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REDEFINE 3 Trial Enrolls 7,076 Adults to Test CagriSema on Cardiovascular Outcomes
The REDEFINE 3 trial has completed enrollment of 7,076 adults with established cardiovascular disease and excess adiposity, randomizing participants to the fixed-dose combination CagriSema or placebo in the first large-scale cardiovascular outcomes trial for this dual receptor agonist. No outcomes data are yet available; this report describes the trial design and baseline characteristics of the enrolled cohort.
What Was Studied
REDEFINE 3 is investigating whether cagrilintide-semaglutide (CagriSema) — a once-weekly subcutaneous combination of an amylin receptor agonist and a GLP-1 receptor agonist — is cardiovascularly safe and whether it can reduce the occurrence of major adverse cardiovascular events in adults with established cardiovascular disease and a BMI of at least 25 kg/m². The trial carries a dual mandate: a safety objective requiring noninferiority on a three-component composite endpoint (MACE-3), and an efficacy objective requiring superiority on a four-component composite that additionally includes revascularization (MACE-4).
How It Was Studied
REDEFINE 3 is a double-blind, randomized, placebo-controlled trial conducted between January 2023 and December 2024 at 575 clinical sites across 24 countries. A total of 7,076 adults were enrolled and assigned to either CagriSema 2.4 mg/2.4 mg once weekly plus standard of care, or placebo plus standard of care. Eligible participants were required to have established cardiovascular disease and a BMI of 25.0 kg/m² or greater, and could be enrolled with or without a diagnosis of type 2 diabetes. The trial remains ongoing, and no event-based outcome data have been reported in this publication.
What Was Observed
- The enrolled population skewed toward higher adiposity: three-quarters of participants had a BMI at or above 30 kg/m² (76%; n=5,370), indicating that the majority meet the conventional definition of obesity rather than merely overweight status.
- Type 2 diabetes was present in 61% of participants (n=4,348), and among this subgroup, the average diabetes duration was 12 years with a mean glycated hemoglobin of 7.7%, reflecting a population with established and incompletely controlled disease.
- Prior myocardial infarction was the dominant qualifying cardiovascular event, present in 62% of participants (n=4,369). Prior stroke was documented in 19% (n=1,311), peripheral arterial disease in 11% (n=769), and 9% of participants (n=617) met more than one qualifying cardiovascular criterion, indicating substantial clinical complexity in a meaningful subset.
- The mean age at enrollment was 66 years, situating this as a predominantly older adult cohort with a high burden of pre-existing cardiometabolic and vascular disease.
Why This Matters
CagriSema combines two distinct receptor-targeting mechanisms — amylin receptor agonism and GLP-1 receptor agonism — in a single fixed-dose formulation that has already demonstrated meaningful weight reduction and glycemic improvement in earlier trials. Whether these metabolic benefits translate into reduced cardiovascular events in a high-risk population with established CVD has not previously been tested at scale. REDEFINE 3 represents the first trial designed explicitly to answer that question, and its broad enrollment — spanning participants with and without diabetes across a wide range of qualifying CVD categories — will allow assessment of CagriSema’s cardiovascular profile in a clinically heterogeneous population.
How to Read This Result
This publication reports only trial design and baseline characteristics; no efficacy or safety outcome data are yet available, and conclusions about CagriSema’s cardiovascular effects must await final results after sufficient event accrual and follow-up are achieved.
Limitations
The abstract does not explicitly report study limitations.