Design and baseline characteristics of the CagriSema cardiovascular outcomes trial (REDEFINE 3)
- Design
- Randomized trial · 7076 participants · Hard outcome
- Match to healthy normal-weight adults aged 55–75
- Different populationINDIRECT: all participants had established cardiovascular disease and BMI ≥25.0 kg/m2; 76% had BMI ≥30 kg/m2 and 61% had type 2 diabetes; mean age 66 years.
- Could weight loss explain it?
- Not applicableNot applicable: a design and baseline report with no outcome yet, so there is no result whose mediation could be judged.
- Study tier
- Not ratedNOT_RATED: a design and baseline-characteristics report of a randomized trial, with no outcome data for CagriSema yet.
- Assessment
- Version 3 · Two reviewers differed; settled by a recorded ruling · Oct 19, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
This paper describes the design and starting characteristics of REDEFINE 3, a double-blind randomized trial of weekly CagriSema (cagrilintide plus semaglutide) against placebo in 7076 adults with established cardiovascular disease and BMI of at least 25.0. Mean age was 66 years, 76% had BMI of 30 or more, and 61% had type 2 diabetes. It reports no results on heart attacks, strokes or deaths yet.
01Findings
What the study reported
- Drugs
- Cagrilintide-semaglutide
- Dose
- CagriSema 2.4 mg/2.4 mg once weekly
- Route
- subcutaneous
- Comparator
- placebo, plus standard of care
- Primary outcome
- MACE-3 noninferiority (safety) and MACE-4 superiority (efficacy) versus placebo; this paper reports design and baseline only
- Effect
- not reported in abstract
- 95% confidence interval
- not reported in abstract
- Follow-up
- Not stated
- Adverse events
- not reported in abstract
- Limitations
- A design and baseline report with no outcome results yet, so no conclusion on cardiovascular safety or efficacy can be drawn; the population had established cardiovascular disease and excess weight, not normal weight.
Who was studied
- Mean age
- 66 years
- Bmi min
- 25
- Obesity status
- overweight or obesity required (BMI ≥25.0 kg/m2); BMI ≥30 kg/m2 in 76%
- Diabetes status
- mixed (with or without type 2 diabetes; 61% with T2D)
- Cvd status
- established cardiovascular disease required
- Ckd status
- not reported in abstract
- Baseline condition
- established cardiovascular disease with excess adiposity (BMI ≥25.0 kg/m2)
- Sample size
- 7076
- Inclusion exclusion
- established CVD and BMI ≥25.0 kg/m2, with or without T2D
Study quality details
- Study design
- Randomized controlled trial
- Sample size
- 7076
- Randomization
- yes
- Blinding
- double-blind
- Comparator
- placebo, plus standard of care
- Follow up duration
- not stated
- Outcome type
- hard
- Replication
- not assessed
- Consistency with other evidence
- not assessed
- Population applicability
- INDIRECT
- Statistical precision
- no outcome results; baseline characteristics only
- Risk of bias
- not assessed
- Funding conflicts
- yes
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- Novo Nordisk A S (financial support, as reported in the competing-interests declaration)
- Industry funded
- Yes
- Manufacturer
- Novo Nordisk A S
- Sponsor role
- not reported in abstract
- Author conflicts
- Several authors are Novo Nordisk employees with stock, and others report consulting, speaking, grant or employment relationships with Novo Nordisk, Eli Lilly and many other companies.
- Independent replication
- unknown
- Notes
- Authors declare relationships with the drug's manufacturer: Novo Nordisk A S (five authors report employment and equity or stocks).
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[IMPORTANCE] Cagrilintide-semaglutide (CagriSema) is a fixed-dose combination of the amylin receptor agonist cagrilintide and the glucagon-like peptide-1 receptor agonist semaglutide administered subcutaneously once weekly. CagriSema has demonstrated significant weight reduction and improved glycemic control in participants with excess adiposity and type 2 diabetes (T2D). [METHODS] REDEFINE 3 is a double-blind, randomized, placebo-controlled trial involving participants with established cardiovascular disease (CVD) and body mass index (BMI) ≥25.0 kg/m2 with/without T2D randomized to CagriSema 2.4 mg/2.4 mg or placebo, plus standard of care. The safety objective is to confirm noninferiority of CagriSema compared with placebo on cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE-3). The efficacy objective is to confirm the superiority of CagriSema compared with placebo on cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or revascularization (MACE-4). [RESULTS] Between 1/2023-12/2024, 7076 adults at 575 sites in 24 countries were randomized. Mean age at baseline was 66 years. BMI ≥30 kg/m2 was present in 76% of participants (n=5370). In participants with T2D (n=4348, 61%), the mean duration of T2D was 12 years and mean glycated hemoglobin was 7.7%. Most participants had a prior myocardial infarction (n=4369, 62%). Prior stroke (n=1311, 19%) and peripheral arterial disease (n=769, 11%) were less common, and 617 participants (9%) had more than one qualifying CVD criteria. [CONCLUSION] The REDEFINE 3 trial will provide evidence regarding the cardiovascular safety and efficacy of CagriSema, a novel fixed-dose combination therapy that could improve cardiovascular outcomes in a broad population of people with established CVD and excess adiposity. [TRIAL REGISTRATION] The REDEFINE 3 trial is registered at ClinicalTrials.gov (NCT05669755).