Eli Lilly has announced positive phase 3 top-line results for its once-weekly insulin efsitora alfa (efsitora) in insulin-naive adults with type 2 diabetes and those who require multiple daily insulin injections.
The new data come from the company’s QWINT-2 and QWINT-4 phase 3 clinical trials. In both, efsitora was noninferior to daily basal insulin in lowering A1c. The comparator was once-daily degludec in QUINT-2 and glargine in QUINT-4.
These results come days before the once-weekly competitor, Novo Nordisk’s insulin icodec, will be discussed by the US Food and Drug Administration’s Endocrinologic and Metabolic Drugs Advisory Committee. On May 24, 2024, the panel will review safety and efficacy of icodec for the proposed indication of improving glycemic control in adults with diabetes.
Hypoglycemia and Affordability Are Concerns
Asked to comment, Anne L. Peters, MD, director of the University of Southern California Westside Center for Diabetes, Los Angeles, told this news organization that she’s “cautiously optimistic” about once-weekly insulin. “I honestly think it’s going to have an important role in diabetes. … And I’m looking forward to learning how it’s going to help my patients.”
However, Dr. Peters also said she’s concerned about the possible risk for hypoglycemia with long-acting insulin, particularly in patients with variable schedules. “The real fear they have and I have is hypoglycemia. That being said, I think that it will be great for some patients where hypoglycemia is less of a concern, and they’re in a more stable environment. … I think there are patients who will really benefit but I have to figure out who those patients are.”
Dr. Peters, who takes care of many low-income patients, also pointed out that once approved, these newer insulins may not be affordable for those who could most benefit from them in terms of improved adherence. Insurance plans may not cover them initially, especially given that the data thus far show noninferiority, not superiority, to daily basal. “The patients in whom I would like to use it most are the patients who have the most trouble with social determinants of health and other issues. I really think it could really make a difference for them, but it won’t get there for a while.”
And, she noted, titrating doses of once-weekly insulin will likely come with a learning curve. “Having spent a lifetime adjusting basal insulin on a daily basis to suddenly do it on a weekly basis, as a diabetologist I’m going to have to get used to what that feels like.”
Topline Data Show Noninferiority to Daily Basal Insulin
In QWINT-2, efficacy and safety of once-weekly efsitora was compared with those of once-daily insulin degludec for 52 weeks. Study participants were all new to using insulin, but some were using glucagon-like peptide 1 receptor agonists.
The treat-to-target trial met its primary noninferiority endpoint for hemoglobin A1c reduction at week 52. A1c values were lowered by 1.34 percentage points with efsitora compared with 1.26 for insulin degludec, resulting in non–significantly different A1c values of 6.87% and 6.95%, respectively.
In QWINT-4, efficacy and safety of once-weekly efsitora was compared with those of daily insulin glargine for 26 weeks in adults with type 2 diabetes who had previously been treated with basal insulin and at least two injections of premeal insulin per day. Participants were randomized to receive efsitora once weekly or insulin glargine once daily, and both groups used lispro before meals.
This trial also met its primary endpoint, with both reducing A1c by 1.07 percentage points at 26 weeks, resulting in levels of 7.12% and 7.11%, respectively.
The full results for QWINT-2 will be presented at the European Association for the Study of Diabetes meeting this September.
Dr. Peters served on the advisory board for Abbott Diabetes Care; Becton Dickinson; Boehringer Ingelheim Pharmaceuticals, Inc.; Eli Lilly and Company; Lexicon Pharmaceuticals, Inc.; Livongo; Medscape Medical News; Merck & Co., Inc.; Novo Nordisk; Omada Health; OptumHealth; Sanofi; and Zafgen. She received research support from Dexcom, MannKind Corporation, and Astra Zeneca and served as a member of a speakers bureau for Novo Nordisk.
A version of this article first appeared on Medscape.com.