CagriSema is the drug most often named as the next step after Wegovy. It is two molecules in one weekly pen — semaglutide, the GLP-1 medicine already sold as Wegovy and Ozempic, and cagrilintide, a long-acting analogue of amylin, a hormone that pancreatic beta cells release alongside insulin. It is not approved. This page reads what has actually been published and filed, as of 25 September 2026.
For the pipeline drug people compare it with most, see our retatrutide page; for the approved drug that beat it head to head, Zepbound's side effects and the tirzepatide versus semaglutide comparison.
Where it stands with the FDA
| Date | Event | Source |
|---|---|---|
| 22 June 2025 | REDEFINE 1 and REDEFINE 2 published | N Engl J Med 2025;393:635–659 |
| 18 December 2025 | New Drug Application submitted for weight management, based on REDEFINE 1 and 2 | Novo Nordisk announcement |
| 23 February 2026 | REDEFINE 4 misses its non-inferiority endpoint against tirzepatide | Novo Nordisk, SEC Form 6-K |
| 25 September 2026 | No CagriSema or cagrilintide entry in Drugs@FDA | our check of FDA's openFDA data |
Novo's filing announcement said the FDA "is expected to review the CagriSema application in 2026". It did not give a decision date, and none has been announced. If approved, Novo describes it as the first injectable combination of a GLP-1 receptor agonist and an amylin analogue.
The amylin half has an awkward precedent. The only amylin analogue ever approved in the US is pramlintide (Symlin, NDA 021332, approved 16 March 2005, a mealtime injection for people using insulin). FDA's Drugs@FDA record now lists every Symlin product as discontinued. CagriSema would bring the hormone back in a very different form: once a week, fixed-dose, in the same pen as semaglutide.
What the pivotal trials found
| Trial | Who | Length | CagriSema | Placebo | Excess over placebo |
|---|---|---|---|---|---|
| REDEFINE 1 | 3,417 adults, BMI ≥30 or ≥27 with a complication, no diabetes | 68 weeks | −20.4% | −3.0% | 17.3 points |
| REDEFINE 2 | 1,206 adults with type 2 diabetes, BMI ≥27 | 68 weeks | −13.7% | −3.4% | 10.4 points |
Both figures use the treatment-policy estimand — everyone randomised, whether or not they kept taking the drug. Novo's filing announcement also quotes the "if everyone stayed on treatment" figure for REDEFINE 1: 22.7% against 2.3%.
The diabetes gap is the finding most summaries skip. Measured against its own placebo, CagriSema's effect in people with type 2 diabetes was about 60% of its effect in people without it (10.4 against 17.3 points, our arithmetic from the two abstracts). The same pattern shows in the approved drugs' own trials — our before-and-after page found type 2 diabetes roughly halving the share of people who lose 20% or more on both semaglutide and tirzepatide — so it is not peculiar to CagriSema. It does mean the headline 20% belongs to one population.
REDEFINE 1 also randomised smaller groups to semaglutide alone and cagrilintide alone (302 each, in a 21:3:3:7 design), which is what lets the trial speak to whether the combination adds anything. The abstract reports the comparison with placebo; the single-drug arms are in the full paper.
A separate trial in Japan and Taiwan, REDEFINE 5 (331 people), compared CagriSema directly with semaglutide 2.4 mg alone: −18.4% against −11.9% at 68 weeks, a 6.5-point difference, using the estimand that assumes everyone took the drug as intended.
The head-to-head it lost
REDEFINE 4 put CagriSema against tirzepatide 15 mg — Zepbound's top dose — for 84 weeks in 809 people, open-label. Novo's own filing reports:
| Estimand | CagriSema | Tirzepatide 15 mg | Gap |
|---|---|---|---|
| If everyone stayed on treatment | 23.0% | 25.5% | 2.5 points |
| Counting people who stopped | 20.2% | 23.6% | 3.4 points |
The trial did not show non-inferiority. The gap is wider under the estimand that counts people who stopped treatment, which is the one closer to what happens to a whole group. Novo has said a phase 3 trial of a higher CagriSema dose would start in the second half of 2026, and that REDEFINE 11, exploring the current dose's "full weight-loss potential", would report in the first half of 2027. How Zepbound compares with the other approved options is on our best GLP-1 for weight loss page.
Side effects, as far as they are known
There is no US label, so there is no official adverse-reaction table. The published trials report:
- Gastrointestinal events — nausea, vomiting, diarrhoea, constipation, abdominal pain — in 79.6% on CagriSema against 39.9% on placebo (REDEFINE 1) and 72.5% against 34.4% (REDEFINE 2), described by the authors as mainly transient and mild to moderate.
- In REDEFINE 5, adverse events of any kind in 87% on CagriSema against 84% on semaglutide alone; 10% stopped CagriSema against 6% semaglutide.
Semaglutide's own label record is on our Wegovy side effects page. What the amylin half adds over years is not known: the long trials have not reported.
What the registry shows is still unpublished
On 25 September 2026, 44 studies listing cagrilintide as an intervention were registered on ClinicalTrials.gov: 22 phase 3, 5 phase 2, 17 phase 1. One of the 44 — a 92-person phase 2 trial that finished in 2022 — has posted results on the registry itself. The rest report through journals and company announcements, or have not reported.
Still running:
- REDEFINE 3, the cardiovascular outcomes trial, 7,101 people, primary completion listed for September 2027. Until it reports, CagriSema has no heart-outcome evidence of the kind behind Wegovy's heart indication.
- A trial in children and adolescents (primary completion listed for 2030), a long-term weight study, and smaller studies of muscle and bone.
Two studies comparing new versions of the injection, one phase 2 and one phase 3, were withdrawn before enrolling anyone.
What this page cannot tell you
- When, or whether, it will be approved, and at what price. Neither has been announced.
- How it will be dosed on a label. The filed product is 2.4 mg of each drug weekly; the escalation schedule will be set by the label if one is issued. Per-compound dosage reporting for cagrilintide on its own is on Peptifact's cagrilintide dosage page, and the molecule's entry is in the Peptide Lexicon.
- Whether it suits anyone. It is an investigational drug; questions about current options belong with a prescriber.
Sources
- Garvey WT et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). N Engl J Med 2025;393(7):635–647. doi:10.1056/NEJMoa2502081, abstract (PubMed 40544433). Funded by Novo Nordisk.
- Davies MJ et al. Cagrilintide–semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2). N Engl J Med 2025;393(7):648–659. doi:10.1056/NEJMoa2502082, abstract (PubMed 40544432).
- Yamauchi T et al. REDEFINE 5, cagrilintide–semaglutide versus semaglutide in an east Asian population. Lancet Diabetes Endocrinol 2026;14(6):450–462. doi:10.1016/S2213-8587(25)00402-4, abstract.
- Novo Nordisk, "Novo Nordisk files for FDA approval of CagriSema…", company announcement, 18 December 2025 — novonordisk.com.
- Novo Nordisk A/S, Form 6-K, 23 February 2026 (REDEFINE 4 headline results) — sec.gov.
- ClinicalTrials.gov API v2, intervention "cagrilintide", queried 25 September 2026: 44 records; REDEFINE 3 NCT05669755; results-posted record NCT04982575.
- FDA, Drugs@FDA via openFDA: no record for cagrilintide (25 September 2026); SYMLIN (pramlintide) NDA 021332, original approval 2005-03-16, all products listed as discontinued.