Key facts
- Drug / target: CagriSema — cagrilintide 2.4 mg (long-acting amylin analogue) plus semaglutide 2.4 mg (GLP-1 receptor agonist), once-weekly subcutaneous injection.
- Sponsor: Novo Nordisk.
- Design: randomized, double-blind, placebo-controlled, phase 3.
- Population: adults with overweight or obesity without type 2 diabetes; 3,417 randomized.
- Duration: 68 weeks.
- Primary endpoint: percentage change in body weight from baseline to week 68.
- Headline result: −20.4% with CagriSema vs −3.0% placebo (treatment-policy estimand); difference −17.3 percentage points (95% CI −18.1 to −16.6).
- Registration: NCT05567796 (ClinicalTrials.gov).
- Publication: New England Journal of Medicine, 2025 — PMID 40544433.
- Approval status: investigational; not approved by any regulator.
What was the REDEFINE 1 trial?
REDEFINE 1 was a phase 3, randomized, double-blind, placebo-controlled trial run by Novo Nordisk to test whether combining two appetite-regulating peptides produces greater weight loss than placebo in people with obesity.
The combination, called CagriSema, pairs cagrilintide — a long-acting analogue of the pancreatic hormone amylin — with semaglutide, the GLP-1 receptor agonist already marketed as Wegovy and Ozempic. Because amylin and GLP-1 signal satiety through partly separate pathways, the hypothesis was that giving both would suppress appetite more than either hormone alone. The trial was registered as NCT05567796 and published in the New England Journal of Medicine in 2025 (PMID 40544433). It is one study within the wider phase 3 REDEFINE program.
Who was in it?
REDEFINE 1 randomized 3,417 adults with overweight or obesity who did not have type 2 diabetes. That exclusion matters: weight-loss results in people without diabetes are typically larger than in people with it, so REDEFINE 1 measures CagriSema in the population where the drug class tends to perform best. Participants were split across four arms — the CagriSema combination, semaglutide alone, cagrilintide alone, and placebo — with the largest group receiving the combination. As in the other landmark obesity trials, all arms received the same lifestyle guidance, so the placebo arm shows what diet and activity support achieved on their own.
What did participants receive?
The active arm received CagriSema as a single once-weekly subcutaneous injection delivering cagrilintide 2.4 mg and semaglutide 2.4 mg. The comparator arm received matching placebo. This section reports what the trial administered; it is not a dosing instruction, and nothing here should be read as guidance on what any reader should take. Doses in a trial are escalated and monitored under a study protocol, which is not the same as self-administration.
Primary results
The primary endpoint was the percentage change in body weight from baseline to week 68. Using the treatment-policy estimand — which counts all randomized participants regardless of whether they stayed on treatment — the mean change was −20.4% with CagriSema versus −3.0% with placebo. The estimated treatment difference was −17.3 percentage points (95% CI −18.1 to −16.6; P<0.001).
The estimand label is not a technicality. The treatment-policy estimand reflects the effect of being assigned to CagriSema in a real-world sense, including people who reduced or stopped the drug; a trial-product estimand — the effect if everyone had stayed fully adherent — would typically be somewhat larger. Reporting the treatment-policy figure is the conservative, regulator-aligned way to state the headline number.
Secondary results
Beyond the mean, REDEFINE 1 reported that participants on CagriSema were significantly more likely than those on placebo to reach weight-loss thresholds of 5% or more, 20% or more, 25% or more, and 30% or more (P<0.001 for each comparison). The published abstract does not attach a single percentage to each of those thresholds, so this page states the direction of the result rather than an unverified figure.
| Measure (week 68) | CagriSema | Placebo |
|---|---|---|
| Mean change in body weight (treatment-policy estimand) | −20.4% | −3.0% |
| Estimated treatment difference | −17.3 percentage points (95% CI −18.1 to −16.6; P<0.001) | |
| Reached ≥5%, ≥20%, ≥25% and ≥30% weight loss | Significantly more likely with CagriSema than placebo (P<0.001 for each; per-threshold percentages not given in the abstract) | |
Safety and side effects reported
Gastrointestinal effects were the most common adverse events, consistent with the GLP-1 drug class. They were reported in 79.6% of the CagriSema group versus 39.9% of the placebo group and included nausea, vomiting, diarrhea, constipation and abdominal pain. The trial described these events as mainly transient and mild-to-moderate. GI symptoms in this class are generally worst during dose escalation and ease as the dose stabilizes, which is one reason titration in obesity trials is deliberately slow.
