238-OR: Once-Weekly Basal Insulin Icodec Offers Comparable Efficacy and Safety vs. Once-Daily Insulin Glargine U100 in Insulin-Naïve Patients with T2D Inadequately Controlled on OADS

Abstract

Insulin icodec^* (icodec) is a novel basal insulin analog with a terminal half-life of ∼196 hours in development as the first once-weekly insulin. This 26-week, randomized, double-blind, double-dummy, treat-to-target, phase 2 trial investigated the efficacy and safety of once-weekly icodec vs. once-daily insulin glargine U100 (IGlar U100) in insulin-naïve patients with T2D inadequately controlled (A1C 7.0-9.5%) with metformin ± DPP-4i. Starting doses were 70 U weekly and 10 U daily, respectively, with weekly titration to a pre-breakfast SMBG target of 70-108 mg/dL. Primary endpoint was change in A1C from baseline to week 26. Secondary endpoints included change in FPG from baseline to week 26 and hypoglycemic episodes. Participants (n = 247) were randomized 1:1 to icodec (n = 125) or IGlar U100 (n = 122). Baseline characteristics appeared similar in both groups; mean age was 59.6 years, diabetes duration 9.7 years, BMI 31.3 kg/m² and FPG 181 mg/dL. Mean baseline A1C was 8.1% (icodec) and 8.0% (IGlar U100). At week 26, estimated mean A1C was 6.69% for icodec and 6.87% for IGlar U100 (estimated mean change from baseline: -1.33% and -1.15%-points, respectively). There was no statistically significant treatment difference for change in A1C from baseline to week 26 (-0.18%, 95% CI, -0.38; 0.02). Estimated mean FPG at week 26 was 123 mg/dL (icodec) and 127 mg/dL (IGlar U100). Observed rates of level 2 (<54 mg/dL) + 3 (severe) hypoglycemia were low (60.55 and 52.36 events per 100 patient years of exposure for icodec and IGlar U100, respectively) and were comparable (p = 0.85). There were no unexpected safety findings.

In conclusion, icodec is the first once-weekly insulin with similar glucose-lowering effects and safety profile to once-daily IGlar U100. Icodec could improve treatment acceptance and facilitate T2D management in patients needing basal insulin. ^*Proposed INN.