Once‑weekly IcoSema versus once‑weekly insulin icodec in type 2 diabetes management (COMBINE 1): an open‑label, multicentre, treat‑to‑target, randomised, phase 3a trial.

Summary

In a 52‑week, open‑label, treat‑to‑target, phase 3a RCT across 20 countries (n=1291), once‑weekly IcoSema (icodec+semaglutide) achieved superior HbA1c reduction versus once‑weekly icodec alone in adults with type 2 diabetes inadequately controlled on daily basal insulin. The trial supports efficacy of a simplified once‑weekly fixed‑ratio regimen.

Key Findings

• 52‑week, open‑label, treat‑to‑target, phase 3a RCT across 192 sites in 20 countries.
• 1291 participants randomized: IcoSema (n=646) vs icodec (n=645).
• IcoSema showed superiority to icodec alone in HbA1c change at week 52.

Clinical Implications

For adults inadequately controlled on daily basal insulin, once‑weekly IcoSema may provide greater glycaemic improvement with a simplified regimen, supporting consideration of fixed‑ratio insulin–GLP‑1RA co‑formulations in treatment pathways.

Limitations

• Open‑label design may introduce performance and detection bias.
• Industry funding; longer‑term durability and hard outcomes beyond 52 weeks not reported in the abstract.

Future Directions

Assess long‑term durability, cardiovascular and renal outcomes, hypoglycaemia and weight effects, and real‑world adherence/cost‑effectiveness of once‑weekly fixed‑ratio therapy.