CagriSema Guide

CagriSema is Novo Nordisk's fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg (development code NN9838) — two different satiety drugs in a single once-weekly injection. Semaglutide is the GLP-1 receptor agonist behind Ozempic and Wegovy. Cagrilintide is a long-acting analogue of amylin, the hormone the pancreas releases alongside insulin at every meal. The two hormones signal fullness through completely separate receptor systems — which is the whole point of the combination.

Each component was built for weekly dosing. Cagrilintide is a 37-amino-acid peptide with a fatty-acid side chain that binds albumin, giving it a half-life of 159–195 hours; semaglutide's half-life is about 165 hours. Neither drug competes for the other's receptor: cagrilintide activates the amylin receptors (AMY1R–AMY3R) and the calcitonin receptor — a profile classed as a DACRA — while semaglutide activates only the GLP-1 receptor. In the phase 3 program the pair was tested head-to-head against each of its own components, in the same trial, at the same doses — the cleanest possible test of whether the combination earns its place.

The centerpiece is REDEFINE 1: 3,417 adults with obesity, or overweight with a weight-related condition, and no diabetes — randomized to CagriSema, semaglutide alone, cagrilintide alone, or placebo for 68 weeks, with both drugs in the combination escalated to 2.4 mg. Published in The New England Journal of Medicine in 2025. Headline figures below count every participant randomized, whether or not they stayed on treatment (the treatment-policy estimand — the stricter, real-world number).

Among participants who stayed on treatment (the trial-product estimand), the combination reached −22.7% — with 60% losing at least a fifth of their body weight and 40.4% losing at least a quarter. 88% of participants who began the trial with prediabetes were back to normal blood sugar at week 68. In a body-composition subgroup scanned by DXA, roughly two-thirds of the weight lost was fat mass and one-third lean soft tissue.

REDEFINE 2 — the diabetes trial. 1,206 adults with obesity or overweight and type 2 diabetes (starting HbA1c 7–10%), CagriSema against placebo for 68 weeks, published alongside REDEFINE 1 in The New England Journal of Medicine. Weight loss runs lower in diabetes across this whole drug class — and the combination still separated clearly, with the strongest blood-sugar result in the program:

The combination was proven in stages. In the phase 1b study (The Lancet, 2021), cagrilintide 2.4 mg added to semaglutide produced −17.1% in just 20 weeks, against −9.8% for semaglutide with placebo. In the phase 2 diabetes study (The Lancet, 2023), the full-dose pair reached −15.6% at 32 weeks against −5.1% for semaglutide alone and −8.1% for cagrilintide alone, with HbA1c down 2.2 points. Each step up in trial size kept the same ordering: the pair first, then the components.

The 2026 readouts. In REIMAGINE 2 (type 2 diabetes, reported at the American Diabetes Association meeting in June 2026), full-dose CagriSema cut HbA1c by 1.91 points against 1.75 for semaglutide alone, with weight loss of −14.2% against −10.2%. In September 2026, Novo Nordisk reported REIMAGINE 5: even the low-dose 1.0 mg + 1.0 mg combination beat low-dose tirzepatide in diabetes — −12.4% against −9.1% for tirzepatide 5 mg at 60 weeks, with matching blood-sugar control — and REDEFINE 9, where the same 1.0/1.0 mg pairing reached −21.0% against −2.0% for placebo at 68 weeks. A post hoc analysis presented in October 2026 found women on CagriSema averaged −25.0% on the stayed-on-treatment basis. The one readout that went the other way — the full-dose head-to-head against tirzepatide — is covered in How It Compares.

In the REDEFINE trials, both components started at 0.25 mg and escalated together every 4 weeks, reaching the full 2.4 mg + 2.4 mg dose at week 17. The slow ladder is what keeps the gastrointestinal effects manageable — each step gives the gut four weeks to adjust before the next. Syringe units below are per component, for a 10 mg vial mixed with 2.0 mL BAC water (5 mg/mL); the same units apply to each of the two vials.

