. Kistorp also noted the trial didn’t include cardiovascular disease outcomes, for which most SGLT2 inhibitors have shown benefit.

“We have to discuss and consider whether A1c is the most important parameter for these patients ... especially looking at their cardiovascular outcomes.” 

Mr. Hattersley responded that the study was designed in 2015, prior to the landmark EMPA-REG OUTCOME trial that began the shift toward use of SGLT2 inhibitors for cardiovascular and kidney disease reduction in addition to glycemic control in the clinical management of type 2 diabetes.

“We will report the cardiovascular profiles, but it wasn’t a specific thing because at that time the evidence didn’t exist, so it wasn’t in our protocol,” he explained.  

Regarding pioglitazone, he acknowledged that although it may be an alternative to insulin for some patients, “I think for most people you won’t be considering it in clinical practice,” but because it has a very different mechanism from the other two study drugs, “it did give the greater chance of differential effects ... Partly, what we’re really trying to do is test the question of whether precision medicine exists and can we do it.”
 

Unique study design had each patient act as their own control

Trial statistician Beverley Shields, PhD, of the University of Exeter, U.K., reported the results. The 525 participants with type 2 diabetes were aged 30-79 years and had A1c levels above 58 mmol/mol (7.5%) but not greater than 110 mmol/mol (12.2%) with metformin alone or combined with a sulfonylurea. Just over half (58%) had a BMI above 30 kg/m² and 52% had an eGFR greater than 90 mL/min/1.73m2.

Each participant received each of the three medications as second- or third-line oral therapy in random order – in one of six possible sequences – for 16 weeks each, with no washout period in between (to prevent dropouts due to hyperglycemia). Thus, each participant acted as their own control.

A total of 458 participants completed all three study periods.
 

The drugs work differently in different patient groups

Without stratification by patient type, there was no overall difference in A1c reduction between the three therapies, with all achieving about 59-60 mmol/mol (7.5-7.6%) from a baseline average of 69 mmol/mol (8.9%).

But when stratified by BMI, A1c was 1.48 mmol/mol higher with pioglitazone versus sitagliptin in the group with BMI less than 30 kg/m2 and 1.44 mmol/mol lower with pioglitazone versus sitagliptin in the group with BMI greater than 30 kg/m², giving a significant overall difference of 2.92 mmol/mol (P = .003).  

By eGFR stratification, A1c was 1.74 mmol/mol lower with sitagliptin than canagliflozin in the 60-90 mL/min/1.73m2 group and 1.08 mmol/mol higher in the greater than 90 mL/min/1.73m2 group, giving a significant difference of 2.83 mmol/mol (P = .002).

“So, if we were to treat the patients with the drug that is optimal for their strata ... this would lead to a benefit of about 3 mmol/mol compared to if those patients were treated with the other drug,” Dr. Shields said.

By BMI, there were no significant differences by drug or strata for tolerability, defined as staying on drug for at least 12 weeks (P = .2), nor in the percentage of patients reporting at least one hypoglycemic episode (P = .6).

However, pioglitazone was associated with higher weight gain in both BMI groups, resulting in a 0.93 kg difference overall (P < .001), although it was higher in the higher BMI group (1.9 vs. 0.97 kg).

Similarly, by eGFR there were no differences in tolerability or hypoglycemic episodes between sitagliptin and canagliflozin (P = .09 and P = .6, respectively). And here, there were no differences in weight (P = .6).
 

Patients compared their own experiences with each drug

Patients were asked about their drug preferences after being reminded about their own changes in A1c and weight with each one. The result was a split: 25.8% picked pioglitazone, 34.8% sitagliptin, and 38.7% canagliflozin.

Looking at study outcomes by therapy, pioglitazone had the lowest rate of nontolerability but the highest weight gain, sitagliptin had the highest nontolerability but the lowest number of side effects, while canagliflozin had the highest number of reported side effects but the lowest weight gain.  

Patients’ preferred drugs were associated with the lowest A1c and the fewest side effects for each group. Interestingly, pioglitazone was associated with the highest weight on therapy regardless of preference, so that even those who preferred pioglitazone had a higher weight than they did with the other two drugs.

In response to an audience question about durability of the results given the relatively short trial periods, Mr. Hattersley said: “We’re following up these patients who have chosen their drug, and on the whole, their primary care doctor agreed with them. So we’re following that up as a prospective cohort. We’re looking at tolerance and response and also to see if they’re still happy with that drug. That will be a future analysis.”

The TriMASTER data will be submitted for publication soon.

TriMASTER was funded by the UK Medical Research Council. Mr. Hattersley and Dr. Shields have reported no relevant financial relationships. Dr. Kistorp has reported receiving honoraria from and/or is on advisory boards for AstraZeneca, Novo Nordisk, Boehringer Ingelheim, MSD, Otsuka Pharma, and Chiesi.

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

Both high C-reactive protein (CRP) and older age predict mortality from COVID-19 in patients with diabetes, new research suggests.

The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.

The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.

“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.

“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”

“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.

“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
 

Kidney disease in younger patients also linked to poorer outcomes

The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.

They had a median BMI of 27.6 kg/m², which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.

The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.

A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.

On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).

In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).

As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.

In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.

Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.

“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”

Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.

“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.

Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.

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

Both high C-reactive protein (CRP) and older age predict mortality from COVID-19 in patients with diabetes, new research suggests.

The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.

The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.

“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.

“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”

“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.

“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
 

Kidney disease in younger patients also linked to poorer outcomes

The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.

They had a median BMI of 27.6 kg/m², which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.

The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.

A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.

On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).

In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).

As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.

In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.

Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.

“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”

Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.

“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.

Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.

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

Both high C-reactive protein (CRP) and older age predict mortality from COVID-19 in patients with diabetes, new research suggests.

The data, from the retrospective ACCREDIT cohort study, were presented at the virtual annual meeting of the European Association for the Study of Diabetes (EASD 2021) by Daniel Kevin Llanera, MD.

The combination of older age and high levels of the inflammatory marker CRP were linked to a tripled risk for death by day 7 after hospitalization for COVID-19 among people with diabetes. But, in contrast to other studies, recent A1c and body mass index did not predict COVID-19 outcomes.

“Both of these variables are easily available upon admission to hospital,” Dr. Llanera, who now works at Imperial College, London, said in an EASD press release.

“This means we can easily identify patients early on in their hospital stay who will likely require more aggressive interventions to try and improve survival.”

“It makes sense that CRP and age are important,” said Simon Heller, MB BChir, DM, of the University of Sheffield, England. “It may be that diabetes alone overwhelmed the additional effects of obesity and A1c.

“Certainly in other studies, age was the overwhelming bad prognostic sign among people with diabetes, and perhaps long-term diabetes has effects on the immune system which we haven’t yet identified.”
 

Kidney disease in younger patients also linked to poorer outcomes

The study, conducted when Dr. Llanera worked for the Countess of Chester NHS Foundation Trust, involved 1,004 patients with diabetes admitted with COVID-19 to seven hospitals in northwest England from Jan. 1 through June 30, 2020. The patients were a mean age of 74.1 years, 60.7% were male, and 45% were in the most deprived quintile based on the U.K. government deprivation index. Overall, 56.2% had macrovascular complications and 49.6% had microvascular complications.

They had a median BMI of 27.6 kg/m², which is lower than that reported in previous studies and might explain the difference, Dr. Llanera noted.

The primary outcome, death within 7 days of admission, occurred in 24%. By day 30, 33% had died. These rates are higher than the rate found in previous studies, possibly because of greater socioeconomic deprivation and older age of the population, Dr. Llanera speculated.

A total of 7.5% of patients received intensive care by day 7 and 9.8% required intravenous insulin infusions.

