Investigational Insulin Analogue Effective, Safe in Early Trials

ORLANDO — A novel investigational ultra–long-acting insulin analogue produced glycemic control similar to insulin glargine when injected once daily or three times weekly, with better postdinner control.

The analogue, insulin degludec, forms soluble multihexamer depots after subcutaneous injection, resulting in a longer duration of action than any available insulin analogue. Novo Nordisk is developing two formulations, one of degludec alone and the other a 70/30 combination with the short-acting insulin aspart. There is no 70/30 formulation on the market that includes a basal insulin, Dr. Bernard Zinman said in an interview.

Data from two phase II proof-of-concept trials presented at the scientific sessions suggest that insulin degludec provides glucose control comparable to regimens using available basal insulins, with the advantages of fewer injections, better postdinner control, and possibly less hypoglycemia.

Dr. Zinman, professor of medicine and director of the Leadership Sinai Centre for Diabetes at the University of Toronto, reported on a 16-week, open-label, parallel-group, treat-to-target trial in which 245 patients with type 2 diabetes that was inadequately controlled by oral agents were randomized to one of four arms: the 70/30 formulation; a once-daily 55/45 formulation, which has since been discontinued; a three-times-weekly formulation (Monday, Wednesday, and Friday); or insulin glargine. All insulins were injected in the evening and titrated to target a fasting plasma glucose (FPG) of 72-108 mg/dL. All patients also continued taking metformin.

At baseline, the patients had a mean age of 54 years, mean hemoglobin A_1c of 8.7%, mean FPG of 184 mg/dL, and mean body mass index of 29.5 kg/m

After 16 weeks, reduction in HbA_1c from baseline was similar across treatment arms, with drops of 1.3 percentage points with once-daily insulin degludec, 1.5 points with thrice-weekly degludec, and 1.5 points with insulin glargine. Final mean HbA_1c also did not differ between groups, at 7.4% for once-daily degludec, 7.3% for the thrice-weekly version, and 7.2% for insulin glargine. Results for the 55/45 formulation were not reported.

FPG reductions were similar, as were final mean FPG (113, 116, and 115 mg/dL). Mean weekly insulin doses were similar at the end of the trial.

Rates of confirmed hypoglycemia(plasma glucose value of less than 56 mg/dL or requiring assistance) were low and only one severe event was reported (for thrice-weekly degludec). The rate of confirmed hypoglycemia was lower with once-daily degludec than with the thrice-weekly formulation and glargine, but the differences were not statistically significant (0.6, 2.3, 1.1 events per patient-year, respectively).

The proportion of subjects with adverse events did not differ significantly across treatment arms, with no specific patterns or clustering. Most adverse events were mild or moderate in severity, he said.

Dr. Tim Heise, CEO of the Profil Institute for Metabolic Research Ltd., Neuss, Germany, presented the data on the 70/30 degludec-aspart combination (IDegAsp). This 16-week open-label, parallel-group, treat-to-target trial randomized 178 patients who were inadequately controlled on oral agents to receive either once-daily 70/30 IDegAsp, the alternate 55/45 combination, or insulin glargine, all in combination with metformin. (Because the 55/45 combination has been discontinued, reports for that group are not available.)

Both insulins were dosed before dinner and titrated to an FPG target of 72-108 mg/dL. The patients had a mean age of 59 years, HbA_1c of 8.5%, and FPG of 209 mg/dL. After 16 weeks, mean HbA_1c decreased from baseline in both treatment groups, by 1.31 percentage points with IDegAsp and by 1.29 with insulin glargine. HbA_1c values were comparable: 7.0% for IDegAsp and 7.1% for insulin glargine. The proportions achieving HbA_1c values of less than 7.0% without confirmed hypoglycemia were 51% for IDegAsp and 50% with glargine, Dr. Heise reported.

The mean increase in plasma glucose at 2 hours after dinner was significantly lower for degludec than for glargine (2 mg/dL for IDegAsp versus 29 mg/dL with glargine), while FPG was similar between groups (122 and 126 mg/dL, respectively). At the trial's end, mean daily insulin doses were lower for IDegAsp than for insulin glargine.

No severe hypoglycemic events were reported. Rates of confirmed hypoglycemia (PG less than 56 mg/dL) were lower for IDegAsp and glargine than for the 55/45 version (1.2, 0.7, and 2.4 events per patient-year, respectively). One confirmed nocturnal hypoglycemic event was reported for IDegAsp in one patient and three events were reported in three patients on insulin glargine. No other adverse events were reported.

This study was funded by Novo Nordisk, which is now proceeding with phase III trials of insulin degludec.

Dr. Zinman's and Dr. Heise's institution receive research funding from manufacturers of diabetes-related products. Dr. Zinman has financial ties with GlaxoSmithKline, Merck, Amylin Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc., Eli Lilly and Co., and Medtronic Minimed. Dr. Heise serves on an advisory panel for Novo Nordisk.

At the trial's end, mean daily insulin doses were lower for the analogue than for glargine.

