Design and baseline characteristics of the CagriSema cardiovascular outcomes trial (REDEFINE 3).
The REDEFINE 3 trial is designed to assess the cardiovascular safety and efficacy of CagriSema in a high-risk population with established cardiovascular disease and excess adiposity.
Where it sits
this study against the rest of the cagrilintide (am833) corpusSummary and findings
The REDEFINE 3 trial investigates the cardiovascular outcomes of Cagrilintide-semaglutide (CagriSema) in participants with established cardiovascular disease and a body mass index of 25.0 kg/m² or higher. Participants were randomized to receive either CagriSema 2.4 mg/2.4 mg or placebo, plus standard of care. The study aims to assess the noninferiority and superiority of CagriSema regarding major adverse cardiovascular events.
Abstract
<h4>Importance</h4>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).<h4>Methods</h4>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/m<sup>2</sup> 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).<h4>Results</h4>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/m<sup>2</sup> 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.<h4>Conclusion</h4>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.<h4>Trial registration</h4>The REDEFINE 3 trial is registered at ClinicalTrials.gov (NCT05669755).
Background
The study addresses the cardiovascular safety and efficacy of Cagrilintide-semaglutide (CagriSema), a combination therapy for individuals with established cardiovascular disease and excess adiposity. Prior research has indicated that both amylin receptor agonists and GLP-1 receptor agonists can influence weight and glycemic control. This trial is significant as it aims to provide evidence on cardiovascular outcomes in a population at high risk for cardiovascular events.
Methods
REDEFINE 3 is a double-blind, randomized, placebo-controlled trial involving 7076 adults with established cardiovascular disease and BMI ≥25.0 kg/m². Participants are randomized to receive either CagriSema 2.4 mg/2.4 mg or placebo, plus standard of care. The primary outcome measures include cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE-3), while secondary outcomes assess cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or revascularization (MACE-4).
Results
The trial enrolled 7076 participants, with a mean age of 66 years. Among participants, 76% had a BMI ≥30 kg/m², and 61% had type 2 diabetes with a mean duration of 12 years. The mean glycated hemoglobin for those with T2D was reported as 7.7%. Prior myocardial infarction was present in 62% of participants.
Interpretation
The findings indicate a significant proportion of participants with obesity and type 2 diabetes, which aligns with the high-risk profile for cardiovascular events. While the study design is robust, the results are still pending, and the clinical significance of the outcomes will depend on the final analysis. Potential confounds include the ongoing nature of the trial and lack of reported outcomes at this stage.
Key findings
- 7076 adults randomized between 1/2023-12/2024.
- Mean age at baseline was 66 years.
- 76% of participants had BMI ≥30 kg/m² (n=5370).
- 61% of participants had type 2 diabetes (n=4348) with a mean duration of 12 years.
- Mean glycated hemoglobin was 7.7% in participants with T2D.
- 62% of participants had a prior myocardial infarction (n=4369).
Limitations
- Ongoing trial, results not yet available.
- No specific outcomes or statistical analyses reported in abstract.
- Large sample size but lacks interim results.
- No details on follow-up duration or specific cardiovascular event rates.