On univariate analysis, insulin infusion was found to be protective, with those receiving it half as likely to die as those who didn’t need IV insulin (odds ratio [OR], 0.5).

In contrast, chronic kidney disease in people younger than 70 years increased the risk of death more than twofold (OR, 2.74), as did type 2 diabetes compared with other diabetes types (OR, 2.52).

As in previous studies, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers were not associated with COVID-19 outcomes, nor was the presence of diabetes-related complications.

In multivariate analysis, CRP and age emerged as the most significant predictors of the primary outcome, with those deemed high risk by a logistic regression model having an OR of 3.44 for death by day 7 compared with those at lower risk based on the two factors.

Data for glycemic control during the time of hospitalization weren’t available for this study, Dr. Llanera said in response to a question.

“We didn’t look into glycemic control during admission, just at entry, so I can’t answer whether strict glucose control is of benefit. I think it’s worth exploring further whether the use of IV insulin may be of benefit.”

Dr. Llanera also pointed out that people with diabetic kidney disease are in a chronic proinflammatory state and have immune dysregulation, thus potentially hindering their ability to “fight off” the virus.

“In addition, ACE2 receptors are upregulated in the kidneys of patients with diabetic kidney disease. These are molecules that facilitate entry of SARS-CoV-2 into the cells. This may lead to direct attack of the kidneys by the virus, possibly leading to worse overall outcomes,” he said.

Dr. Llanera has reported no relevant financial relationships. Dr. Heller has reported serving as consultant or speaker for Novo Nordisk, Eli Lilly, Sanofi Aventis, Mannkind, Zealand, MSD, and Boehringer Ingelheim.

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

The annual meeting of the European Association for the Study of Diabetes 2021 will delve into individualized approaches in diabetes management, particularly with regard to tailoring drug therapy for type 2 diabetes and management of type 1 diabetes.  

Sara Freeman/MDedge News

The virtual meeting, taking place Sept. 28 to Oct. 1 in Central European Summer Time, will feature results from TriMASTER (a three-way cross-over trial of precision medicine strategy of second-/third-line therapy in type 2 diabetes), new subgroup analyses from the GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness) study, the final version of a consensus statement on type 1 diabetes management, and new data on the dual incretin agonist tirzepatide, as well as much more.

“I’m a strong believer in personalization. I don’t think the big blockbuster [drugs] will serve the entire community with diabetes. Even in type 1 diabetes, there’s evidence of heterogeneity. ... We need a better way to identify individual needs. I think that’s where we’re going. ... It’s one of the themes of the conference,” EASD President Stefano Del Prato, MD, professor of endocrinology at the University of Pisa (Italy), told this news organization.

He noted that EASD and the American Diabetes Association have recently teamed up with other organizations to form the Precision Medicine in Diabetes Initiative

As would be expected, the meeting will also feature numerous presentations on the COVID-19 pandemic, including studies looking at how people with COVID-19 and diabetes have fared; how the pandemic has affected diabetes care; and the still unclear impact of SARS-CoV-2 on pancreatic beta cells and whether, in some instances, it triggers new-onset diabetes.  
 

New data from previously reported trials

There will be new data from several previously reported trials focusing on specific groups of patients with type 2 diabetes. One is the EMPEROR-Preserved study of empagliflozin (Jardiance) in individuals with heart failure and preserved ejection fraction. Initially presented in August 2021 at the annual congress of the European Society of Cardiology, the new data will focus on patient subpopulations, efficacy endpoints, and safety in patients with and without diabetes. A companion study, EMPEROR-Reduced, in those with heart failure and reduced ejection fraction, was presented at the ESC Congress in August 2020.

New findings will also be presented from the DAPA-CKD study of dapagliflozin (Farxiga) in patients with chronic kidney disease. The study was stopped early in March 2020 because of overwhelming efficacy of the drug in preventing CKD. Now, the data will be analyzed in terms of metabolic, nephrology, and cardiology parameters.

And from FIDELIO-DKD and FIGARO-DKD, trials of the nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia), new data will also focus on a variety of subgroups of individuals with type 2 diabetes and chronic kidney disease.

“Our goal is to cover most aspects of what’s happening in the type 2 diabetes field,” EASD Honorary Secretary Mikael Rydén, MD, PhD, professor and senior consultant in endocrinology at the Karolinska Institute and Karolinska University Hospital, Stockholm, said in an interview.

Dr. Rydén, who chairs the meeting’s scientific program committee, added: “We can only focus on so much every year but we try to be active and changing from year to year. I’m convinced that a clinician or translational researcher will definitely have a number of very interesting symposia to follow and learn new things. If you follow all of these things, you will know a lot about what’s cooking in the diabetes world.”
 

Consensus on type 1 diabetes management: Special considerations

Both Dr. Del Prato and Dr. Rydén cited presentation of the new type 1 diabetes ADA/EASD consensus report as among the most clinically important of the conference. Initially presented in draft form at the ADA Scientific Sessions in June 2021, the document aims to move away from routinely applying principles derived from studies of patients with type 2 diabetes to those with type 1 diabetes, an autoimmune disease with unique characteristics.

The final version of the document is expected to include information on goals of therapy, glycemic targets, prevention and management of hypoglycemia and diabetic ketoacidosis, psychosocial care, and special populations, among other issues. It is also expected to include a section dedicated to adjunctive treatments beyond insulin, including metformin, pramlintide, glucagonlike peptide–1 agonists, and sodium-glucose cotransporter 2 inhibitors for certain patients.  

Dr. Del Prato noted, “From a clinical point of view, this is quite an important step that two major organizations came together recommending some strategies for treating type 2 diabetes ... It really deals with a big problem and tries to provide the tools for improving homogenization of the treatment of type 1 diabetes across the different health systems.”

And Dr. Rydén commented: “I think it’s really important to have, since there’s been so much focus on type 2 diabetes for the last few years, and to have the ADA and EASD getting together and actually write this.”

But Dr. Rydén also pointed out that outcomes data are much more conclusive for drugs in type 2 diabetes to inform international guidelines, whereas “this is much more difficult to demonstrate with type 1 diabetes. With a new pump or [continuous glucose monitor (CGM)] you might show a reduction in [hemoglobin] A1c of X percent or X mmol/mol or hypoglycemia events, but it’s much harder to show improvements in hard outcomes like deaths and cardiovascular events. I’m really looking forward to having this presented.”
 

Diabetes in 2021: It’s personal

Several meeting sessions will specifically address precision medicine approaches, including the TriMASTER study, which aims to identify subgroups of patients with type 2 diabetes who respond well or poorly to particular drugs based on clinical characteristics so that treatments can be better targeted to individuals. In total, 600 patients with type 2 diabetes and suboptimal glycemic control with metformin were randomized to a dipeptidyl peptidase–4 inhibitor, an SGLT2 inhibitor, or thiazolidinedione (TZD).

According to Dr. Rydén, “The TriMASTER final results will be interesting. TZDs still have a place. ... You can’t give them to people with heart failure, but I think like a carpenter you have to have many tools in your toolbox. And I still think that there are some individuals who respond well to pioglitazone. [The study findings] could be influential, depending on the results.”

An EASD/ADA symposium entitled “Optimizing diabetes diagnosis, prevention, and care: Is precision medicine the answer?” will offer three distinct perspectives, with one speaker arguing it’s the future of diabetes medicine, another that it isn’t, and a third explaining that “the devil is in the details.”

The Diabetologia symposium will focus on a related concept: The use of artificial intelligence in diabetes research and care, with particular application to glucose control, neuropathy, and wound healing.

