Once-Weekly Insulin Icodec: Safety Profile in Type 2 and Type 1 Diabetes Based on a Pooled Analysis of ONWARDS 1-6

To describe the safety profile of once-weekly insulin icodec (icodec), focusing on aspects beyond hypoglycemia, in a pooled population from the ONWARDS phase 3a trials.

ONWARDS 1-6 investigated the efficacy and safety of icodec versus once-daily basal insulin comparators in insulin-naive and insulin-experienced adults with type 2 diabetes, and insulin-experienced adults with type 1 diabetes. Adverse event (AE) data from all trial periods were pooled. Hypersensitivity, injection-site reactions, and medication errors, as well as microvascular and macrovascular (including time to first major adverse cardiovascular event [MACE]) complications, were among the safety areas evaluated.

Total treatment exposure was 2118.70 and 2127.76 patient-years of exposure (PYE) in the icodec (n = 2170) and comparator groups (n = 2170), respectively. Adjusted rates (events/100 PYE) were similar for icodec and comparators for all AEs (248.49 vs 242.53), serious AEs (14.51 vs 14.03), and severe AEs (7.92 vs 7.50), respectively. Adjusted rates of hypersensitivity were 5.88 and 6.74 events/100 PYE in the icodec and comparator groups, respectively. Most injection-site reactions were mild; adjusted rates: 5.86 and 3.66 events/100 PYE, respectively. Medication error rates were 2.47 and 2.53 events/100 PYE, respectively. Time to first MACE was similar between groups (hazard ratio [95% confidence interval]: 0.93 [0.56-1.56]). Adjusted rates for other AEs were broadly similar between groups.

Based on a detailed evaluation of safety focus areas across the ONWARDS 1-6 trials, the safety profile of once-weekly icodec was generally similar to that of once-daily basal insulin comparators in individuals with type 2 diabetes or type 1 diabetes.