QWINT-1: Weekly Insulin Efsitora Matches Daily Insulin in Type 2 Diabetes

For people with type 2 diabetes starting insulin therapy, a once-weekly insulin named efsitora alfa is just as effective in lowering blood glucose as a daily regimen with basal insulin, according to a new study.

Named the QWINT-1 trial, the study, which was presented at the 85th Scientific Sessions of the American Diabetes Association (ADA 2025) and simultaneously published in The New England Journal of Medicine, once-weekly efsitora alfa was associated with a reduction in HbA1c from 8.20% at baseline to 7.05% at week 52 compared to a reduction from 8.28% to 7.08% among the placebo group.1

“The results confirm once-weekly insulin efsitora can deliver similar level of blood sugar control as daily basal insulin, with the added benefit of a simpler dosing schedule,” said lead investigator Julio Rosenstock, MD, senior scientific advisor of Velocity Clinical Research at Medical City Dallas, and clinical professor of medicine at the University of Texas Southwestern Medical Center.2

Part of the QWINT clinical trial program, QWINT-1 was launched in 2023 to explore the safety and efficacy of a fixed-dose regimen of once-weekly efsitora alfa relative to daily basal insulin among patients with type 2 diabetes who are insulin-naive. The other trials in the program are also aimed at assessing once-weekly efsitora alfa for adults with diabetes. QWINT-2 evaluated insulin-naïve adults with type 2 diabetes, QWINT-3 studied those switching from daily basal insulin, QWINT-4 assessed patients intensifying from basal-bolus regimens, and QWINT-5 focused on adults with type 1 diabetes transitioning from daily basal insulin.1,3

A 52-week, phase 3, open-label, treat-to-target trial, QWINT-1 randomized 795 patients in a 1:1 ratio to receive once-weekly efsitora or once-daily insulin glargine U100. Per trial protocol, efsitora alfa was initiated as a single dose of 100 units administered once weekly, with dose adjustments made every 4 weeks, as needed, at fixed doses of 150, 250, and 400 unites to achieve fasting blood glucose levels of 80 to 130 mg/dL while doses of glargine were adjusted weekly or more often according to a standard algorithm to reach the same glycemic goals.1

For inclusion in the trial, patients needed to be adults with type 2 diabetes who had not previously received insulin, have an HbA1c of 7.0% to 10.0%, and have a BMI of 45.0 kg/m2 or less. Patients could still participate in the trial if they had received stable treatment with 1 to 3 noninsulin glucose-lowering agents for at least 3 months before screening. The overall study cohort had a mean age of 56.3 (SD, 9.8) years, 49.9% were female, 68.3% were White, 93.5% were using metformin, and had a mean duration of diabetes of 9.4 (SD, 6.7) years.1

The trial's primary outcome of interest was the change from baseline in HbA1c at 52 weeks, which was assessed for noninferiority with a noninferiority margin of 0.4 percentage points.1

Results of the study suggested the mean HbA1c level decreased from 8.20% at baseline to 7.05% at week 52 with efsitora alfa (least-squares mean change, -1.19 percentage points) and from 8.28% to 7.08% with daily basal insulin (least-squares mean change, -1.16 percentage points), which correlates to an estimated between-group difference of −0.03 percentage points (95% confidence interval [CI], -0.18 to 0.12). Investigators noted noninferiority was confirmed but superiority of the once-weekly approach was not shown (P = .68). Additionally, 52-week results demonstrating the mean total weekly insulin use was 289.1 units per week with efsitora alfa and 332.8 units per week with daily basal insulin (estimated between-group difference, -43.7 units per week; 95% CI, -62.4 to -25.0).1

Analysis of safety data from the trial suggested the rate of clinically significant hypoglycemia or severe hypoglycemia was lower with efsitora alfa than with daily basal insulin (0.50 vs 0.88 events per participant-year; estimated rate ratio, 0.57 [95% CI, 0.39 to 0.84]). Investigators also pointed out the median number of dose adjustments needed among participants was 2 with efsitora alfa and 8 with daily basal insulin.1

“The novel fixed-dose regimen used in QWINT-1 for once-weekly efsitora, with titration options of only four different doses, has the potential to facilitate and ease the burden of starting insulin for both patients and providers, hopefully, improving adherence and long-term health outcomes, is a significant step forward in filling a treatment gap that existed for decades," Rosenstock added.2

In a linked editorial, Julie R. Ingelfinger, MD, a professor of Pediatrics at Harvard Medical School, and Clifford J. Rosen, MD, director of Clinical and Translational Research and a senior scientist at Maine Medical Center's Research Institute, noted the importance of expanding patient choice within diabetes management, called attention to the limitations of trials assessing weekly insulins, and highlighted the dosing regimen used in the trial could serve as a guide if efsitora alfa were to receive regulatory approval.3

“The present trial of efsitora potentially offers a ready-made and possibly straightforward algorithm for dose escalation. If packaged at a widely affordable price, efsitora would most likely simplify glycemic control for many persons with type 2 diabetes. In all, weekly or, eventually, even more widely spaced insulin preparations may facilitate easier-to-administer insulin and dependable control of diabetes, thus lessening the barriers to the effective therapy of type 2 diabetes,” wrote the pair.3

References:

1. Rosenstock J, Bailey T, Connery L. Weekly Fixed-Dose Insulin Efsitora in Type 2 Diabetes without Previous Insulin Therapy. The New England Journal of Medicine. Published online June 22, 2025. doi: 10.1056/NEJMoa2502796

2. American Diabetes Association. Once-Weekly Insulin Efsitora Achieves Comparable A1C Reduction to Daily Insulin Therapy. PR Newswire. Published June 22, 2025. Accessed June 22, 2025. https://www.prnewswire.com/news-releases/once-weekly-insulin-efsitora-achieves-comparable-a1c-reduction-to-daily-insulin-therapy-302487408.html

3. Ingelfinger JR, Rosenson CJ. Weekly Insulins and Therapeutic Burden in Type 2 Diabetes. The New England Journal of Medicine. Published online June 22, 2025. doi: 10.1056/NEJMe2508147