And during the 36th Camillo Golgi Lecture, kidney disease expert H.J. Lambers Heerspink, PhD, of the University of Groningen (the Netherlands), will speak about personalizing treatment for patients with type 2 diabetes, arguing that “the mean is meaningless.”
 

Next-generation incretin therapy: Is weight loss the treatment?

New data will continue the buzz from the ADA meeting surrounding tirzepatide, the dual GLP-1 receptor agonist and glucose-dependent insulinotropic polypeptide agent.

A session will add new data from SURPASS-3 CGM, looking at the effect of the drug captured by continuous glucose monitoring in patients with type 2 diabetes; SURPASS-3 MRI, examining the effect of the drug on liver fat content and abdominal adipose tissue; and SURPASS-4, investigating efficacy and safety of tirzepatide once-weekly versus insulin glargine in patients with type 2 diabetes and increased cardiovascular risk.

The drug is notable for its dramatic reductions in both A1c and weight, although questions remain about the incidence of gastrointestinal side effects and effects on long-term cardiovascular and renal outcomes.

Dr. Rydén commented: “Given its effects on A1c and body weight, we would expect a positive result, but one never knows. It’s at least safe, that’s for sure. I think this mode of action is extremely interesting.”

Dr. Del Prato noted that tirzepatide could also “open up a new area of intervention for type 1 diabetes. The initial data were promising. ... It’s worth keeping an eye on.”

A related symposium will address the future of incretin-based treatments overall, while the EASD-Lancet symposium will examine whether the treatment of obesity is the «future» of diabetes treatment.
 

COVID-19, hypoglycemia, bone, and much more

As always, there’s much more on the agenda. Other noteworthy sessions include those addressing hypoglycemia management; a joint EASD/European Society of Endocrinology session on diabetes and bone; a debate about whether women with diabetes are at higher cardiovascular risk than men; and in-hospital management of hyperglycemia. 

A new feature of the meeting will be a daily roundup/wrap-up, where members of the program committee and speakers will summarize the day’s highlights. And another feature, “EASD e-Learning,” has been expanded to include more clinical topics around insulin use, nonalcoholic fatty liver disease, obesity, and neuropathy. 

Overall, Dr. Del Prato said, “it’s a very populated program, with more than 700 presenters, 162 invited symposia speakers, and 53 chairs. It’s covering widely different areas from basic to clinical research. ... It’s a lot of stuff going on.”

Both Dr. Rydén and Dr. Del Prato have disclosures with multiple manufacturers of diabetes-related products.

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

The annual meeting of the European Association for the Study of Diabetes 2021 will delve into individualized approaches in diabetes management, particularly with regard to tailoring drug therapy for type 2 diabetes and management of type 1 diabetes.  

Sara Freeman/MDedge News

The virtual meeting, taking place Sept. 28 to Oct. 1 in Central European Summer Time, will feature results from TriMASTER (a three-way cross-over trial of precision medicine strategy of second-/third-line therapy in type 2 diabetes), new subgroup analyses from the GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness) study, the final version of a consensus statement on type 1 diabetes management, and new data on the dual incretin agonist tirzepatide, as well as much more.

“I’m a strong believer in personalization. I don’t think the big blockbuster [drugs] will serve the entire community with diabetes. Even in type 1 diabetes, there’s evidence of heterogeneity. ... We need a better way to identify individual needs. I think that’s where we’re going. ... It’s one of the themes of the conference,” EASD President Stefano Del Prato, MD, professor of endocrinology at the University of Pisa (Italy), told this news organization.

He noted that EASD and the American Diabetes Association have recently teamed up with other organizations to form the Precision Medicine in Diabetes Initiative

As would be expected, the meeting will also feature numerous presentations on the COVID-19 pandemic, including studies looking at how people with COVID-19 and diabetes have fared; how the pandemic has affected diabetes care; and the still unclear impact of SARS-CoV-2 on pancreatic beta cells and whether, in some instances, it triggers new-onset diabetes.  
 

New data from previously reported trials

There will be new data from several previously reported trials focusing on specific groups of patients with type 2 diabetes. One is the EMPEROR-Preserved study of empagliflozin (Jardiance) in individuals with heart failure and preserved ejection fraction. Initially presented in August 2021 at the annual congress of the European Society of Cardiology, the new data will focus on patient subpopulations, efficacy endpoints, and safety in patients with and without diabetes. A companion study, EMPEROR-Reduced, in those with heart failure and reduced ejection fraction, was presented at the ESC Congress in August 2020.

New findings will also be presented from the DAPA-CKD study of dapagliflozin (Farxiga) in patients with chronic kidney disease. The study was stopped early in March 2020 because of overwhelming efficacy of the drug in preventing CKD. Now, the data will be analyzed in terms of metabolic, nephrology, and cardiology parameters.

And from FIDELIO-DKD and FIGARO-DKD, trials of the nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia), new data will also focus on a variety of subgroups of individuals with type 2 diabetes and chronic kidney disease.

“Our goal is to cover most aspects of what’s happening in the type 2 diabetes field,” EASD Honorary Secretary Mikael Rydén, MD, PhD, professor and senior consultant in endocrinology at the Karolinska Institute and Karolinska University Hospital, Stockholm, said in an interview.

Dr. Rydén, who chairs the meeting’s scientific program committee, added: “We can only focus on so much every year but we try to be active and changing from year to year. I’m convinced that a clinician or translational researcher will definitely have a number of very interesting symposia to follow and learn new things. If you follow all of these things, you will know a lot about what’s cooking in the diabetes world.”
 

Consensus on type 1 diabetes management: Special considerations

Both Dr. Del Prato and Dr. Rydén cited presentation of the new type 1 diabetes ADA/EASD consensus report as among the most clinically important of the conference. Initially presented in draft form at the ADA Scientific Sessions in June 2021, the document aims to move away from routinely applying principles derived from studies of patients with type 2 diabetes to those with type 1 diabetes, an autoimmune disease with unique characteristics.

The final version of the document is expected to include information on goals of therapy, glycemic targets, prevention and management of hypoglycemia and diabetic ketoacidosis, psychosocial care, and special populations, among other issues. It is also expected to include a section dedicated to adjunctive treatments beyond insulin, including metformin, pramlintide, glucagonlike peptide–1 agonists, and sodium-glucose cotransporter 2 inhibitors for certain patients.  

Dr. Del Prato noted, “From a clinical point of view, this is quite an important step that two major organizations came together recommending some strategies for treating type 2 diabetes ... It really deals with a big problem and tries to provide the tools for improving homogenization of the treatment of type 1 diabetes across the different health systems.”

And Dr. Rydén commented: “I think it’s really important to have, since there’s been so much focus on type 2 diabetes for the last few years, and to have the ADA and EASD getting together and actually write this.”

But Dr. Rydén also pointed out that outcomes data are much more conclusive for drugs in type 2 diabetes to inform international guidelines, whereas “this is much more difficult to demonstrate with type 1 diabetes. With a new pump or [continuous glucose monitor (CGM)] you might show a reduction in [hemoglobin] A1c of X percent or X mmol/mol or hypoglycemia events, but it’s much harder to show improvements in hard outcomes like deaths and cardiovascular events. I’m really looking forward to having this presented.”
 

Diabetes in 2021: It’s personal

Several meeting sessions will specifically address precision medicine approaches, including the TriMASTER study, which aims to identify subgroups of patients with type 2 diabetes who respond well or poorly to particular drugs based on clinical characteristics so that treatments can be better targeted to individuals. In total, 600 patients with type 2 diabetes and suboptimal glycemic control with metformin were randomized to a dipeptidyl peptidase–4 inhibitor, an SGLT2 inhibitor, or thiazolidinedione (TZD).

