Research Summary

Efficacy, Safety of Once-Weekly Efsitora in Adults with Type 2 Diabetes Without Prior Insulin Use

Anthony Calabro, MA

Key Highlights

  • Once-weekly fixed-dose insulin efsitora was noninferior to once-daily insulin glargine for glycated hemoglobin (HbA1c) reduction at 52 weeks.
  • Lower rates of clinically significant or severe hypoglycemia occurred with efsitora compared with glargine.
  • Participants on efsitora required fewer dose adjustments (median 2 vs 8 with glargine).
  • Most patients (76%) remained on fixed dosing of efsitora, avoiding transition to variable dosing.

In a phase 3, randomized trial, once-weekly insulin efsitora demonstrated noninferiority to once-daily insulin glargine for type 2 diabetes without prior insulin use. At 52 weeks, reductions in HbA1c were comparable between groups, while efsitora was associated with fewer hypoglycemia events and required fewer dose adjustments, potentially simplifying initiation and management of glycemic control.

Daily basal insulin regimens can be burdensome and contribute to therapeutic inactivity, delaying timely intensification of therapy and leading to suboptimal glycemic control. Once-weekly insulin with a straightforward dosing strategy may reduce treatment complexity and injection burden, paralleling the established acceptance of weekly incretin-based therapies.

The QWINT-1 trial was an open-label, multinational, 52-week study enrolling 795 participants at 71 sites in Argentina, Mexico, and the United States. Eligible adults with type 2 diabetes had HbA1c levels of 7.0% to 10.0% and were on stable noninsulin glucose-lowering therapy. Participants were randomized to once-weekly efsitora or once-daily glargine. Efsitora was initiated at 100 U weekly, with fixed-dose escalations (150, 250, or 400 U) permitted every 4 weeks based on fasting glucose targets. Glargine doses were adjusted weekly using a standard algorithm. The primary endpoint was change in HbA1c from baseline to week 52, tested for noninferiority (margin 0.4%).

Both groups achieved significant reductions in HbA1c: from 8.20% to 7.05% with efsitora (least-squares mean change, −1.19 percentage points) and from 8.28% to 7.08% with glargine (−1.16 percentage points). The between-group difference (−0.03 percentage points; 95% CI, −0.18 to 0.12) confirmed noninferiority. Estimated percentages of participants reaching HbA1c <7.0% were 57% with efsitora and 52% with glargine. Fasting glucose reductions were similar. Importantly, efsitora required fewer dose adjustments (median 2 vs 8) and achieved target control with a lower total weekly insulin dose (289.1 U vs 332.8 U; difference, −43.7 U per week; 95% CI, −62.4 to −25.0).

Safety outcomes favored efsitora, with a 43% lower rate of combined clinically significant or severe hypoglycemia compared with glargine (0.50 vs. 0.88 events per participant-year; rate ratio, 0.57; 95% CI, 0.39 to 0.84). One severe hypoglycemia event occurred in each group. Weight gain was modest but slightly higher with efsitora (3.9 kg vs 3.3 kg). Overall adverse event rates and serious adverse events were similar between groups.

The study’s limitations include its open-label design, which may introduce bias, and the prohibition of reescalation of efsitora dose after reduction for hypoglycemia, which does not mirror routine practice. Continuous glucose monitoring was not performed, limiting hypoglycemia assessment.

"In adults with type 2 diabetes who had not previously received insulin, once-weekly efsitora, administered in a fixed-dose regimen, was noninferior to once-daily glargine in reducing glycated hemoglobin levels," the investigators concluded.

 

Reference
Rosenstock J, Bailey T, Connery L, et al; for the QWINT-1 trial investigators. Weekly fixed-dose insulin efsitora in type 2 diabetes without previous insulin therapy. N Engl J Med. 2025;393(4):325-335. doi:10.1056/NEJMoa2502796