The trial protocols allowed a dose level to be held or stepped back whenever tolerability required it, and some participants were maintained below the top dose. The schedule serves the research, not the other way around.

CagriSema in the trials was a single fixed-dose injection. The research components are supplied as separate lyophilized vials — cagrilintide 10 mg and semaglutide 10 mg — so a research protocol reconstitutes each vial the same way and draws the matched dose of each. Both are reconstituted with Bacteriostatic Water (BAC) under standard sterile handling:

Working with a different vial size or water volume? Run the exact numbers through the Peptopia Reconstitution Calculator before drawing a dose.

The safety picture is dominated by the gastrointestinal effects both components share — each slows the stomach in its own way, so the combination runs higher than either drug alone. In REDEFINE 1:

The events are the familiar set — nausea, vomiting, diarrhea, constipation, abdominal pain — clustered during dose escalation, dose-dependent, and mostly mild to moderate and temporary. Only about 6% of participants on the combination stopped treatment over side effects. Cagrilintide's own signature is at the injection site: 16.9% on cagrilintide alone reported injection-site reactions (against 2.6% on semaglutide) — mostly bruising and redness, mild, and not dose-dependent. The pattern argues for the protocol the trials used: escalate slowly, and hold a step when the gut objects.

Every compound on this shelf works the appetite system from a different angle. CagriSema is the only entry that is two drugs by design — and the only one that covers the amylin pathway and the GLP-1 pathway at the same time.

The honest exception. In REDEFINE 4 (February 2026) — an open-label, 84-week head-to-head in 809 adults — full-dose CagriSema met tirzepatide 15 mg directly and did not reach its non-inferiority goal: −23.0% against −25.5% among those who stayed on treatment (−20.2% against −23.6% counting everyone). Tirzepatide keeps the raw-weight-loss crown for now. Novo Nordisk answered with a higher-dose CagriSema program. REDEFINE 4 was not part of the FDA filing, which rests on the placebo-controlled REDEFINE 1 and 2 — but any honest account of this combination includes the loss alongside the wins.

CagriSema is an investigational combination — not an approved medicine in any country. Its regulatory position is nonetheless the most advanced of any amylin-based therapy: on December 18, 2025, Novo Nordisk filed the combination with the FDA — the first once-weekly GLP-1 + amylin fixed-dose combination ever submitted for approval — on the strength of REDEFINE 1 and REDEFINE 2. The application also went to Health Canada in December 2025.

Novo Nordisk guides to an FDA decision in the fourth quarter of 2026 (restated October 20, 2026); no public target date has been posted, and as of this writing the decision is still pending. Of the two components, semaglutide is an approved medicine in its own right (Ozempic, Wegovy); cagrilintide is approved nowhere. The wider program continues in parallel — a higher-dose CagriSema study after REDEFINE 4, a cardiovascular outcomes trial, and the REIMAGINE diabetes series — so the evidence base behind the pairing keeps growing while the first decision is awaited.

• New England Journal of Medicine — Garvey WT, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1). 2025;393:635–647.
• New England Journal of Medicine — Davies MJ, et al. Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2). 2025;393:648–659.

• The Lancet — Enebo LB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial. 2021.
• The Lancet — Frias JP, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. 2023.

• Novo Nordisk — Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management. Press release, December 18, 2025.
• Novo Nordisk — CagriSema demonstrates superior weight loss in adults with obesity or overweight in the REDEFINE 1 trial. Press release, December 20, 2024.
• Novo Nordisk — CagriSema associated with 25% weight loss on average for women in a post hoc analysis of REDEFINE 1. Press release, October 2026.
• Novo Nordisk — REDEFINE 4 head-to-head results (GlobeNewswire, February 23, 2026) and REIMAGINE 5 / REDEFINE 9 topline results (press release, September 21, 2026). Listed unlinked — no stable public link verified at build time.