According to Dr. Rydén, “The TriMASTER final results will be interesting. TZDs still have a place. ... You can’t give them to people with heart failure, but I think like a carpenter you have to have many tools in your toolbox. And I still think that there are some individuals who respond well to pioglitazone. [The study findings] could be influential, depending on the results.”

An EASD/ADA symposium entitled “Optimizing diabetes diagnosis, prevention, and care: Is precision medicine the answer?” will offer three distinct perspectives, with one speaker arguing it’s the future of diabetes medicine, another that it isn’t, and a third explaining that “the devil is in the details.”

The Diabetologia symposium will focus on a related concept: The use of artificial intelligence in diabetes research and care, with particular application to glucose control, neuropathy, and wound healing.

And during the 36th Camillo Golgi Lecture, kidney disease expert H.J. Lambers Heerspink, PhD, of the University of Groningen (the Netherlands), will speak about personalizing treatment for patients with type 2 diabetes, arguing that “the mean is meaningless.”
 

Next-generation incretin therapy: Is weight loss the treatment?

New data will continue the buzz from the ADA meeting surrounding tirzepatide, the dual GLP-1 receptor agonist and glucose-dependent insulinotropic polypeptide agent.

A session will add new data from SURPASS-3 CGM, looking at the effect of the drug captured by continuous glucose monitoring in patients with type 2 diabetes; SURPASS-3 MRI, examining the effect of the drug on liver fat content and abdominal adipose tissue; and SURPASS-4, investigating efficacy and safety of tirzepatide once-weekly versus insulin glargine in patients with type 2 diabetes and increased cardiovascular risk.

The drug is notable for its dramatic reductions in both A1c and weight, although questions remain about the incidence of gastrointestinal side effects and effects on long-term cardiovascular and renal outcomes.

Dr. Rydén commented: “Given its effects on A1c and body weight, we would expect a positive result, but one never knows. It’s at least safe, that’s for sure. I think this mode of action is extremely interesting.”

Dr. Del Prato noted that tirzepatide could also “open up a new area of intervention for type 1 diabetes. The initial data were promising. ... It’s worth keeping an eye on.”

A related symposium will address the future of incretin-based treatments overall, while the EASD-Lancet symposium will examine whether the treatment of obesity is the «future» of diabetes treatment.
 

COVID-19, hypoglycemia, bone, and much more

As always, there’s much more on the agenda. Other noteworthy sessions include those addressing hypoglycemia management; a joint EASD/European Society of Endocrinology session on diabetes and bone; a debate about whether women with diabetes are at higher cardiovascular risk than men; and in-hospital management of hyperglycemia. 

A new feature of the meeting will be a daily roundup/wrap-up, where members of the program committee and speakers will summarize the day’s highlights. And another feature, “EASD e-Learning,” has been expanded to include more clinical topics around insulin use, nonalcoholic fatty liver disease, obesity, and neuropathy. 

Overall, Dr. Del Prato said, “it’s a very populated program, with more than 700 presenters, 162 invited symposia speakers, and 53 chairs. It’s covering widely different areas from basic to clinical research. ... It’s a lot of stuff going on.”

Both Dr. Rydén and Dr. Del Prato have disclosures with multiple manufacturers of diabetes-related products.

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

The annual meeting of the European Association for the Study of Diabetes 2021 will delve into individualized approaches in diabetes management, particularly with regard to tailoring drug therapy for type 2 diabetes and management of type 1 diabetes.  

Sara Freeman/MDedge News

The virtual meeting, taking place Sept. 28 to Oct. 1 in Central European Summer Time, will feature results from TriMASTER (a three-way cross-over trial of precision medicine strategy of second-/third-line therapy in type 2 diabetes), new subgroup analyses from the GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness) study, the final version of a consensus statement on type 1 diabetes management, and new data on the dual incretin agonist tirzepatide, as well as much more.

“I’m a strong believer in personalization. I don’t think the big blockbuster [drugs] will serve the entire community with diabetes. Even in type 1 diabetes, there’s evidence of heterogeneity. ... We need a better way to identify individual needs. I think that’s where we’re going. ... It’s one of the themes of the conference,” EASD President Stefano Del Prato, MD, professor of endocrinology at the University of Pisa (Italy), told this news organization.

He noted that EASD and the American Diabetes Association have recently teamed up with other organizations to form the Precision Medicine in Diabetes Initiative

As would be expected, the meeting will also feature numerous presentations on the COVID-19 pandemic, including studies looking at how people with COVID-19 and diabetes have fared; how the pandemic has affected diabetes care; and the still unclear impact of SARS-CoV-2 on pancreatic beta cells and whether, in some instances, it triggers new-onset diabetes.  
 

New data from previously reported trials

There will be new data from several previously reported trials focusing on specific groups of patients with type 2 diabetes. One is the EMPEROR-Preserved study of empagliflozin (Jardiance) in individuals with heart failure and preserved ejection fraction. Initially presented in August 2021 at the annual congress of the European Society of Cardiology, the new data will focus on patient subpopulations, efficacy endpoints, and safety in patients with and without diabetes. A companion study, EMPEROR-Reduced, in those with heart failure and reduced ejection fraction, was presented at the ESC Congress in August 2020.

New findings will also be presented from the DAPA-CKD study of dapagliflozin (Farxiga) in patients with chronic kidney disease. The study was stopped early in March 2020 because of overwhelming efficacy of the drug in preventing CKD. Now, the data will be analyzed in terms of metabolic, nephrology, and cardiology parameters.

And from FIDELIO-DKD and FIGARO-DKD, trials of the nonsteroidal mineralocorticoid receptor antagonist finerenone (Kerendia), new data will also focus on a variety of subgroups of individuals with type 2 diabetes and chronic kidney disease.

“Our goal is to cover most aspects of what’s happening in the type 2 diabetes field,” EASD Honorary Secretary Mikael Rydén, MD, PhD, professor and senior consultant in endocrinology at the Karolinska Institute and Karolinska University Hospital, Stockholm, said in an interview.

Dr. Rydén, who chairs the meeting’s scientific program committee, added: “We can only focus on so much every year but we try to be active and changing from year to year. I’m convinced that a clinician or translational researcher will definitely have a number of very interesting symposia to follow and learn new things. If you follow all of these things, you will know a lot about what’s cooking in the diabetes world.”
 

Consensus on type 1 diabetes management: Special considerations

Both Dr. Del Prato and Dr. Rydén cited presentation of the new type 1 diabetes ADA/EASD consensus report as among the most clinically important of the conference. Initially presented in draft form at the ADA Scientific Sessions in June 2021, the document aims to move away from routinely applying principles derived from studies of patients with type 2 diabetes to those with type 1 diabetes, an autoimmune disease with unique characteristics.

The final version of the document is expected to include information on goals of therapy, glycemic targets, prevention and management of hypoglycemia and diabetic ketoacidosis, psychosocial care, and special populations, among other issues. It is also expected to include a section dedicated to adjunctive treatments beyond insulin, including metformin, pramlintide, glucagonlike peptide–1 agonists, and sodium-glucose cotransporter 2 inhibitors for certain patients.  

Dr. Del Prato noted, “From a clinical point of view, this is quite an important step that two major organizations came together recommending some strategies for treating type 2 diabetes ... It really deals with a big problem and tries to provide the tools for improving homogenization of the treatment of type 1 diabetes across the different health systems.”

And Dr. Rydén commented: “I think it’s really important to have, since there’s been so much focus on type 2 diabetes for the last few years, and to have the ADA and EASD getting together and actually write this.”

