A Research Study to See How Well New Weekly Medicine IcoSema, Which is a Combination of Insulin Icodec and Semaglutide, Controls Blood Sugar Levels in People With Type 2 Diabetes (T2D), Compared to Daily Insulin Glargine (COMBINE 4)

What Was Tested

This registered phase 3 trial tested Insulin Glargine.

This study will compare the new medicine IcoSema, which is a combination of insulin icodec and semaglutide, taken once a week, to insulin glargine (mentioned as insulin glargine in this form) taken daily in people with type 2 diabetes.

The study will look at how well IcoSema controls blood sugar levels as compared to insulin glargine in people with type 2 diabetes who do not have their blood sugar properly controlled with other oral diabetes medicines.

Participant will either get IcoSema or insulin glargine.

It had two arms (groups): IcoSema (experimental) and Insulin glargine (experimental).

Participants will receive once weekly IcoSema subcutaneously with or without oral anti diabetic drugs for 40 weeks.

Participants will receive once daily insulin glargine subcutaneously with or without oral anti diabetic drugs for 40 weeks.

The registry classes the interventions as drug.

Who Took Part

485 actual participants took part.

It was open to people of any sex aged from 18 years with no upper age limit.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Male or female and age above or equal to 18 years at the time of signing the informed consent. Diagnosed with T2D greater than or equal to (≥) 180 days before screening. Insulin naïve. Short term insulin treatment for a maximum of 14 consecutive days before screening is allowed, as is prior insulin treatment for gestational diabetes. Dipeptidyl peptidase (DPP) 4 inhibitors. Sodium glucose co transporter 2 inhibitors.

The full record lists 14 inclusion and 8 exclusion criteria; among the exclusions: presence or history of pancreatitis (acute or chronic) within 180 days before screening; any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within 180 days before screening; chronic heart failure classified as being in new york heart association class iv at screening.

How the Study Was Run

It was run as a randomized, parallel-group and open-label study.

Because people in this Insulin Glargine study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

The Insulin Glargine group and the comparison group ran side by side rather than switching.

Everyone knew when Insulin Glargine was being given (open label), which is simpler to run but leaves more room for expectations to affect what is reported.

It started in 2024-02-15 with completion listed for 2025-05-27.

It ran at 118 sites in United States (43), India (16), Poland (14), China (9), Italy (8) and Turkey (Türkiye) (8).

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): Change in glycated haemoglobin (HbA1c) (time frame: From baseline (week 0) to week 40).

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of Insulin Glargine in 485 people.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Insulin Glargine compound page, all human trials.