REDEFINE 3: CagriSema Trial Design

The new REDEFINE 3 paper describes how the CagriSema cardiovascular outcomes trial is built and who entered it. It reports 7,076 adults randomized between January 2023 and December 2024, but it reports no heart attack, stroke, death, or treatment-effect result.^[1] Cardiovascular outcomes remain pending while the phase 3 trial continues.

CagriSema is a fixed-dose combination of cagrilintide, an amylin receptor agonist, and semaglutide, a GLP-1 receptor agonist. REDEFINE 3 compares once-weekly CagriSema with placebo on top of standard care in people who already have cardiovascular disease and a body mass index of at least 25 kg/m².^[1] The study includes people with and without type 2 diabetes.

The paper is a baseline report

A baseline paper freezes the participant profile near the start of a study. It can show whether the enrolled group matches the research question and whether major clinical subgroups are represented. It cannot show whether CagriSema prevents an event because the randomized groups have not yet been compared on the planned outcomes in this publication.^[1]

That boundary matters here. The abstract labels its numerical section as results because baseline characteristics are study results in a technical sense. Those numbers describe age, body size, diabetes history, and existing cardiovascular disease. They are not efficacy or safety findings for CagriSema. The ClinicalTrials.gov record also states that no results have been posted.^[2]

The trial is randomized, placebo-controlled, and blinded. The publication describes two linked cardiovascular questions. Its safety objective tests whether CagriSema is not unacceptably worse than placebo for a three-part composite called MACE-3: cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Its efficacy objective tests superiority on MACE-4, which adds revascularization, a procedure that restores blood flow.^[1]

Who entered REDEFINE 3

Participants had a mean age of 66 years. Three quarters, 76% or 5,370 people, had a body mass index of at least 30 kg/m². Type 2 diabetes was present in 4,348 participants, or 61%. Within that subgroup, diabetes had lasted a mean of 12 years and mean HbA1c, a measure of average blood glucose over roughly three months, was 7.7%.^[1]

Existing cardiovascular disease was required. A previous myocardial infarction was the qualifying history for 4,369 participants, or 62%. The paper reports prior stroke in 1,311 people, or 19%, and peripheral arterial disease in 769, or 11%. Another 617 participants, 9%, met more than one qualifying cardiovascular criterion.^[1]

This is therefore a high-risk secondary-prevention population. The trial is asking about additional events among older adults who already have established cardiovascular disease, not about first-event prevention in otherwise healthy adults. Results will not automatically apply to younger people, those with lower body mass index, or people without known cardiovascular disease.

What the trial will measure

The current registry names time to first MACE-3 as the primary outcome, measured from baseline through the end of study. It also lists kidney outcomes, body weight, waist measures, blood pressure, blood lipids, HbA1c, serious adverse events, malignant neoplasms, and severe hypoglycemia among the secondary measures.^[2] These are planned measurements. A registry outcome list does not tell us which direction any result will take.

ClinicalTrials.gov classifies REDEFINE 3 as active but not recruiting. The record was verified in August 2026 and estimates primary completion in September 2027, with study completion in October 2027. It lists 7,101 as actual enrollment, while the paper reports 7,076 randomized participants in its baseline analysis.^[2][1] The public records do not explain that 25-person difference, so the two figures should not be treated as interchangeable.

The registry says participants receive study treatment for up to 235 weeks, including a 16-week dose-escalation period in the active arm. The primary cardiovascular outcome is followed for up to 242 weeks or more.^[2] These are protocol details, not dosing instructions. Treatment decisions involving semaglutide or any investigational combination require a qualified clinician.

Why the baseline mix matters

The mix of diabetes status and qualifying cardiovascular conditions will shape how readers interpret the eventual event rates. A population dominated by prior myocardial infarction may have a different underlying risk profile from one dominated by prior stroke or peripheral arterial disease. The planned randomized comparison should balance measured and unmeasured characteristics between treatment groups, but the published abstract gives the combined cohort rather than arm-by-arm baseline tables.

The trial also combines an amylin pathway drug with a medicine already covered in our semaglutide evidence overview. That makes cardiovascular safety and event adjudication central to the design. Readers looking for known semaglutide adverse effects can use our semaglutide safety section, but those data cannot substitute for CagriSema results from REDEFINE 3.

Novo Nordisk sponsors REDEFINE 3. The paper's disclosure states that Novo Nordisk provided financial support, and several coauthors reported company employment and stock or equity interests.^[1] Sponsorship does not decide the outcome, but it belongs in any reading of the design, analysis, and eventual report.

What we do not know yet

The publication does not establish that CagriSema lowers cardiovascular risk, confirms cardiovascular safety, causes weight loss in this population, or improves kidney outcomes. It provides the protocol logic and the cohort profile needed to judge those claims later. Event counts, hazard ratios, confidence intervals, adverse-event comparisons, treatment discontinuations, and subgroup effects are still unavailable.

The next meaningful evidence will be a results report that preserves the randomized comparison and explains how events were adjudicated, how missing data were handled, and whether the statistical tests followed the prespecified order. Until then, REDEFINE 3 should be described as an ongoing cardiovascular outcomes trial with published design and baseline characteristics.

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