But Dr. Rydén also pointed out that outcomes data are much more conclusive for drugs in type 2 diabetes to inform international guidelines, whereas “this is much more difficult to demonstrate with type 1 diabetes. With a new pump or [continuous glucose monitor (CGM)] you might show a reduction in [hemoglobin] A1c of X percent or X mmol/mol or hypoglycemia events, but it’s much harder to show improvements in hard outcomes like deaths and cardiovascular events. I’m really looking forward to having this presented.”
 

Diabetes in 2021: It’s personal

Several meeting sessions will specifically address precision medicine approaches, including the TriMASTER study, which aims to identify subgroups of patients with type 2 diabetes who respond well or poorly to particular drugs based on clinical characteristics so that treatments can be better targeted to individuals. In total, 600 patients with type 2 diabetes and suboptimal glycemic control with metformin were randomized to a dipeptidyl peptidase–4 inhibitor, an SGLT2 inhibitor, or thiazolidinedione (TZD).

According to Dr. Rydén, “The TriMASTER final results will be interesting. TZDs still have a place. ... You can’t give them to people with heart failure, but I think like a carpenter you have to have many tools in your toolbox. And I still think that there are some individuals who respond well to pioglitazone. [The study findings] could be influential, depending on the results.”

An EASD/ADA symposium entitled “Optimizing diabetes diagnosis, prevention, and care: Is precision medicine the answer?” will offer three distinct perspectives, with one speaker arguing it’s the future of diabetes medicine, another that it isn’t, and a third explaining that “the devil is in the details.”

The Diabetologia symposium will focus on a related concept: The use of artificial intelligence in diabetes research and care, with particular application to glucose control, neuropathy, and wound healing.

And during the 36th Camillo Golgi Lecture, kidney disease expert H.J. Lambers Heerspink, PhD, of the University of Groningen (the Netherlands), will speak about personalizing treatment for patients with type 2 diabetes, arguing that “the mean is meaningless.”
 

Next-generation incretin therapy: Is weight loss the treatment?

New data will continue the buzz from the ADA meeting surrounding tirzepatide, the dual GLP-1 receptor agonist and glucose-dependent insulinotropic polypeptide agent.

A session will add new data from SURPASS-3 CGM, looking at the effect of the drug captured by continuous glucose monitoring in patients with type 2 diabetes; SURPASS-3 MRI, examining the effect of the drug on liver fat content and abdominal adipose tissue; and SURPASS-4, investigating efficacy and safety of tirzepatide once-weekly versus insulin glargine in patients with type 2 diabetes and increased cardiovascular risk.

The drug is notable for its dramatic reductions in both A1c and weight, although questions remain about the incidence of gastrointestinal side effects and effects on long-term cardiovascular and renal outcomes.

Dr. Rydén commented: “Given its effects on A1c and body weight, we would expect a positive result, but one never knows. It’s at least safe, that’s for sure. I think this mode of action is extremely interesting.”

Dr. Del Prato noted that tirzepatide could also “open up a new area of intervention for type 1 diabetes. The initial data were promising. ... It’s worth keeping an eye on.”

A related symposium will address the future of incretin-based treatments overall, while the EASD-Lancet symposium will examine whether the treatment of obesity is the «future» of diabetes treatment.
 

COVID-19, hypoglycemia, bone, and much more

As always, there’s much more on the agenda. Other noteworthy sessions include those addressing hypoglycemia management; a joint EASD/European Society of Endocrinology session on diabetes and bone; a debate about whether women with diabetes are at higher cardiovascular risk than men; and in-hospital management of hyperglycemia. 

A new feature of the meeting will be a daily roundup/wrap-up, where members of the program committee and speakers will summarize the day’s highlights. And another feature, “EASD e-Learning,” has been expanded to include more clinical topics around insulin use, nonalcoholic fatty liver disease, obesity, and neuropathy. 

Overall, Dr. Del Prato said, “it’s a very populated program, with more than 700 presenters, 162 invited symposia speakers, and 53 chairs. It’s covering widely different areas from basic to clinical research. ... It’s a lot of stuff going on.”

Both Dr. Rydén and Dr. Del Prato have disclosures with multiple manufacturers of diabetes-related products.

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

At 18 months into the COVID-19 pandemic, many of the direct and indirect effects of SARS-CoV-2 on people with diabetes have become clearer, but knowledge gaps remain, say epidemiologists.

“COVID-19 has had a devastating effect on the population with diabetes, and conversely, the high prevalence of diabetes and uncontrolled diabetes has exacerbated the problem,” Edward W. Gregg, PhD, Imperial College London, lead author of a new literature review, told this news organization.

“As it becomes clear that the COVID-19 pandemic will be with us in different forms for the foreseeable future, the emphasis for people with diabetes needs to be continued primary care, glycemic management, and vaccination to reduce the long-term impact of COVID-19 in this population,” he added.

In data, mostly from case series, the review shows that more than one-third of people hospitalized with COVID-19 have diabetes. It is published in the September issue of Diabetes Care.

People with diabetes are more than three times as likely to be hospitalized for COVID-19 than those without diabetes, even after adjustment for age, sex, and other underlying conditions. Diabetes also accounts for 30%-40% of severe COVID-19 cases and deaths. Among those with diabetes hospitalized for COVID-19, 21%-43% require intensive care, and the case fatality rate is about 25%.

In one of the few multivariate analyses that examined type 1 and type 2 diabetes separately, conducted in the U.K., the odds of in-hospital COVID-19–related deaths, compared with people without diabetes, were almost three times higher (odds ratio, 2.9) for individuals with type 1 diabetes and almost twice as high (OR, 1.8) for those with type 2, after adjustment for comorbidities.

The causes of death appear to be a combination of factors specific to the SARS-CoV-2 infection and to diabetes-related factors, Dr. Gregg said in an interview.

“Much of the increased risk is due to the fact that people with diabetes have more comorbid factors, but there are many other mechanisms that appear to further increase risk, including the inflammatory and immune responses of people with diabetes, and hyperglycemia appears to have an exacerbating effect by itself.”
 

Elevated glucose is clear risk factor for COVID-19 severity

Elevated A1c was identified among several other overall predictors of poor COVID-19 outcomes, including obesity as well as comorbid kidney and cardiovascular disease.

High blood glucose levels at the time of admission in people with previously diagnosed or undiagnosed diabetes emerged as a clear predictor of worse outcomes. For example, among 605 people hospitalized with COVID-19 in China, those with fasting plasma glucose 6.1-6.9 mmol/L (110-125 mg/dL) and ≥7 mmol/L (126 mg/dL) had odds ratios of poor outcomes within 28 days of 2.6 and 4.0 compared with FPG <6.1 mmol/L (110 mg/dL).

Population-based studies in the U.K. found that A1c levels measured months before COVID-19 hospitalization were associated with risk for intensive care unit admission and/or death, particularly among those with type 1 diabetes. Overall, the death rate was 36% higher for those with A1c of 9%-9.9% versus 6.5%-7%.

Despite the link between high A1c and death, there is as yet no clear evidence that normalizing blood glucose levels minimizes COVID-19 severity, Dr. Gregg said.

“There are data that suggest poor glycemic control is associated with higher risk of poor outcomes. This is indirect evidence that managing blood sugar will help, but more direct evidence is needed.”
 

Evidence gaps identified

Dr. Gregg and co-authors Marisa Sophiea, PhD, MSc, and Misghina Weldegiorgis, PhD, BSc, also from Imperial College London, identify three areas in which more data are needed.

First, more information is needed to determine whether exposure, infection, and hospitalization risks differ by diabetes status and how those factors affect outcomes. The same studies would also be important to identify how factors such as behavior, masking, and lockdown policies, risk factor control, and household/community environments affect risk in people with diabetes.

