Once-weekly IcoSema versus once-weekly semaglutide in adults with type 2 diabetes: the COMBINE 2 randomised clinical trial.
Summary
In this 52-week, multicenter, open-label Phase IIIa RCT (n=683), once-weekly IcoSema (icodec insulin + semaglutide) achieved superior HbA1c reduction versus once-weekly semaglutide 1.0 mg in adults with type 2 diabetes inadequately controlled on GLP-1 RAs. The study supports a simplified, once-weekly combination approach for intensification.
Key Findings
- 52-week, multicenter, Phase IIIa RCT across 121 sites randomized 683 adults to IcoSema (n=342) vs semaglutide 1.0 mg (n=341).
- Once-weekly IcoSema demonstrated superiority over semaglutide 1.0 mg in HbA1c reduction.
- Trial population comprised individuals inadequately managed on GLP-1 RAs, with or without additional oral agents.
Clinical Implications
For adults with T2D inadequately controlled on GLP-1 RAs, switching to once-weekly IcoSema can improve HbA1c with a simplified dosing schedule. Shared decision-making should consider open-label design, hypoglycemia risk, and weight effects pending full data.
Why It Matters
Demonstrates clinical superiority of a once-weekly fixed insulin–GLP-1 combination versus GLP-1 monotherapy in a large, global Phase III program, informing next-step intensification for patients not meeting glycemic targets on GLP-1 RAs.
Limitations
- Open-label design may introduce performance and detection bias.
- Abstract truncation precludes full visibility on weight change, hypoglycemia rates, and other secondary endpoints.
Future Directions
Report complete efficacy (including weight, TIR) and safety (hypoglycemia) outcomes; assess durability, cardiovascular/renal outcomes, and patient-reported outcomes; compare against basal–bolus or basal-plus regimens.
Study Information
- Study Type
- RCT
- Research Domain
- Treatment
- Evidence Level
- I - Randomized controlled trial with active comparator and 52-week follow-up
- Study Design
- OTHER