Source DR. HEISE

ORLANDO — A novel investigational ultra–long-acting insulin analogue produced glycemic control similar to insulin glargine when injected once daily or three times weekly, with better postdinner control.

The analogue, insulin degludec, forms soluble multihexamer depots after subcutaneous injection, resulting in a longer duration of action than any available insulin analogue. Novo Nordisk is developing two formulations, one of degludec alone and the other a 70/30 combination with the short-acting insulin aspart. There is no 70/30 formulation on the market that includes a basal insulin, Dr. Bernard Zinman said in an interview.

Data from two phase II proof-of-concept trials presented at the scientific sessions suggest that insulin degludec provides glucose control comparable to regimens using available basal insulins, with the advantages of fewer injections, better postdinner control, and possibly less hypoglycemia.

Dr. Zinman, professor of medicine and director of the Leadership Sinai Centre for Diabetes at the University of Toronto, reported on a 16-week, open-label, parallel-group, treat-to-target trial in which 245 patients with type 2 diabetes that was inadequately controlled by oral agents were randomized to one of four arms: the 70/30 formulation; a once-daily 55/45 formulation, which has since been discontinued; a three-times-weekly formulation (Monday, Wednesday, and Friday); or insulin glargine. All insulins were injected in the evening and titrated to target a fasting plasma glucose (FPG) of 72-108 mg/dL. All patients also continued taking metformin.

At baseline, the patients had a mean age of 54 years, mean hemoglobin A_1c of 8.7%, mean FPG of 184 mg/dL, and mean body mass index of 29.5 kg/m

After 16 weeks, reduction in HbA_1c from baseline was similar across treatment arms, with drops of 1.3 percentage points with once-daily insulin degludec, 1.5 points with thrice-weekly degludec, and 1.5 points with insulin glargine. Final mean HbA_1c also did not differ between groups, at 7.4% for once-daily degludec, 7.3% for the thrice-weekly version, and 7.2% for insulin glargine. Results for the 55/45 formulation were not reported.

FPG reductions were similar, as were final mean FPG (113, 116, and 115 mg/dL). Mean weekly insulin doses were similar at the end of the trial.

Rates of confirmed hypoglycemia(plasma glucose value of less than 56 mg/dL or requiring assistance) were low and only one severe event was reported (for thrice-weekly degludec). The rate of confirmed hypoglycemia was lower with once-daily degludec than with the thrice-weekly formulation and glargine, but the differences were not statistically significant (0.6, 2.3, 1.1 events per patient-year, respectively).

The proportion of subjects with adverse events did not differ significantly across treatment arms, with no specific patterns or clustering. Most adverse events were mild or moderate in severity, he said.

Dr. Tim Heise, CEO of the Profil Institute for Metabolic Research Ltd., Neuss, Germany, presented the data on the 70/30 degludec-aspart combination (IDegAsp). This 16-week open-label, parallel-group, treat-to-target trial randomized 178 patients who were inadequately controlled on oral agents to receive either once-daily 70/30 IDegAsp, the alternate 55/45 combination, or insulin glargine, all in combination with metformin. (Because the 55/45 combination has been discontinued, reports for that group are not available.)

Both insulins were dosed before dinner and titrated to an FPG target of 72-108 mg/dL. The patients had a mean age of 59 years, HbA_1c of 8.5%, and FPG of 209 mg/dL. After 16 weeks, mean HbA_1c decreased from baseline in both treatment groups, by 1.31 percentage points with IDegAsp and by 1.29 with insulin glargine. HbA_1c values were comparable: 7.0% for IDegAsp and 7.1% for insulin glargine. The proportions achieving HbA_1c values of less than 7.0% without confirmed hypoglycemia were 51% for IDegAsp and 50% with glargine, Dr. Heise reported.

The mean increase in plasma glucose at 2 hours after dinner was significantly lower for degludec than for glargine (2 mg/dL for IDegAsp versus 29 mg/dL with glargine), while FPG was similar between groups (122 and 126 mg/dL, respectively). At the trial's end, mean daily insulin doses were lower for IDegAsp than for insulin glargine.

No severe hypoglycemic events were reported. Rates of confirmed hypoglycemia (PG less than 56 mg/dL) were lower for IDegAsp and glargine than for the 55/45 version (1.2, 0.7, and 2.4 events per patient-year, respectively). One confirmed nocturnal hypoglycemic event was reported for IDegAsp in one patient and three events were reported in three patients on insulin glargine. No other adverse events were reported.

This study was funded by Novo Nordisk, which is now proceeding with phase III trials of insulin degludec.

Dr. Zinman's and Dr. Heise's institution receive research funding from manufacturers of diabetes-related products. Dr. Zinman has financial ties with GlaxoSmithKline, Merck, Amylin Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc., Eli Lilly and Co., and Medtronic Minimed. Dr. Heise serves on an advisory panel for Novo Nordisk.

At the trial's end, mean daily insulin doses were lower for the analogue than for glargine.

