RCT | Weekly insulin Icodec proves effective in glucose control in insulin-naive type 2 diabetes patients

Summary: The ONWARDS 3 randomized clinical trial studied the efficacy of once-weekly insulin icodec in comparison to once-daily insulin degludec for glucose control in insulin-naive type 2 diabetes patients. The double-masked, double-dummy trial was conducted from March 2021 to June 2022 across 92 sites in 11 countries, enrolling 588 adults with type 2 diabetes. The participants were randomly divided into two groups: 294 receiving once-weekly icodec and daily placebo, and 294 receiving daily degludec and weekly placebo.

The primary endpoint was the change in Hemoglobin A1c (HbA1c) from baseline to week 26. Insulin icodec showed a noninferior HbA1c change from the baseline (-1.6 percentage points) compared to insulin degludec (-1.4 percentage points) and demonstrated confirmed statistical superiority. However, the trial showed a higher rate of combined level 2 (clinically significant) or level 3 (severe) hypoglycemic events in the insulin icodec group than in the insulin degludec group, despite the overall low rates in both groups. There was no significant difference in weight changes between the two groups.

The study concluded that once-weekly insulin icodec demonstrated superior HbA1c reduction compared to once-daily degludec after 26 weeks of treatment in insulin-naive type 2 diabetes patients. The convenience of once-weekly administration should be considered against the slightly higher absolute risk of hypoglycemia. The study’s limitations include its short duration (26 weeks) and a lack of data on sustained effects, patient-reported outcomes, and continuous glucose monitoring.

Article: Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial – JAMA (link to abstract – $ for full-text)

See also: Visual Abstract

Related Study: Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin – New England Journal of Medicine (link to abstract – $ for full-text)