Once‑weekly IcoSema versus once‑weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial – published online 17/01/2025

Ildiko Lingvay, Malik Benamar, Liming Chen, Ariel Fu, Esteban Jódar, Tomoyuki Nishida, Jean‑Pierre Riveline, Daisuke Yabe, Thomas Zueger, Rosângela Réa

For many people living with type 2 diabetes, the progressive nature of the disease means that insulin therapy often becomes necessary once non-insulin glucose-lowering therapies can no longer maintain acceptable glycaemic control. IcoSema is a once-weekly combination therapy of basal insulin icodec and semaglutide designed to improve glycaemic control with reduced injection frequency. The COMBINE Phase IIIa programme has evaluated the efficacy and safety of IcoSema across three 52 week trials, in different populations of individuals with type 2 diabetes. In this issue, Lingvay et al (https://doi.org/10.1007/s00125-024-06348-5) present key findings of the COMBINE 2 trial, which compared IcoSema with semaglutide 1.0 mg. The authors report that IcoSema shows superior reduction in HbA_1c and greater improvement in fasting plasma glucose, alongside comparable rates of clinically significant or severe hypoglycaemia. However, weight change favoured use of semaglutide 1.0 mg alone. The authors conclude that these results suggest that IcoSema offers a simple and effective solution for managing type 2 diabetes inadequately controlled with glucagon-like peptide-1 receptor agonists.