REIMAGINE 3 tests CagriSema with basal insulin in type 2 diabetes

What happened

REIMAGINE 3 enrolled adults who still had above-target blood sugar while taking daily basal insulin for type 2 diabetes, either by itself or with metformin. The weekly CagriSema injection pairs the amylin receptor agonist cagrilintide with semaglutide, a GLP-1 receptor agonist.

The phase 3 trial enrolled 274 people at 46 centers in six countries. Participants had an A1C from 7.0% through 10.5% while using a stable basal-insulin regimen. They were randomly assigned to CagriSema containing 2.4 mg of each component, CagriSema containing 1.0 mg of each component or a dose-matched placebo for 40 weeks.

Average A1C at enrollment was 8.8%. Forty weeks later, it had dropped by an estimated 2.33 percentage points in the 2.4 mg combination arm and 2.10 points in the 1.0 mg arm. Placebo produced a 0.66-point decline. The corresponding advantages over placebo were 1.68 and 1.44 points. Depending on the CagriSema dose, mean weight decreased by roughly 10% or 12%.

In the 2.4 mg arm, 80% of participants experienced at least one adverse event. The proportion was 71% in both the 1.0 mg arm and the pooled placebo arm. Gastrointestinal problems predominated and usually had mild or moderate severity. Investigators saw no severe hypoglycemia. A cancer death in the 1.0 mg arm was assessed as unrelated to study treatment. Novo Nordisk supplied the funding.

What it means

This trial addresses a difficult point in diabetes care. Basal insulin may leave A1C above target and can be accompanied by weight gain or hypoglycemia. Under the study conditions, adding either CagriSema dose produced larger reductions in both A1C and weight than adding placebo.

REIMAGINE 3 is one part of a three-trial diabetes cluster. REIMAGINE 1 studied people using diet and exercise without glucose-lowering medicine, while REIMAGINE 2 compared the combination with its components in people taking metformin with or without an SGLT2 inhibitor. The trials should not be treated as interchangeable because they cover different treatment stages.

What it does not mean

Every control arm in REIMAGINE 3 received placebo rather than semaglutide, cagrilintide or a different active add-on. The study therefore cannot measure the contribution of each CagriSema component for patients using basal insulin. Finding no severe hypoglycemia in a trial of 274 people also cannot rule out that outcome in a larger population.

Forty weeks is too short to establish durable glucose control or effects on cardiovascular, kidney, eye or mortality outcomes. The findings apply most directly to adults who resemble the trial participants and should not be generalized to people who are not taking basal insulin.