A Research Study to See How Well the New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Level in People With Type 2 Diabetes Compared to Insulin Glargine Taken Daily With Insulin Aspart (COMBINE 3)

Summary

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to insulin glargine taken daily with insulin aspart in people with type 2 diabetes.The study will look at how well IcoSema controls blood sugar level in people with type 2 diabetes compared to insulin glargine taken with insulin aspart. Participants will either get IcoSema or insulin glargine taken with insulin aspart. Which treatment participants get is decided by chance. IcoSema is a new medicine that doctors cannot prescribe. Doctors can already prescribe insulin glargine and insulin aspart in many countries. Participants will get IcoSema or insulin glargine together with insulin aspart. Participants must inject IcoSema once a week or inject insulin glargine once daily and insulin aspart 2-4 times a day. Participants will inject the medicines with a pen, which has a small needle, in a skin fold in the thigh, upper arm, or stomach. The study will last for about 1 year and 1 month. Participants will be asked to wear a sensor that measures participants blood sugar level all the time during an 8 week period at the beginning of the study and a 4 week period at the end of the study. Women cannot take part if pregnant, breast-feeding or plan to get pregnant during the study period.

Timeline

Start

2021-11-30

Primary completion

2023-11-14

Completion

2023-11-14

Publications

• De Block C, Benamar M, Fu A, Maltesen R, Giorgino F. CGM-derived postprandial glucose with IcoSema versus other insulin regimens: a post hoc analysis of COMBINE 1 and 3. EClinicalMedicine. 2026 Jun 4;96:103985. doi: 10.1016/j.eclinm.2026.103985. eCollection 2026 Jun.
• Billings LK, Andreozzi F, Frederiksen M, Gourdy P, Gowda A, Ji L, Pletsch-Borba L, Suzuki R, Unnikrishnan AG, Vianna AGD. Once-weekly IcoSema versus multiple daily insulin injections in type 2 diabetes management (COMBINE 3): an open-label, multicentre, treat-to-target, non-inferiority, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2025 Jul;13(7):556-567. doi: 10.1016/S2213-8587(25)00052-X. Epub 2025 Jun 4.

Drugs

Indications