Continuous Glucose Monitoring–Based Metrics and Hypoglycemia Duration in Insulin-Experienced Individuals With Long-Standing Type 2 Diabetes Switched From a Daily Basal Insulin to Once-Weekly Insulin Icodec: Post Hoc Analysis of ONWARDS 2 and ONWARDS 4

What is it about?

Currently available basal insulin treatments for type 2 diabetes are injected once or twice daily. Insulin icodec (icodec) is a basal insulin analog in development which can be injected once weekly. The ONWARDS phase 3a clinical program, which comprised six clinical trials, aimed to test the efficacy and safety of icodec in various clinical scenarios. ONWARDS 2 and ONWARDS 4 are 26-week randomized clinical trials that investigated treatment with once-weekly icodec compared with once-daily basal insulins (ONWARDS 2: insulin degludec; ONWARDS 4: insulin glargine U100). Both trials included people with long-standing type 2 diabetes who had previously received insulin therapy; participants switched from daily basal insulin to trial basal insulin treatment either as a basal-only regimen (ONWARDS 2) or as part of a basal-bolus regimen (ONWARDS 4). Primary results from these clinical trials have been previously published and showed that treatment with icodec was associated with a statistically greater (ONWARDS 2) or comparable (ONWARDS 4) reduction in HbA1c compared to currently available once-daily basal insulins, with no statistically significant differences in the rates of clinically significant or severe hypoglycemia. This article presents a post hoc analysis in which continuous glucose monitoring (CGM) data from ONWARDS 2 and 4 were assessed. These CGM data provided a comprehensive, detailed picture of glycemic levels over time and the duration of hypoglycemic episodes. In both trials, CGM data were collected during three prespecified time periods: just after initiation of trial treatment, before the end of trial treatment and in the weeks following the end of trial treatment. In both trials, across all three CGM assessment periods, mean time spent with sensor glucose levels within the target range (TIR) and above the target range (TAR) was comparable for once-weekly icodec and comparator once-daily insulins; mean time spent with glucose levels below the target range (TBR) remained within internationally recommended targets. In addition, median duration of CGM-derived hypoglycemic episodes was comparable for icodec and once-daily insulin comparators across all CGM periods (all median durations ≤40 mins).

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Photo by Towfiqu barbhuiya on Unsplash

Photo by Towfiqu barbhuiya on Unsplash

Why is it important?

This post hoc CGM analysis provides a detailed evaluation of glycemic levels and hypoglycemia duration during three key time periods in ONWARDS 2 and 4, adding to the evidence to support the efficacy and safety of once-weekly icodec in insulin-experienced people with type 2 diabetes. Compared with currently available basal insulins, once-weekly insulin icodec could reduce the annual basal insulin injection burden from at least 365 injections to 52 injections among people with type 2 diabetes.