Once-weekly basal insulin noninferior to once-daily insulin for type 1, type 2 diabetes
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Key takeaways:
- Change in HbA1c and hypoglycemia rates were similar between once-weekly basal insulin and once-daily insulin degludec in phase 2 trials.
- Insulin efsitora alfa is being assessed in five ongoing phase 3 studies.
A once-weekly basal insulin conferred similar changes in HbA1c and time in range as once-daily insulin glargine among adults with type 1 and type 2 diabetes in three phase 2 trials, according to a speaker.
Insulin efsitora alfa (Eli Lilly) is a once-weekly basal insulin that is currently being investigated in five different patient populations with diabetes in phase 3 trials. In phase 2 trials, insulin efsitora alfa was noninferior to once-daily insulin degludec among adults with type 2 diabetes who previously used basal insulin, those with type 2 diabetes who were insulin naive, and adults with type 1 diabetes. The results, along with findings from the ONWARDS clinical trials of once-weekly insulin icodec (Novo Nordisk), make once-weekly insulins a potential option for people with type 1 and type 2 diabetes in the future, according to Juan Pablo Frias, MD, chief medical officer of Biomea Fusion.
“From my perspective ... [once-weekly insulin] is almost a no-brainer with respect to type 2 diabetes,” Frias said during a presentation at the International Conference on Advanced Technologies & Treatments for Diabetes. “But having [treated] a lot of type 1 diabetes at the Barbara Davis Center, I do think it will have a role in some patients with type 1 diabetes, based on the ease of use and increased compliance in some patients.”
Phase 2 trial results
Results from three phase 2 studies on once-weekly basal insulin were published in 2023. In a study published in The Lancet Diabetes & Endocrinology, people with type 2 diabetes who were previously receiving basal insulin were randomly assigned, 1:1:1, to one of two once-weekly basal insulin groups with different dosing algorithms or once-daily insulin degludec for 32 weeks. Target fasting glucose was 140 mg/dL for the first once-weekly basal insulin group, 120 mg/dL for the second once-weekly insulin group and 100 mg/dL for adults receiving insulin degludec. Unmasked continuous glucose monitoring was used by all participants.
At 32 weeks, adults receiving once-weekly basal insulin had a similar decline in HbA1c as those receiving insulin degludec. HbA1c change was similar despite participants in both once-weekly insulin groups having a higher fasting blood glucose compared with insulin degludec for nearly all of the study. Frias attributed the higher fasting glucose with once-weekly insulin to the higher target glucose values for those two groups.
Within-day glucose variability as measured by coefficient of variation was lower with once-weekly insulin compared with insulin degludec. Both once-weekly insulin groups had a lower rate of hypoglycemia than adults receiving insulin degludec.
The second phase 2 study, published in Diabetes Care, compared once-weekly basal insulin with once-daily insulin degludec among insulin-naive adults with type 2 diabetes. Adults in both groups were treated with a target fasting glucose of 100 mg/dL and wore a masked CGM for 26 weeks.
The once-weekly insulin group had a similar reduction in HbA1c at 26 weeks as the insulin degludec group. The percentage of adults who achieved an HbA1c of less than 7% was 62.3% in the once-weekly insulin group and 68.6% with insulin degludec.
The two groups had similar reductions in fasting glucose from baseline to week 26. The once-weekly insulin group had a time in range of 76% at 26 weeks, similar to the 77.4% time in range for adults receiving insulin degludec. Rates of hypoglycemia were similar between the two groups and no severe hypoglycemia was reported in the study.
Another phase 2 trial was conducted among adults with type 1 diabetes. Participants were randomly assigned to once-weekly basal insulin or once-daily insulin degludec for 26 weeks. All participants continued prandial insulin therapy during the study. Target fasting glucose was less than 100 mg/dL and adults wore an unmasked CGM for the duration of the study.
Once-weekly basal insulin met the study’s predefined noninferiority margin for HbA1c at 26 weeks. The once-weekly insulin group had a 7.5% HbA1c at 26 weeks compared with a 7.33% HbA1c for the insulin degludec group. Frias noted the change in HbA1c among both groups was minimal during the study. At 26 weeks, the once-weekly insulin group had a 14.4 mg/dL higher fasting plasma glucose than the insulin degludec group.
“There was quite a rise in fasting glucose initially [with once-weekly insulin],” Frias said. “When you look at the paper, there probably was a 30% deficiency in the insulin and that the dosing algorithms were probably too conservative.”
Changes for time in range were similar between the two groups, with both groups having reductions in time in range at 26 weeks from baseline. No difference in hypoglycemia rates was observed between once-weekly insulin and insulin degludec. There were three cases of severe hypoglycemia, with one occurring in the once-weekly insulin group and two in the insulin degludec group.
Phase 3 trials nearing completion
Insulin efsitora alfa is now being assessed in five phase 3 trials that are part of the QWINT program. The QWINT-1 study enrolled insulin-naive participants with type 2 diabetes and randomly assigned them to once-weekly basal insulin or insulin glargine for 52 weeks. The QWINT-2 trial also enrolled insulin-naive adults with type 2 diabetes and randomly assigned them to once-weekly basal insulin or insulin degludec for 52 weeks. The QWINT-3 trial includes adults with type 2 diabetes who previously received basal insulin and were switched to once-weekly basal insulin or insulin degludec for 78 weeks. The QWINT-4 trial enrolled adults with type 2 diabetes receiving multiple daily injections and randomly assigned them to once-weekly basal insulin or insulin glargine for 52 weeks. The QWINT-5 trial included adults with type 1 diabetes and compared once-weekly basal insulin with insulin degludec.
Key endpoints in all of the trials include change in HbA1c, time in range and hypoglycemia from baseline to the end of the study. All five trials are scheduled to be completed by July.
References:
- Bue-Valleskey JM, et al. Diabetes Care. 2023;doi:10.2337/dc22-2396.
- Frias J, et al. Lancet Diabetes Endocrinol. 2023;doi:10.1016/S2213-8587(22)00388-6.
- Kazda CM, et al. Diabetes Care. 2023;doi:10.2337/dc22-2395.
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Frias JP. Update on weekly insulin efsitora alfa. Presented at: International Conference on Advanced Technologies & Treatments for Diabetes; March 6-9, 2024; Florence, Italy (hybrid meeting).
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