No Evidence of Increased Physical Activity–Related Hypoglycemia with Once-Weekly Insulin Icodec vs. Once-Daily Basal Insulin in Type 2 Diabetes—ONWARDS 1–5

Introduction & Objective: The ONWARDS (ON) phase 3a trials showed the efficacy and safety of once-weekly (OW) basal insulin icodec (icodec) vs once-daily (OD) basal insulin comparators. This post hoc analysis examined physical activity (PA)-related hypoglycemia (measured by BG), based on self-reported data, in adults with T2D in ON 1-5.

Methods: Hypoglycemia occurrence was evaluated in insulin-naive (ON 1, 3, 5) and insulin-treated (ON 2, 4) adults with T2D receiving icodec vs OD comparators. In each trial, participants who experienced hypoglycemic episodes were instructed to note any relation to PA in a digital diary.

Results: The number of PA-related level 2 or level 3 hypoglycemic episodes was low in all trials, except ON 4 (basal-bolus trial). The proportion of hypoglycemic episodes that were related to PA trended higher or was comparable with icodec vs OD comparators in insulin-naive T2D and trended lower or was comparable in insulin-experienced T2D. There were no statistically significant differences in the odds of experiencing a PA-related level 2 or level 3 hypoglycemia for icodec vs OD comparators.

Conclusion: The incidence of PA-related level 2 or level 3 hypoglycemia in T2D was low in these trials of basal insulins and was not worsened by treatment with icodec vs OD basal insulin comparators. Despite some uncertainty due to low incidences, these data are reassuring.

Publication History

Article published online:
28 May 2025