BACKGROUND: In previous treat-to-target trials, adjustments to the dose of basal insulin have been made at least weekly, according to fasting blood glucose levels. A fixed-dose regimen of insulin efsitora alfa (efsitora), a once-weekly basal insulin, may provide a benefit in adults with type 2 diabetes who have not received previous insulin therapy.
METHODS: We conducted a 52-week, phase 3, open-label, treat-to-target trial involving adults with type 2 diabetes who had not previously received insulin therapy. Participants were randomly assigned in a 1:1 ratio to receive once-weekly efsitora or once-daily insulin glargine U100 (glargine). Treatment with efsitora was initiated as a single dose of 100 U administered once weekly, with dose adjustments made every 4 weeks, as needed, at fixed doses of 150, 250, and 400 U to achieve fasting blood glucose levels of 80 to 130 mg per deciliter. Doses of glargine were adjusted weekly or more often according to a standard algorithm to reach the same glycemic goals. The primary end point, tested for noninferiority (noninferiority margin, 0.4 percentage points), was the change from baseline in the glycated hemoglobin level at 52 weeks.
RESULTS: A total of 795 participants underwent randomization. The mean glycated hemoglobin level decreased from 8.20% at baseline to 7.05% at week 52 with efsitora (least-squares mean change, -1.19 percentage points) and from 8.28% to 7.08% with glargine (least-squares mean change, -1.16 percentage points); the estimated between-group difference of -0.03 percentage points (95% confidence interval [CI], -0.18 to 0.12) confirmed the noninferiority of efsitora to glargine. Superiority was not shown (P = 0.68). The rate of combined clinically significant hypoglycemia (glucose level, <54 mg per deciliter) or severe hypoglycemia (level 3; requiring assistance for treatment) was lower with efsitora than with glargine (0.50 events per participant-year of exposure with efsitora vs. 0.88 with glargine; estimated rate ratio, 0.57 [95% CI, 0.39 to 0.84]). At week 52, the mean total weekly insulin dose was 289.1 U per week with efsitora and 332.8 U per week with glargine (estimated between-group difference, -43.7 U per week; 95% CI, -62.4 to -25.0); the median number of dose adjustments needed was 2 with efsitora and 8 with glargine.
CONCLUSIONS: 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. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT05662332.).
