REDEFINE 2: CagriSema for obesity in people with type 2 diabetes

REDEFINE 2 is the diabetes companion to REDEFINE 1, published in the same issue. It drops the monotherapy arms and adds glycaemic endpoints.

What the trial asked

Whether once-weekly cagrilintide 2.4 mg plus semaglutide 2.4 mg reduces body weight compared with placebo in adults with type 2 diabetes and a BMI of 27 or higher.

Design

Phase 3a, double-blind, randomised 3:1, placebo-controlled, 68 weeks, in 12 countries. CagriSema (2.4 mg of each) versus placebo, with lifestyle intervention. Two primary endpoints: percent change in body weight, and the percentage with a reduction of at least 5 percent. Treatment-policy estimand. A subgroup wore continuous glucose monitors.

Who was enrolled

1206 adults with a BMI of 27 or more, HbA1c 7 to 10 percent, and type 2 diabetes: 904 to CagriSema, 302 to placebo. Baseline weight is not stated in the abstract.

Primary endpoint and result

Estimated mean change in body weight at week 68: -13.7 percent with CagriSema versus -3.4 percent with placebo. Estimated difference -10.4 percentage points (95% CI -11.2 to -9.5; P less than 0.001). More patients on CagriSema reached 5 percent, and also 10, 15 and 20 percent (P less than 0.001); percentages are not in the abstract.

Key secondary results

HbA1c of 6.5 percent or lower was reached by 73.5 percent on CagriSema and 15.9 percent on placebo.

Adverse events and discontinuation

Gastrointestinal adverse events in 72.5 percent on CagriSema versus 34.4 percent on placebo, mostly transient and mild or moderate. The abstract does not give discontinuation rates.

Funding and registration

Novo Nordisk. ClinicalTrials.gov NCT05394519.

What this trial does not show

• Placebo-controlled only. There is no semaglutide-alone arm here, so the trial cannot say what cagrilintide adds in people with diabetes.
• The weight result (-13.7 percent) is about two-thirds of REDEFINE 1's -20.4 percent in people without diabetes, which is the same ratio seen with semaglutide alone in STEP 2 versus STEP 1.
• No cardiovascular or kidney outcomes; 68 weeks only.
• CagriSema is investigational and not approved.

Where the numbers come from

PubMed abstract of the primary paper (PubMed 40544432), fetched 4 September 2026.