CGM-derived postprandial glucose with IcoSema versus other insulin regimens: a post hoc analysis of COMBINE 1 and 3

SummaryBackground Impaired insulin and incretin responses, alongside elevated postprandial glucose (PPG) levels after meals, are hallmarks of type 2 diabetes (T2D) and can lead to postprandial hyperglycaemia. This post hoc analysis used PPG levels derived from continuous glucose monitoring (CGM) to investigate the effect of IcoSema versus other insulin-based regimens on PPG control in T2D. Methods In this post hoc analysis, a modified Glucose Rate Increase Detector (GRID) algorithm was used to assess the effect of IcoSema compared with once-weekly basal insulin icodec (icodec) or daily basal-bolus therapy (BBT) on PPG endpoints in adults with inadequately controlled T2D, using data from the COMBINE 1 and 3 trials. In the randomised, phase 3a COMBINE 1 and 3 trials, IcoSema (a once-weekly combination therapy of basal insulin icodec icodec and semaglutide) was investigated versus icodec (COMBINE 1) or daily BBT (insulin glargine U100 + insulin aspart; COMBINE 3). CGM data collected during weeks 48–52 were used to estimate mealtimes using the GRID algorithm and to derive PPG endpoints. The primary aim of this analysis was to use CGM data collected during the final 4 weeks of treatment in COMBINE 1 and 3 to determine the effect of IcoSema versus other insulin-based regimens on PPG control in individuals with T2D. Data were analysed using the full analysis set (all randomly assigned participants) and the on-treatment period. Participants were screened between June 1, 2022–March 13, 2023, in COMBINE 1 and November 30, 2021–September 28, 2022, in COMBINE 3. COMBINE 1 and 3 are registered on ClinicalTrials.gov (NCT05352815 and NCT05013229, respectively) and are complete. Findings Data from 1650 participants were analysed. In both trials, an average of 2.3 meals/day/participant were detected. IcoSema treatment resulted in statistically significantly lower mean peak PPG increment, 90-min PPG increment, and 120-min PPG increment values and a faster time to return to normal glucose levels versus once-weekly basal insulin (all p p = 0.0009); however, there were no statistically significant differences in mean peak PPG increment, 90-min PPG increment, or time to return to normal glucose levels. Interpretation IcoSema provided statistically significantly better PPG control than once-weekly icodec and similar PPG control versus daily BBT with only one weekly injection. Future studies that prospectively evaluate CGM-derived PPG outcomes and their clinical relevance across different meal compositions in real-world treatment settings would be beneficial. Funding Novo Nordisk A/S.