Insights on hospitalisations from the phase 3a COMBINE 1–3 trials of once-weekly IcoSema in individuals with type 2 diabetes: a post hoc analysis

Abstract Aims/hypothesis The COMBINE phase 3a trials evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a glucagon-like peptide-1 [GLP-1] analogue) in adults with type 2 diabetes. This post hoc analysis of the COMBINE 1–3 trials evaluated the impact of IcoSema during and around hospitalisation. Methods Across the COMBINE 1–3 trials, 2637 adults with type 2 diabetes received IcoSema or a comparator (insulin icodec; semaglutide 1.0 mg; or insulin glargine U100 + insulin aspart). Hospitalisation data were recorded through adverse event reports as part of safety monitoring. Upon trial completion, available data were used to assess: overall number and duration of hospitalisations; treatment discontinuation; IcoSema dose; HbA 1c levels; self-measured blood glucose levels; and number of hypoglycaemia episodes before, during and after hospitalisation. Results Across trials, 106/1325 participants receiving IcoSema and 92/1312 participants receiving a comparator were hospitalised. Median duration of hospital stay was 4.0 days with IcoSema and 5.0 days with comparators. Most hospitalised participants completed their trial without permanently discontinuing treatment (IcoSema 96.2%; comparators 93.5%). Mean IcoSema dose remained fairly stable before and after hospitalisation. Numerical reductions in mean HbA 1c levels and generally stable self-measured blood glucose values were observed during and around hospitalisation in both treatment groups. Three participants receiving IcoSema and eight participants receiving a comparator reported clinically significant or severe hypoglycaemia during hospitalisation. Conclusions/interpretation Post hoc findings suggest that IcoSema did not affect hospitalisation incidence or duration, and IcoSema dosing remained stable before and after hospitalisation. Hospitalisation did not have a negative impact on glycaemic control, and the number of hypoglycaemia episodes with IcoSema was low during hospitalisation. Trial registration COMBINE 1: ClinicalTrials.gov, NCT05352815 (registered 24 April 2022); COMBINE 2: ClinicalTrials.gov, NCT05259033 (registered 10 February 2022); COMBINE 3: ClinicalTrials.gov, NCT05013229 (registered 13 August 2021).