Weekly insulin-semaglutide combination (IcoSema) provides greater blood sugar control than semaglutide alone | Research

The takeaway

The COMBINE 2 trial shows switching to weekly IcoSema (insulin icodec + semaglutide) from semaglutide alone provides greater HbA1c reduction with similar hypoglycemia risk, though with unfavorable weight change.

Greater HbA1c reduction
Weekly IcoSema combination outperformed semaglutide alone for blood sugar control with similar hypoglycemia risk

What the researchers found

IcoSema (weekly insulin icodec + semaglutide) achieved greater HbA1c reduction than semaglutide alone, with similar hypoglycemia risk and GI tolerability but unfavorable weight change, in T2DM patients inadequately controlled on GLP-1 RA therapy.

Why it matters

Many diabetes patients eventually need insulin despite GLP-1 therapy. A convenient once-weekly combination injection that improves glycemic control while maintaining the benefits of GLP-1 therapy simplifies treatment intensification and may improve adherence.

The numbers in context

COMBINE 2 trial data discussed; IcoSema showed greater HbA1c reduction vs semaglutide alone; similar hypoglycemia; unfavorable weight change with IcoSema.

How the study worked

Review of the COMBINE 2 randomized clinical trial comparing IcoSema to semaglutide in T2DM patients on GLP-1 RA therapy with or without oral glucose-lowering drugs.

Who was studied

Adults with type 2 diabetes inadequately controlled on GLP-1 RA therapy

What this study cannot tell us

Review focused on one trial. Weight trade-off may limit adoption. Long-term outcome data needed. Comparison was against semaglutide alone, not basal-bolus insulin.

How to read the evidence

Review of a randomized clinical trial (COMBINE 2). Strong evidence for efficacy comparison but limited to one trial.

When this study was published

Published in 2025; reviews the recently published COMBINE 2 trial.

The bigger picture

Fixed-ratio combinations of insulin and GLP-1 agonists represent a pragmatic approach to treatment intensification that avoids the complexity of basal-bolus insulin regimens. Weekly dosing (vs. daily for current combinations) could significantly improve patient convenience.

Questions still open

Can exercise and dietary modifications offset the weight disadvantage of IcoSema?
How does IcoSema compare to tirzepatide for intensification?
Will once-weekly convenience improve long-term adherence enough to offset weight concerns?

Common questions

What is IcoSema?

IcoSema is a once-weekly injection combining insulin icodec (a long-acting weekly insulin) with semaglutide (a GLP-1 agonist) in a single pen. It simplifies treatment for people with type 2 diabetes who need both insulin and GLP-1 therapy.

Why might someone switch from semaglutide to IcoSema?

If semaglutide alone is not adequately controlling blood sugar, adding insulin is the next step. IcoSema provides this intensification in a single weekly injection rather than requiring separate daily insulin shots, improving convenience while achieving better glucose control.

Read the original research

COMBINE 2 is better than one: shaping the future of therapeutics in inadequately controlled type 2 diabetes.

Expert review of clinical pharmacology, 18(5), 259-262

View on PubMed ↗Publisher’s paper ↗

Citation

Popovic, Djordje S; Patoulias, Dimitrios; Koufakis, Theocharis; Papanas, Nikolaos. (2025). COMBINE 2 is better than one: shaping the future of therapeutics in inadequately controlled type 2 diabetes.. Expert review of clinical pharmacology, 18(5), 259-262. https://doi.org/10.1080/17512433.2025.2516784