CagriSema
updated
CagriSema is a fixed-dose combination of the amylin analog cagrilintide and the GLP-1 drug semaglutide in one weekly injection; Novo Nordisk filed it for US approval in December 2025. It is promoted as matching or beating tirzepatide. In REDEFINE-1, 3,417 adults without diabetes lost 20.4% of body weight at 68 weeks counting everyone who started, against 14.9% on semaglutide alone, but in REDEFINE-4 it missed noninferiority to tirzepatide, 23.0% against 25.5%, and gut side effects affected 79.6% against 39.9% on placebo. Graded B for large phase 3 weight loss while FDA review is pending.
Fixed-dose cagrilintide and semaglutide combination
- Fixed-dose amylin analog plus GLP-1 receptor agonist
- Investigational in the United States
- Directly compared with tirzepatide in REDEFINE-4
Is CagriSema approved or still under review?
Novo Nordisk says it submitted CagriSema for U.S. approval in December 2025. FDA Drugs@FDA and openFDA records contained no exact-name approval, so approval timing remains unknown.
The filed application has no final FDA decision or prescribing label. Approved indications, contraindications, and product claims remain undetermined.
source: CagriSema · December 2025 U.S. filing, Novo Nordisk, 2025 annual report
source: FDA records · CagriSema status, FDA Drugs@FDA and openFDA records
What did REDEFINE-1 show for the combination and each component?
At week 68 under the treatment-policy estimand, mean weight change was -20.4% with CagriSema, -11.5% with cagrilintide, -14.9% with semaglutide, and -3.0% with placebo. The trial randomized 3,417 adults without diabetes.
The trial's 22.7% CagriSema value comes from the adherence-assuming estimand; the treatment-policy estimate was 20.4%.
A larger effect than either component supports an added combination effect in this trial. It does not by itself identify a molecular synergy mechanism.
| Arm | Mean change |
|---|---|
| CagriSema 2.4/2.4 mg | -20.4% |
| Cagrilintide 2.4 mg | -11.5% |
| Semaglutide 2.4 mg | -14.9% |
| Placebo | -3.0% |
source: REDEFINE-1 · combination and component arms, Garvey et al., New England Journal of Medicine, 2025
Did CagriSema beat tirzepatide in REDEFINE-4?
In Novo Nordisk's 84-week open-label sponsor disclosure, CagriSema did not meet the primary noninferiority objective against tirzepatide 15 mg. Mean change was -20.2% versus -23.6% under the treatment-regimen estimand and -23.0% versus -25.5% under the efficacy estimand.
This is a direct comparison, but the cited evidence is a sponsor topline rather than a full peer-reviewed report.
source: REDEFINE-4 · tirzepatide comparison, Novo Nordisk, 2026
How common were adverse effects and discontinuation in REDEFINE-1?
Gastrointestinal events occurred in 79.6% of CagriSema participants versus 39.9% with placebo. Novo Nordisk reported adverse-event discontinuation of 5.9% versus 3.7%.
REDEFINE-1 measured both efficacy and adverse effects for the fixed-dose combination. Results from either component alone do not supply the combination's tolerability rate.
Does REDEFINE-1 establish durable weight loss after stopping CagriSema?
The main trial measured 68 weeks of assigned treatment and did not test how much weight is maintained after stopping CagriSema.
Studies and sources
CagriSema · December 2025 U.S. filing
Company annual report
Novo Nordisk, 2025 annual report
Novo Nordisk states that it filed CagriSema for its first U.S. regulatory approval in December 2025.
- Participants / model
- U.S. regulatory submission
- Treatment
- Cagrilintide 2.4 mg plus semaglutide 2.4 mg
- Follow-up
- Filed December 2025
- Study design
- Company regulatory disclosure
The cited filing predates an FDA decision and final label.
Read the original sourceFDA records · CagriSema status
Regulatory database record set
FDA Drugs@FDA and openFDA records
The cited U.S. approval records contain no exact-name CagriSema or cagrilintide-semaglutide entry.
- Participants / model
- United States drug approvals
- Treatment
- CagriSema and cagrilintide-semaglutide
- Study design
- Exact-name U.S. approval coverage
REDEFINE-1 · combination and component arms
Randomized trial
Garvey et al., New England Journal of Medicine, 2025
In 3,417 adults without diabetes, CagriSema produced -20.4% mean weight change versus -3.0% with placebo under the treatment-policy estimand; component arms lost less.
- Participants / model
- Adults with obesity or overweight plus a complication, without diabetes
- Treatment
- CagriSema, cagrilintide, semaglutide, or placebo weekly
- Follow-up
- 68 weeks
- Study design
- Randomized, double-blind, active- and placebo-controlled phase 3 trial
- Funding
- Novo Nordisk
The 22.7% estimate assumes adherence. The study did not report weight maintenance after treatment stopped.
Read the original sourceREDEFINE-4 · tirzepatide comparison
Sponsor phase 3 disclosure
Novo Nordisk, 2026
Novo Nordisk reported that CagriSema did not demonstrate noninferiority to tirzepatide, with smaller mean weight reductions under both estimands.
- Participants / model
- Adults with obesity
- Treatment
- CagriSema 2.4/2.4 mg or tirzepatide up to 15 mg
- Follow-up
- 84 weeks
- Study design
- Open-label randomized phase 3 trial
Topline sponsor disclosure awaits full peer-reviewed reporting.
Read the original sourceWhy is CagriSema in B tier?
B tier reflects large phase 3 weight-loss effects. CagriSema remains under FDA review, and its sponsor-reported REDEFINE-4 comparison did not meet the noninferiority objective against tirzepatide. The trials do not identify a molecular synergy mechanism.
read CagriSema in the reptides guide, chapter 47: 15 pages, free to read.
how tiers are graded: methodology · every cited source · about reptides.
Research reference, not medical advice. Entries distinguish product labels, study doses and reported protocols. Check the linked source for the product, route and population.