Second, studies are needed to better understand indirect effects of the pandemic, such as care and management factors. Some of these, such as the advent of telehealth, may turn out to be beneficial in the long run, they note.

Finally, the pandemic has “brought a wealth of natural experiments,” such as how vaccination programs and other interventions are affecting people with diabetes specifically. Finally, population studies are needed in many parts of the world beyond the U.S. and the U.K., where most of that work has been done thus far.

“Many of the most important unanswered questions lie in the potential indirect and long-term impact of the pandemic that require population-based studies,” Dr. Gregg said. “Most of our knowledge so far is from case series, which only assess patients from the time of hospitalization.”

Indeed, very little data are available for people with diabetes who get COVID-19 but are not hospitalized, so it’s not known whether they have a longer duration of illness or are at greater risk for “long COVID” than those without diabetes who experience COVID-19 at home.

“I have not seen published data on this yet, and it’s an important unanswered question,” Dr. Gregg said.  

The authors have disclosed no relevant financial relationships.

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

At 18 months into the COVID-19 pandemic, many of the direct and indirect effects of SARS-CoV-2 on people with diabetes have become clearer, but knowledge gaps remain, say epidemiologists.

“COVID-19 has had a devastating effect on the population with diabetes, and conversely, the high prevalence of diabetes and uncontrolled diabetes has exacerbated the problem,” Edward W. Gregg, PhD, Imperial College London, lead author of a new literature review, told this news organization.

“As it becomes clear that the COVID-19 pandemic will be with us in different forms for the foreseeable future, the emphasis for people with diabetes needs to be continued primary care, glycemic management, and vaccination to reduce the long-term impact of COVID-19 in this population,” he added.

In data, mostly from case series, the review shows that more than one-third of people hospitalized with COVID-19 have diabetes. It is published in the September issue of Diabetes Care.

People with diabetes are more than three times as likely to be hospitalized for COVID-19 than those without diabetes, even after adjustment for age, sex, and other underlying conditions. Diabetes also accounts for 30%-40% of severe COVID-19 cases and deaths. Among those with diabetes hospitalized for COVID-19, 21%-43% require intensive care, and the case fatality rate is about 25%.

In one of the few multivariate analyses that examined type 1 and type 2 diabetes separately, conducted in the U.K., the odds of in-hospital COVID-19–related deaths, compared with people without diabetes, were almost three times higher (odds ratio, 2.9) for individuals with type 1 diabetes and almost twice as high (OR, 1.8) for those with type 2, after adjustment for comorbidities.

The causes of death appear to be a combination of factors specific to the SARS-CoV-2 infection and to diabetes-related factors, Dr. Gregg said in an interview.

“Much of the increased risk is due to the fact that people with diabetes have more comorbid factors, but there are many other mechanisms that appear to further increase risk, including the inflammatory and immune responses of people with diabetes, and hyperglycemia appears to have an exacerbating effect by itself.”
 

Elevated glucose is clear risk factor for COVID-19 severity

Elevated A1c was identified among several other overall predictors of poor COVID-19 outcomes, including obesity as well as comorbid kidney and cardiovascular disease.

High blood glucose levels at the time of admission in people with previously diagnosed or undiagnosed diabetes emerged as a clear predictor of worse outcomes. For example, among 605 people hospitalized with COVID-19 in China, those with fasting plasma glucose 6.1-6.9 mmol/L (110-125 mg/dL) and ≥7 mmol/L (126 mg/dL) had odds ratios of poor outcomes within 28 days of 2.6 and 4.0 compared with FPG <6.1 mmol/L (110 mg/dL).

Population-based studies in the U.K. found that A1c levels measured months before COVID-19 hospitalization were associated with risk for intensive care unit admission and/or death, particularly among those with type 1 diabetes. Overall, the death rate was 36% higher for those with A1c of 9%-9.9% versus 6.5%-7%.

Despite the link between high A1c and death, there is as yet no clear evidence that normalizing blood glucose levels minimizes COVID-19 severity, Dr. Gregg said.

“There are data that suggest poor glycemic control is associated with higher risk of poor outcomes. This is indirect evidence that managing blood sugar will help, but more direct evidence is needed.”
 

Evidence gaps identified

Dr. Gregg and co-authors Marisa Sophiea, PhD, MSc, and Misghina Weldegiorgis, PhD, BSc, also from Imperial College London, identify three areas in which more data are needed.

First, more information is needed to determine whether exposure, infection, and hospitalization risks differ by diabetes status and how those factors affect outcomes. The same studies would also be important to identify how factors such as behavior, masking, and lockdown policies, risk factor control, and household/community environments affect risk in people with diabetes.

Second, studies are needed to better understand indirect effects of the pandemic, such as care and management factors. Some of these, such as the advent of telehealth, may turn out to be beneficial in the long run, they note.

Finally, the pandemic has “brought a wealth of natural experiments,” such as how vaccination programs and other interventions are affecting people with diabetes specifically. Finally, population studies are needed in many parts of the world beyond the U.S. and the U.K., where most of that work has been done thus far.

“Many of the most important unanswered questions lie in the potential indirect and long-term impact of the pandemic that require population-based studies,” Dr. Gregg said. “Most of our knowledge so far is from case series, which only assess patients from the time of hospitalization.”

Indeed, very little data are available for people with diabetes who get COVID-19 but are not hospitalized, so it’s not known whether they have a longer duration of illness or are at greater risk for “long COVID” than those without diabetes who experience COVID-19 at home.

“I have not seen published data on this yet, and it’s an important unanswered question,” Dr. Gregg said.  

The authors have disclosed no relevant financial relationships.

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

At 18 months into the COVID-19 pandemic, many of the direct and indirect effects of SARS-CoV-2 on people with diabetes have become clearer, but knowledge gaps remain, say epidemiologists.

“COVID-19 has had a devastating effect on the population with diabetes, and conversely, the high prevalence of diabetes and uncontrolled diabetes has exacerbated the problem,” Edward W. Gregg, PhD, Imperial College London, lead author of a new literature review, told this news organization.

“As it becomes clear that the COVID-19 pandemic will be with us in different forms for the foreseeable future, the emphasis for people with diabetes needs to be continued primary care, glycemic management, and vaccination to reduce the long-term impact of COVID-19 in this population,” he added.

In data, mostly from case series, the review shows that more than one-third of people hospitalized with COVID-19 have diabetes. It is published in the September issue of Diabetes Care.

People with diabetes are more than three times as likely to be hospitalized for COVID-19 than those without diabetes, even after adjustment for age, sex, and other underlying conditions. Diabetes also accounts for 30%-40% of severe COVID-19 cases and deaths. Among those with diabetes hospitalized for COVID-19, 21%-43% require intensive care, and the case fatality rate is about 25%.

In one of the few multivariate analyses that examined type 1 and type 2 diabetes separately, conducted in the U.K., the odds of in-hospital COVID-19–related deaths, compared with people without diabetes, were almost three times higher (odds ratio, 2.9) for individuals with type 1 diabetes and almost twice as high (OR, 1.8) for those with type 2, after adjustment for comorbidities.

The causes of death appear to be a combination of factors specific to the SARS-CoV-2 infection and to diabetes-related factors, Dr. Gregg said in an interview.

“Much of the increased risk is due to the fact that people with diabetes have more comorbid factors, but there are many other mechanisms that appear to further increase risk, including the inflammatory and immune responses of people with diabetes, and hyperglycemia appears to have an exacerbating effect by itself.”
 

Elevated glucose is clear risk factor for COVID-19 severity

Elevated A1c was identified among several other overall predictors of poor COVID-19 outcomes, including obesity as well as comorbid kidney and cardiovascular disease.

