CagriSema phase 3: what the REDEFINE trials have reported so far
Prepared by: Research Desk. Sources are linked for verification.
Published 25 October 2026
At a glance
- What it is: CagriSema is an investigational combination of cagrilintide, a long-acting amylin analogue, and semaglutide, a GLP-1 receptor agonist, developed by Novo Nordisk
- Phase 3 programme: the REDEFINE trials, which compare the combination with placebo, with its components or with semaglutide alone
- Published so far: REDEFINE 1 and REDEFINE 2 in the New England Journal of Medicine (2025), and REDEFINE 5, run in Japan and Taiwan, in The Lancet Diabetes & Endocrinology (2026)
- Newest record: the design and baseline characteristics of REDEFINE 3, a cardiovascular outcomes trial in 7,076 adults, published in the American Heart Journal in October 2026
- Status: CagriSema remains investigational in this record; cardiovascular outcome results have not yet been published
REDEFINE 1: adults with overweight or obesity
Garvey et al. (2025) reported a 68-week, double-blind, placebo-controlled trial (NCT05567796) in adults with a body-mass index of at least 30, or at least 27 with at least one weight-related condition, and without diabetes. A total of 3,417 participants were randomly assigned to CagriSema, placebo, cagrilintide alone or semaglutide alone.
- Primary result: mean change in body weight from baseline to week 68 was −20.4% with CagriSema and −3.0% with placebo, an estimated difference of −17.3 percentage points (95% CI −18.1 to −16.6)
- Adverse events: gastrointestinal adverse events were reported in 79.6% of the CagriSema group and 39.9% of the placebo group; most were described as transient and mild to moderate
- Funding: the trial was funded by Novo Nordisk
A post hoc analysis of the same trial, published in Hypertension (Verma et al., 2026), reported a mean change in systolic blood pressure of −10.9 mmHg with CagriSema and −2.8 mmHg with placebo. A further post hoc analysis in Diabetes, Obesity and Metabolism (Busetto et al., 2026) looked at waist and other anthropometric targets. Post hoc analyses were not the trial's primary question and are best read as exploratory.
REDEFINE 2: adults with obesity and type 2 diabetes
Davies et al. (2025), published alongside REDEFINE 1, reported a 68-week trial (NCT05394519) in 1,206 adults in 12 countries with type 2 diabetes and a body-mass index of at least 27, randomly assigned in a 3:1 ratio to CagriSema or placebo.
- Primary result: mean change in body weight was −13.7% with CagriSema and −3.4% with placebo, an estimated difference of −10.4 percentage points (95% CI −11.2 to −9.5)
- Glycaemic measure: 73.5% of the CagriSema group and 15.9% of the placebo group reached a glycated haemoglobin of 6.5% or less
- Adverse events: gastrointestinal adverse events were reported in 72.5% and 34.4% of the two groups
As in other trials of this drug class, the weight reduction in participants with type 2 diabetes was smaller than in REDEFINE 1.
REDEFINE 5: a head-to-head trial in East Asia
Yamauchi et al. (2026) reported REDEFINE 5 (NCT05813925), a double-blind trial at 21 sites in Japan and one in Taiwan that compared CagriSema directly with semaglutide alone in 331 adults with overweight or obesity.
- Primary result: mean change in body weight was −18.4% with CagriSema and −11.9% with semaglutide, an estimated difference of −6.5 percentage points (95% CI −8.4 to −4.6)
- Why it matters for researchers: it is the first published REDEFINE trial with an active comparator as the main contrast, which isolates the added effect of cagrilintide in this population
Unlike REDEFINE 1 and 2, the REDEFINE 5 paper uses the trial product estimand as its primary analysis, which assumes the product was taken as intended. That figure is not directly comparable with the primary figures from the two NEJM trials.
REDEFINE 3: the cardiovascular outcomes trial
The newest entry in the record is a design paper rather than a result. Cavender et al. (2026), in the American Heart Journal, describe REDEFINE 3 (NCT05669755), which randomised 7,076 adults with established cardiovascular disease and a body-mass index of 25 or more, with or without type 2 diabetes, at 575 sites in 24 countries between January 2023 and December 2024. Mean age at baseline was 66 years, and 62% had a prior heart attack.
- Primary question: whether CagriSema is non-inferior to placebo for three-point major adverse cardiovascular events (cardiovascular death, non-fatal heart attack or non-fatal stroke)
- Secondary question: whether it is superior to placebo on a four-point composite that adds coronary revascularisation
- Status: event-driven; no outcome results had been published at the time of writing
How this fits the wider pipeline
KlowSignal has covered retatrutide's TRIUMPH phase 3 papers, which tested a single molecule acting on three receptors. CagriSema takes a different route, pairing two separate peptides, an amylin analogue and a GLP-1 receptor agonist, in one product. Direct comparisons between the two programmes are not possible from the published record: the trials differ in duration, populations, comparators and analysis methods.
Limitations of the evidence
- Single sponsor: all four papers come from trials funded by the developer, with company employees among the authors
- Estimands: REDEFINE 1 and 2 report their primary figures under an estimand that keeps every randomised participant in the analysis whether or not they stopped the product, while REDEFINE 5 uses the trial product estimand, so the headline figure depends on how discontinuation is handled; compare like with like
- Duration: 68 weeks is long for a weight trial but short for questions about durability, and REDEFINE 3 has not reported
- Generalisability: REDEFINE 5 enrolled only participants in Japan and Taiwan, so its results may not transfer directly to other populations
- Not a research reagent: the trial product is a pharmaceutical formulation; findings say nothing about the identity, purity or behaviour of research-grade cagrilintide or semaglutide
Key terms
- Amylin analogue: a peptide designed to mimic amylin, a hormone released with insulin by the pancreas
- GLP-1 receptor agonist: a compound that activates the glucagon-like peptide-1 receptor
- Non-inferiority: a trial design that tests whether a new product is not worse than a comparator by more than a pre-set margin
- MACE: major adverse cardiovascular events, a standard composite outcome in cardiovascular trials
Record dates: 22 June 2025 (REDEFINE 1 and 2 online), 17 April 2026 (REDEFINE 5 online), 6 October 2026 (REDEFINE 3 design). Status last checked: 25 October 2026.
Supplier
Purita is a store that sells peptides for laboratory research use only. It does not list CagriSema, which is an investigational pharmaceutical product; the link below goes to the store's homepage.
Affiliate disclosure: this is a paid link. KlowSignal earns a commission if a purchase is made through it, at no extra cost to the buyer. A listing is not an endorsement or a statement about product quality. See the affiliate disclosure.
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