CagriSema

CagriSema combines cagrilintide 2.4 mg with semaglutide 2.4 mg in one weekly injection. It produced large weight loss in REDEFINE-1, but it remains under FDA review and failed to match tirzepatide in a sponsor-reported head-to-head trial.

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.

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 source

FDA 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

Read the original source

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.

REDEFINE-1 week-68 treatment-policy mean weight change
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%

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 source

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.

REDEFINE-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 source

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.

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 source

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.

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 source

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 source

FDA 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

Read the original source

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 source

REDEFINE-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 source

Why 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.