REDEFINE 1: CagriSema (cagrilintide plus semaglutide) for obesity

Cagrilintide is a long-acting amylin analogue. CagriSema pairs it with semaglutide in one weekly injection. REDEFINE 1 is the pivotal obesity trial and, unusually, it kept both monotherapies in the design.

What the trial asked

Whether cagrilintide 2.4 mg plus semaglutide 2.4 mg reduces body weight compared with placebo in adults with obesity, or overweight with a complication, who do not have diabetes.

Design

Phase 3a, 68 weeks, multicentre, double-blind, placebo- and active-controlled. Randomised 21:3:3:7 to CagriSema (semaglutide 2.4 mg with cagrilintide 2.4 mg), semaglutide 2.4 mg alone, cagrilintide 2.4 mg alone, or placebo, all with lifestyle intervention. Coprimary endpoints: relative change in body weight, and reduction of 5 percent or more, from baseline to week 68, CagriSema versus placebo. Reductions of 20, 25 and 30 percent or more were confirmatory secondary endpoints. Treatment-policy estimand.

Who was enrolled

3417 adults with a BMI of 30 or higher, or 27 or higher with at least one obesity-related complication, without diabetes. 2108 assigned to CagriSema, 302 to semaglutide, 302 to cagrilintide, 705 to placebo. Baseline weight is not stated in the abstract.

Primary endpoint and result

Estimated mean percent change in body weight at week 68: -20.4 percent with CagriSema versus -3.0 percent with placebo. Estimated difference -17.3 percentage points (95% CI -18.1 to -16.6; P less than 0.001). CagriSema participants were more likely than placebo to reach 5, 20, 25 and 30 percent reductions (P less than 0.001 for all); the abstract does not give the percentages.

The semaglutide-alone and cagrilintide-alone arm results are not in the abstract. They are in the full paper, and this site does not report numbers it has not read in the source it cites, so the explorer lists those arms without a bar.

Key secondary results

None quantified in the abstract beyond the responder statements above.

Adverse events and discontinuation

Gastrointestinal adverse events (nausea, vomiting, diarrhoea, constipation, abdominal pain) affected 79.6 percent on CagriSema and 39.9 percent on placebo, mainly transient and mild to moderate. The abstract does not give discontinuation rates.

Funding and registration

Novo Nordisk. ClinicalTrials.gov NCT05567796.

What this trial does not show

• Without the monotherapy numbers from the abstract, this page cannot tell you how much cagrilintide adds on top of semaglutide 2.4 mg. That comparison exists in the full paper and is the whole point of the design.
• -20.4 percent at 68 weeks sits close to tirzepatide 15 mg in SURMOUNT-1 (-20.9 percent at 72 weeks). Different trials, different estimands (treatment-policy here, treatment-regimen there), no head-to-head.
• CagriSema is investigational. It is not approved and not available as a prescription product.
• Nothing on durability, withdrawal, or hard outcomes.

Where the numbers come from

PubMed abstract of the primary paper (PubMed 40544433), fetched 4 September 2026. The diabetes trial is REDEFINE 2.