Source DR. HEISE

ORLANDO — A novel investigational ultra–long-acting insulin analogue produced glycemic control similar to insulin glargine when injected once daily or three times weekly, with better postdinner control.

The analogue, insulin degludec, forms soluble multihexamer depots after subcutaneous injection, resulting in a longer duration of action than any available insulin analogue. Novo Nordisk is developing two formulations, one of degludec alone and the other a 70/30 combination with the short-acting insulin aspart. There is no 70/30 formulation on the market that includes a basal insulin, Dr. Bernard Zinman said in an interview.

Data from two phase II proof-of-concept trials presented at the scientific sessions suggest that insulin degludec provides glucose control comparable to regimens using available basal insulins, with the advantages of fewer injections, better postdinner control, and possibly less hypoglycemia.

Dr. Zinman, professor of medicine and director of the Leadership Sinai Centre for Diabetes at the University of Toronto, reported on a 16-week, open-label, parallel-group, treat-to-target trial in which 245 patients with type 2 diabetes that was inadequately controlled by oral agents were randomized to one of four arms: the 70/30 formulation; a once-daily 55/45 formulation, which has since been discontinued; a three-times-weekly formulation (Monday, Wednesday, and Friday); or insulin glargine. All insulins were injected in the evening and titrated to target a fasting plasma glucose (FPG) of 72-108 mg/dL. All patients also continued taking metformin.

At baseline, the patients had a mean age of 54 years, mean hemoglobin A_1c of 8.7%, mean FPG of 184 mg/dL, and mean body mass index of 29.5 kg/m

After 16 weeks, reduction in HbA_1c from baseline was similar across treatment arms, with drops of 1.3 percentage points with once-daily insulin degludec, 1.5 points with thrice-weekly degludec, and 1.5 points with insulin glargine. Final mean HbA_1c also did not differ between groups, at 7.4% for once-daily degludec, 7.3% for the thrice-weekly version, and 7.2% for insulin glargine. Results for the 55/45 formulation were not reported.

FPG reductions were similar, as were final mean FPG (113, 116, and 115 mg/dL). Mean weekly insulin doses were similar at the end of the trial.

Rates of confirmed hypoglycemia(plasma glucose value of less than 56 mg/dL or requiring assistance) were low and only one severe event was reported (for thrice-weekly degludec). The rate of confirmed hypoglycemia was lower with once-daily degludec than with the thrice-weekly formulation and glargine, but the differences were not statistically significant (0.6, 2.3, 1.1 events per patient-year, respectively).

The proportion of subjects with adverse events did not differ significantly across treatment arms, with no specific patterns or clustering. Most adverse events were mild or moderate in severity, he said.

Dr. Tim Heise, CEO of the Profil Institute for Metabolic Research Ltd., Neuss, Germany, presented the data on the 70/30 degludec-aspart combination (IDegAsp). This 16-week open-label, parallel-group, treat-to-target trial randomized 178 patients who were inadequately controlled on oral agents to receive either once-daily 70/30 IDegAsp, the alternate 55/45 combination, or insulin glargine, all in combination with metformin. (Because the 55/45 combination has been discontinued, reports for that group are not available.)

Both insulins were dosed before dinner and titrated to an FPG target of 72-108 mg/dL. The patients had a mean age of 59 years, HbA_1c of 8.5%, and FPG of 209 mg/dL. After 16 weeks, mean HbA_1c decreased from baseline in both treatment groups, by 1.31 percentage points with IDegAsp and by 1.29 with insulin glargine. HbA_1c values were comparable: 7.0% for IDegAsp and 7.1% for insulin glargine. The proportions achieving HbA_1c values of less than 7.0% without confirmed hypoglycemia were 51% for IDegAsp and 50% with glargine, Dr. Heise reported.

The mean increase in plasma glucose at 2 hours after dinner was significantly lower for degludec than for glargine (2 mg/dL for IDegAsp versus 29 mg/dL with glargine), while FPG was similar between groups (122 and 126 mg/dL, respectively). At the trial's end, mean daily insulin doses were lower for IDegAsp than for insulin glargine.

No severe hypoglycemic events were reported. Rates of confirmed hypoglycemia (PG less than 56 mg/dL) were lower for IDegAsp and glargine than for the 55/45 version (1.2, 0.7, and 2.4 events per patient-year, respectively). One confirmed nocturnal hypoglycemic event was reported for IDegAsp in one patient and three events were reported in three patients on insulin glargine. No other adverse events were reported.

This study was funded by Novo Nordisk, which is now proceeding with phase III trials of insulin degludec.

Dr. Zinman's and Dr. Heise's institution receive research funding from manufacturers of diabetes-related products. Dr. Zinman has financial ties with GlaxoSmithKline, Merck, Amylin Pharmaceuticals Inc., Boehringer Ingelheim Pharmaceuticals Inc., Eli Lilly and Co., and Medtronic Minimed. Dr. Heise serves on an advisory panel for Novo Nordisk.

At the trial's end, mean daily insulin doses were lower for the analogue than for glargine.

Source DR. HEISE