European Association for the Study of Diabetes

European Association for the Study of Diabetes

Source:

Frias JP. OP-23. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 27-Oct. 1, 2021 (virtual meeting).

Disclosures: Eli Lilly sponsored this study. Frias reports he receives research support from Allergan, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Intercept, Janssen, Madrigal, Metacrine, Merck, NorthSea Therapeutics, Novartis, Novo Nordisk, Oramed, Pfizer, Poxil, Sanofi and Theracos; serves on advisory boards or is a consultant for 89bio, Altimmune, Axcella Health, Boehringer Ingelheim, Coherus Therapeutics, Echosens, Eli Lilly, Gilead, Intercept, Merck, Novo Nordisk and Sanofi; and is on the speakers bureau for Merck and Sanofi.
October 12, 2021
3 min read
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Novel once-weekly basal insulin safe, effective in type 2 diabetes

Source:

Frias JP. OP-23. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 27-Oct. 1, 2021 (virtual meeting).

Disclosures: Eli Lilly sponsored this study. Frias reports he receives research support from Allergan, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Intercept, Janssen, Madrigal, Metacrine, Merck, NorthSea Therapeutics, Novartis, Novo Nordisk, Oramed, Pfizer, Poxil, Sanofi and Theracos; serves on advisory boards or is a consultant for 89bio, Altimmune, Axcella Health, Boehringer Ingelheim, Coherus Therapeutics, Echosens, Eli Lilly, Gilead, Intercept, Merck, Novo Nordisk and Sanofi; and is on the speakers bureau for Merck and Sanofi.
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A novel once-weekly formulation of basal insulin was safe and effective in adults with long-standing type 2 diabetes, with lower rates of documented and nocturnal hypoglycemia over 32 weeks compared with insulin degludec, phase 2 data show.

Once-weekly basal insulin is anticipated to be the next important advancement in insulin therapy because it demonstrates several important advantages over daily insulin formulations, Juan Pablo Frias, MD, FACE, medical director and a principal investigator of the National Research Institute in Los Angeles, said during a presentation at the European Association for the Study of Diabetes annual meeting. A once-weekly therapy may lead to earlier adoption of insulin, improve adherence and lead to better real-world patient outcomes, Frias said.

Frias is medical director and a principal investigator of the National Research Institute in Los Angeles

“Additionally, a once-weekly insulin with a flat peak to trough profile throughout the week should reduce within-day glucose variability, resulting in more consistent and predictable glycemic control, potentially lowering risk for hypoglycemia,” Frias said.

Safety data

Frias and colleagues analyzed data from 399 adults with long-standing type 2 diabetes already treated with basal insulin and up to three oral diabetes medications. The mean age of participants was 60 years, mean baseline HbA1c was 8.1% and mean diabetes duration was 14.7 years.

Researchers randomly assigned participants in a 1:1:1 ratio to one of three parallel treatment groups: insulin degludec (Tresiba, Novo Nordisk) or once-weekly basal insulin (Eli Lilly) using one of two different dosing algorithms for 32 weeks, followed by a 6-week safety follow-up period. For safety reasons, target fasting glucose levels for the two once-weekly insulin arms were 140 mg/dL and 120 mg/dL, respectively, whereas insulin degludec was titrated to a fasting glucose target of 100 mg/dL, Frias said.

“With both formulations, insulin dose adjustments were made based on fasting glucose and [weekly insulin] adjustments were made in milligram rather than unit increments,” Frias said.

Primary endpoint was change in HbA1c from baseline to week 32; key secondary endpoints were fasting glucose change from baseline to week 32, incidence and rate of hypoglycemia and treatment-emergent severe adverse events.

Researchers found all three groups showed significant improvement in HbA1c from baseline to 32 weeks (P < .001) and change in HbA1c was noninferior between the two once-weekly insulin arms and insulin degludec (noninferiority margin = 0.4%). Mean HbA1c change from baseline was 0.6%, 0.6% and 0.7%, respectively, among the two once-weekly insulin arms and the insulin degludec arm. Fasting glucose, as expected, was higher with once-weekly insulin vs. insulin degludec throughout most of the trial due to higher fasting glucose targets.

Less hypoglycemia observed

A similar proportion of patients achieved an HbA1c of 7% without nocturnal hypoglycemia across the three study arms, Frias said.

Treatment with both once-weekly insulin titration algorithms resulted in a lower rate of overall documented hypoglycemia and lower nocturnal hypoglycemia. The correlation between the rate of hypoglycemia and fasting glucose was weak for both insulins, Frias said. For any given fasting glucose, the rate of severe hypoglycemia (< 54 mg/dL) was lower with once-weekly insulin vs. insulin degludec.

“It is important to point out that this analysis has limitations, including the fact that the study was not powered for treatment difference in hypoglycemia and extreme values for hypoglycemia rates were excluded from this analysis,” Frias said.

Incidence of overall and serious adverse events were comparable across groups. There were two incidents of severe hypoglycemia, both observed in once-weekly insulin patients; both were treated with oral carbohydrates by a third party, Frias said.

“[Once-weekly insulin] achieved similar glycemic control with respect to HbA1c after 32 weeks of treatment compared to insulin degludec, despite higher fasting glucose targets in patients with type 2 diabetes previously treated with basal insulin,” Frias said. “Treatment with [once-weekly insulin] resulted in lower rates of documented hypoglycemia and importantly lower rates of nocturnal hypoglycemia. Otherwise, [once-weekly insulin] demonstrated a similar overall safety profile compared with insulin degludec.”

A large phase 2 program exploring the efficacy and safety of once-weekly insulin in a broad patient population, including those with type 1 diabetes, compared with insulin degludec, is underway, with a fasting glucose target of 100 mg/dL, Frias said.