As always, an investigational combination carries less long-term safety data than an approved, marketed drug. The absence of a long post-marketing record is itself a limitation, not a reassurance.
Limitations and what it does not prove
- It is a single trial. REDEFINE 1 measures 68-week weight change in one population. It is not a cardiovascular outcomes trial and does not establish long-term benefit on heart attacks, strokes or mortality.
- The population was specific. Enrollees had overweight or obesity without type 2 diabetes. Results in people with diabetes, or with other conditions, are studied separately and are typically different.
- Investigational status. CagriSema is not approved by any regulator. A completed phase 3 trial supports a regulatory submission; it is not the same as an approval, a label, or confirmation of long-term safety.
- Means are not personal predictions. The −20.4% figure is an average across an arm. Individual responses in obesity trials span a wide range, and this page reports the trial, not an expected outcome for any reader.
- Cross-trial comparisons are imperfect. Putting the 20.4% figure next to numbers from other weight-loss trials is informative but not a head-to-head; only a direct randomized comparison settles which drug is superior.
Why the REDEFINE 1 trial matters
REDEFINE 1 is the pivotal phase 3 readout for the first amylin-plus-GLP-1 combination to reach that stage, and its roughly 20% mean weight loss puts CagriSema in the same territory as tirzepatide and above the semaglutide monotherapy benchmark from STEP 1. It is evidence that stacking a second satiety hormone onto GLP-1 can add meaningful effect, echoing the broader direction of obesity pharmacology toward multi-hormone agents such as retatrutide. For readers mapping the field, it sits alongside the pillar overview of which weight-loss peptides have real human trial data and the comparison of the newest triple and dual agonists in retatrutide vs tirzepatide.
The equally important takeaway is the gap between a strong trial result and a treatment you can obtain. CagriSema is investigational. Until a regulator reviews and approves it, its real-world efficacy, tolerability and long-term safety in the general population remain unproven, and any product sold under its name is unapproved and unverified. The trial redefines what is achievable; it does not create an available medicine.
Frequently asked questions
What was the REDEFINE 1 trial?
REDEFINE 1 was a phase 3, randomized, double-blind, placebo-controlled trial sponsored by Novo Nordisk. It tested once-weekly CagriSema — cagrilintide 2.4 mg plus semaglutide 2.4 mg — against placebo for weight management in adults with overweight or obesity who did not have type 2 diabetes, over 68 weeks. It is registered as NCT05567796 and was published in the New England Journal of Medicine in 2025.
What is CagriSema?
CagriSema is an investigational fixed combination of two peptides given as one once-weekly subcutaneous injection: cagrilintide, a long-acting amylin analogue, and semaglutide, a GLP-1 receptor agonist. The two hormones suppress appetite through partly different pathways, which is the rationale for combining them. CagriSema is not approved by any regulator.
How much weight did people lose in REDEFINE 1?
Using the treatment-policy estimand, the mean change in body weight from baseline to week 68 was 20.4% with CagriSema versus 3.0% with placebo — a difference of 17.3 percentage points (95% CI −18.1 to −16.6). These are mean changes across the trial arms, not a result any individual should expect.
Is CagriSema approved?
No. As of 2026, CagriSema is investigational and is not approved by the FDA, the EMA, the MHRA, the TGA or any other regulator. REDEFINE 1 is one trial in the phase 3 REDEFINE program, but completing pivotal trials is not the same as approval. Vials sold online under the CagriSema, cagrilintide or semaglutide names outside a prescription are unapproved products of unverified identity, purity and dose.
What were the main side effects in REDEFINE 1?
Gastrointestinal effects were the most common adverse events, reported in 79.6% of the CagriSema group versus 39.9% of the placebo group. They included nausea, vomiting, diarrhea, constipation and abdominal pain, and were described as mainly transient and mild-to-moderate. This mirrors the tolerability profile seen across GLP-1-based obesity drugs.
Did REDEFINE 1 include people with type 2 diabetes?
No. REDEFINE 1 enrolled adults with overweight or obesity who did not have type 2 diabetes. CagriSema has been studied separately in people with type 2 diabetes in other trials within the REDEFINE program, but those results are reported elsewhere and are not part of REDEFINE 1.
Sources
This summary traces to the peer-reviewed publication and trial registration:
- Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity — New England Journal of Medicine, 2025; PubMed 40544433.
- REDEFINE 1 (CagriSema) — ClinicalTrials.gov NCT05567796.
- Drug reference records: cagrilintide and semaglutide.