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

Abstract

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 <i>post hoc</i> 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. In this <i>post hoc</i> 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. 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 <i>p</i> < 0.0001). The 120-min PPG increment was also statistically significantly lower with IcoSema versus daily BBT (<i>p</i> = 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. 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. Novo Nordisk A/S.