High blood glucose levels at the time of admission in people with previously diagnosed or undiagnosed diabetes emerged as a clear predictor of worse outcomes. For example, among 605 people hospitalized with COVID-19 in China, those with fasting plasma glucose 6.1-6.9 mmol/L (110-125 mg/dL) and ≥7 mmol/L (126 mg/dL) had odds ratios of poor outcomes within 28 days of 2.6 and 4.0 compared with FPG <6.1 mmol/L (110 mg/dL).

Population-based studies in the U.K. found that A1c levels measured months before COVID-19 hospitalization were associated with risk for intensive care unit admission and/or death, particularly among those with type 1 diabetes. Overall, the death rate was 36% higher for those with A1c of 9%-9.9% versus 6.5%-7%.

Despite the link between high A1c and death, there is as yet no clear evidence that normalizing blood glucose levels minimizes COVID-19 severity, Dr. Gregg said.

“There are data that suggest poor glycemic control is associated with higher risk of poor outcomes. This is indirect evidence that managing blood sugar will help, but more direct evidence is needed.”
 

Evidence gaps identified

Dr. Gregg and co-authors Marisa Sophiea, PhD, MSc, and Misghina Weldegiorgis, PhD, BSc, also from Imperial College London, identify three areas in which more data are needed.

First, more information is needed to determine whether exposure, infection, and hospitalization risks differ by diabetes status and how those factors affect outcomes. The same studies would also be important to identify how factors such as behavior, masking, and lockdown policies, risk factor control, and household/community environments affect risk in people with diabetes.

Second, studies are needed to better understand indirect effects of the pandemic, such as care and management factors. Some of these, such as the advent of telehealth, may turn out to be beneficial in the long run, they note.

Finally, the pandemic has “brought a wealth of natural experiments,” such as how vaccination programs and other interventions are affecting people with diabetes specifically. Finally, population studies are needed in many parts of the world beyond the U.S. and the U.K., where most of that work has been done thus far.

“Many of the most important unanswered questions lie in the potential indirect and long-term impact of the pandemic that require population-based studies,” Dr. Gregg said. “Most of our knowledge so far is from case series, which only assess patients from the time of hospitalization.”

Indeed, very little data are available for people with diabetes who get COVID-19 but are not hospitalized, so it’s not known whether they have a longer duration of illness or are at greater risk for “long COVID” than those without diabetes who experience COVID-19 at home.

“I have not seen published data on this yet, and it’s an important unanswered question,” Dr. Gregg said.  

The authors have disclosed no relevant financial relationships.

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

A new joint consensus statement by four major diabetes organizations aims to standardize the terminology, definition, and assessment to the phenomenon of diabetes “remission.”

The statement was jointly issued by the American Diabetes Association, the Endocrine Society, the European Association for the Study of Diabetes, and Diabetes UK.

The 12-member international writing panel proposed use of the term “remission,” as opposed to others such as “reversal,” “resolution,” or “cure,” to describe the phenomenon of prolonged normoglycemia without the use of glucose-lowering medication in a person previously diagnosed with type 2 diabetes.

“Diabetes remission may be occurring more often due to advances in treatment,” writing group member Amy Rothberg, MD, of the University of Michigan, Ann Arbor, said in a statement.

The group defined “remission” – whether attained via lifestyle, bariatric surgery, or other means – as an A1c < 6.5% (< 48 mmol/mol) at least 3 months after cessation of glucose-lowering pharmacotherapy. The panel also suggested monitoring individuals experiencing diabetes remission and raised questions that need further attention and study.

But it’s not a guideline, panel chair Matthew C. Riddle, MD, said in an interview. Rather, the “main purpose of the statement was to provide definitions, terminology, cut-points, and timing recommendations to allow data collection that will eventually lead to clinical guidelines,” he said.

A great deal of epidemiological research is conducted by analyzing data from medical records, he noted. “If clinicians are more consistent in entering data into the records and in doing measurements, it will be a better database.”
 

Remission reality: Advice needed for deprescribing, talking to patients

“Increasingly our treatments are getting glucose levels into the normal range, and in many cases, even after withdrawal of drug therapy. That’s not an anomaly or a fiction, it’s reality. Clinicians need to know how to talk to their patients about it,” noted Dr. Riddle, of the division of endocrinology, diabetes, and clinical nutrition at Oregon Health & Science University, Portland.

There is a need for data on the effects of deprescribing once normoglycemia is achieved, he said. “It really goes a long way to have strong epidemiological and interventional evidence. That’s what we need here, and that’s what the group is really hoping for.”

The statement recommends the following:

• The term “remission” should be used to describe a sustained metabolic improvement in type 2 diabetes to near normal levels. The panel agreed the word strikes the best balance, given that insulin resistance and beta-cell dysfunction may still be present despite normoglycemia. “Diabetes doesn’t get cured. The underlying abnormalities are still there. Remission is defined by glucose,” Dr. Riddle said. The panel also decided to do away with ADA’s former terms “partial,” “complete,” and “prolonged” remission because they are ambiguous and unhelpful. 
• Remission should be defined as a return to an A1c of < 6.5% (< 48 mmol/mol) – the threshold used to diagnose diabetes – spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering medication.
• When A1c may be unreliable, such as conditions involving variant hemoglobin or erythrocyte survival alterations, acceptable alternatives are a fasting blood glucose < 126 mg/dL (< 7.0 mmol/L) or an estimated A1c < 6.5% calculated from continuous glucose monitoring data.
• A1c testing to document a remission should be performed just prior to an intervention and no sooner than 3 months after initiation of the intervention and withdrawal of any glucose-lowering medication.
• Subsequent ongoing A1c testing should be done at least yearly thereafter, along with routine monitoring for diabetes-related complications, including retinal screening, renal function assessment, foot exams, and cardiovascular risk factor testing. “At present, there is no long-term evidence indicating that any of the usually recommended assessments for complications can safely be discontinued,” the authors wrote.
• Research based on the terminology and definitions in the present statement is needed to determine the frequency, duration, and effects on short- and long-term medical outcomes of type 2 diabetes remissions using available interventions.

Dr. Riddle said in an interview: “We thought that the clinical community needed to understand where this issue stands right now. The feasibility of a remission is greater than it used to be.

“We’re going to see more patients who have what we can now call a remission according to a standardized definition. In the future, there are likely to be guidelines regarding the kind of patients and the kind of tactics appropriate for seeking a remission,” he said.

The statement was simultaneously published online in each of the organizations’ respective journals: Diabetes Care, Journal of Clinical Endocrinology & Metabolism, Diabetologia, and Diabetic Medicine.

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from Eli Lilly, Novo Nordisk, and AstraZeneca and honoraria for consulting from Adocia, Intercept, and Theracos.

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

A new joint consensus statement by four major diabetes organizations aims to standardize the terminology, definition, and assessment to the phenomenon of diabetes “remission.”

The statement was jointly issued by the American Diabetes Association, the Endocrine Society, the European Association for the Study of Diabetes, and Diabetes UK.

The 12-member international writing panel proposed use of the term “remission,” as opposed to others such as “reversal,” “resolution,” or “cure,” to describe the phenomenon of prolonged normoglycemia without the use of glucose-lowering medication in a person previously diagnosed with type 2 diabetes.

“Diabetes remission may be occurring more often due to advances in treatment,” writing group member Amy Rothberg, MD, of the University of Michigan, Ann Arbor, said in a statement.

The group defined “remission” – whether attained via lifestyle, bariatric surgery, or other means – as an A1c < 6.5% (< 48 mmol/mol) at least 3 months after cessation of glucose-lowering pharmacotherapy. The panel also suggested monitoring individuals experiencing diabetes remission and raised questions that need further attention and study.

But it’s not a guideline, panel chair Matthew C. Riddle, MD, said in an interview. Rather, the “main purpose of the statement was to provide definitions, terminology, cut-points, and timing recommendations to allow data collection that will eventually lead to clinical guidelines,” he said.

A great deal of epidemiological research is conducted by analyzing data from medical records, he noted. “If clinicians are more consistent in entering data into the records and in doing measurements, it will be a better database.”
 

Remission reality: Advice needed for deprescribing, talking to patients

“Increasingly our treatments are getting glucose levels into the normal range, and in many cases, even after withdrawal of drug therapy. That’s not an anomaly or a fiction, it’s reality. Clinicians need to know how to talk to their patients about it,” noted Dr. Riddle, of the division of endocrinology, diabetes, and clinical nutrition at Oregon Health & Science University, Portland.

There is a need for data on the effects of deprescribing once normoglycemia is achieved, he said. “It really goes a long way to have strong epidemiological and interventional evidence. That’s what we need here, and that’s what the group is really hoping for.”

The statement recommends the following:

• The term “remission” should be used to describe a sustained metabolic improvement in type 2 diabetes to near normal levels. The panel agreed the word strikes the best balance, given that insulin resistance and beta-cell dysfunction may still be present despite normoglycemia. “Diabetes doesn’t get cured. The underlying abnormalities are still there. Remission is defined by glucose,” Dr. Riddle said. The panel also decided to do away with ADA’s former terms “partial,” “complete,” and “prolonged” remission because they are ambiguous and unhelpful. 
• Remission should be defined as a return to an A1c of < 6.5% (< 48 mmol/mol) – the threshold used to diagnose diabetes – spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering medication.
• When A1c may be unreliable, such as conditions involving variant hemoglobin or erythrocyte survival alterations, acceptable alternatives are a fasting blood glucose < 126 mg/dL (< 7.0 mmol/L) or an estimated A1c < 6.5% calculated from continuous glucose monitoring data.
• A1c testing to document a remission should be performed just prior to an intervention and no sooner than 3 months after initiation of the intervention and withdrawal of any glucose-lowering medication.
• Subsequent ongoing A1c testing should be done at least yearly thereafter, along with routine monitoring for diabetes-related complications, including retinal screening, renal function assessment, foot exams, and cardiovascular risk factor testing. “At present, there is no long-term evidence indicating that any of the usually recommended assessments for complications can safely be discontinued,” the authors wrote.
• Research based on the terminology and definitions in the present statement is needed to determine the frequency, duration, and effects on short- and long-term medical outcomes of type 2 diabetes remissions using available interventions.

Dr. Riddle said in an interview: “We thought that the clinical community needed to understand where this issue stands right now. The feasibility of a remission is greater than it used to be.

“We’re going to see more patients who have what we can now call a remission according to a standardized definition. In the future, there are likely to be guidelines regarding the kind of patients and the kind of tactics appropriate for seeking a remission,” he said.

The statement was simultaneously published online in each of the organizations’ respective journals: Diabetes Care, Journal of Clinical Endocrinology & Metabolism, Diabetologia, and Diabetic Medicine.

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from Eli Lilly, Novo Nordisk, and AstraZeneca and honoraria for consulting from Adocia, Intercept, and Theracos.

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

A new joint consensus statement by four major diabetes organizations aims to standardize the terminology, definition, and assessment to the phenomenon of diabetes “remission.”

The statement was jointly issued by the American Diabetes Association, the Endocrine Society, the European Association for the Study of Diabetes, and Diabetes UK.

The 12-member international writing panel proposed use of the term “remission,” as opposed to others such as “reversal,” “resolution,” or “cure,” to describe the phenomenon of prolonged normoglycemia without the use of glucose-lowering medication in a person previously diagnosed with type 2 diabetes.

“Diabetes remission may be occurring more often due to advances in treatment,” writing group member Amy Rothberg, MD, of the University of Michigan, Ann Arbor, said in a statement.

The group defined “remission” – whether attained via lifestyle, bariatric surgery, or other means – as an A1c < 6.5% (< 48 mmol/mol) at least 3 months after cessation of glucose-lowering pharmacotherapy. The panel also suggested monitoring individuals experiencing diabetes remission and raised questions that need further attention and study.

But it’s not a guideline, panel chair Matthew C. Riddle, MD, said in an interview. Rather, the “main purpose of the statement was to provide definitions, terminology, cut-points, and timing recommendations to allow data collection that will eventually lead to clinical guidelines,” he said.

A great deal of epidemiological research is conducted by analyzing data from medical records, he noted. “If clinicians are more consistent in entering data into the records and in doing measurements, it will be a better database.”
 

Remission reality: Advice needed for deprescribing, talking to patients

“Increasingly our treatments are getting glucose levels into the normal range, and in many cases, even after withdrawal of drug therapy. That’s not an anomaly or a fiction, it’s reality. Clinicians need to know how to talk to their patients about it,” noted Dr. Riddle, of the division of endocrinology, diabetes, and clinical nutrition at Oregon Health & Science University, Portland.

There is a need for data on the effects of deprescribing once normoglycemia is achieved, he said. “It really goes a long way to have strong epidemiological and interventional evidence. That’s what we need here, and that’s what the group is really hoping for.”

The statement recommends the following:

• The term “remission” should be used to describe a sustained metabolic improvement in type 2 diabetes to near normal levels. The panel agreed the word strikes the best balance, given that insulin resistance and beta-cell dysfunction may still be present despite normoglycemia. “Diabetes doesn’t get cured. The underlying abnormalities are still there. Remission is defined by glucose,” Dr. Riddle said. The panel also decided to do away with ADA’s former terms “partial,” “complete,” and “prolonged” remission because they are ambiguous and unhelpful. 
• Remission should be defined as a return to an A1c of < 6.5% (< 48 mmol/mol) – the threshold used to diagnose diabetes – spontaneously or following an intervention and that persists for at least 3 months in the absence of usual glucose-lowering medication.
• When A1c may be unreliable, such as conditions involving variant hemoglobin or erythrocyte survival alterations, acceptable alternatives are a fasting blood glucose < 126 mg/dL (< 7.0 mmol/L) or an estimated A1c < 6.5% calculated from continuous glucose monitoring data.
• A1c testing to document a remission should be performed just prior to an intervention and no sooner than 3 months after initiation of the intervention and withdrawal of any glucose-lowering medication.
• Subsequent ongoing A1c testing should be done at least yearly thereafter, along with routine monitoring for diabetes-related complications, including retinal screening, renal function assessment, foot exams, and cardiovascular risk factor testing. “At present, there is no long-term evidence indicating that any of the usually recommended assessments for complications can safely be discontinued,” the authors wrote.
• Research based on the terminology and definitions in the present statement is needed to determine the frequency, duration, and effects on short- and long-term medical outcomes of type 2 diabetes remissions using available interventions.

Dr. Riddle said in an interview: “We thought that the clinical community needed to understand where this issue stands right now. The feasibility of a remission is greater than it used to be.

“We’re going to see more patients who have what we can now call a remission according to a standardized definition. In the future, there are likely to be guidelines regarding the kind of patients and the kind of tactics appropriate for seeking a remission,” he said.

The statement was simultaneously published online in each of the organizations’ respective journals: Diabetes Care, Journal of Clinical Endocrinology & Metabolism, Diabetologia, and Diabetic Medicine.

Dr. Riddle has reported receiving research grant support through Oregon Health & Science University from Eli Lilly, Novo Nordisk, and AstraZeneca and honoraria for consulting from Adocia, Intercept, and Theracos.

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