What CagriSema is
CagriSema is Novo Nordisk's fixed-dose combination of two once-weekly peptides: cagrilintide 2.4 mg, a lipidated analogue of the pancreatic hormone amylin, and semaglutide 2.4 mg, the GLP-1 receptor agonist in Wegovy. The two are co-administered from one pen. The name is simply the two components run together. As of September 2026 it is investigational: the phase 3 REDEFINE programme has reported, and Novo Nordisk has said regulatory submissions would follow, but no marketing authorisation had been granted.
Why amylin plus GLP-1
GLP-1 and amylin both reduce appetite, but through different receptors and partly different neural circuits. GLP-1 acts on the GLP-1 receptor in the hypothalamus, hindbrain and vagal afferents and slows gastric emptying. Amylin acts on calcitonin-receptor/RAMP complexes in the area postrema, a brainstem region outside the blood–brain barrier, and also slows gastric emptying and suppresses glucagon. Because the pathways are separate, their effects on intake are expected to add rather than overlap — and because amylin agonism at effective doses produces less nausea than GLP-1 agonism, the combination can reach higher total appetite suppression at a tolerable side-effect burden.
| Cagrilintide | Semaglutide | |
|---|---|---|
| Parent hormone | Amylin (37 aa) | GLP-1 (31 aa) |
| Receptors | Amylin (AMY1–3) + calcitonin | GLP-1R |
| Half-life | ≈ 7–8 days | ≈ 7 days |
| Lipidation | C20 diacid on N-terminal Lys | C18 diacid on Lys26 |
| Status alone | Investigational | Approved (Wegovy, Ozempic) |
Phase 1b: the pharmacokinetics work
The first question for any co-administered pair is whether the two drugs interfere with each other. The phase 1b study (Enebo et al., Lancet 2021; 96 participants) escalated cagrilintide from 0.16 to 4.5 mg alongside semaglutide 2.4 mg over 20 weeks and found that exposure to each was unaffected by the other: cagrilintide's half-life was 159–195 hours and semaglutide's 145–165 hours, matched well enough for a single weekly schedule. At 20 weeks, weight reductions of 15.7% and 17.1% were already seen with cagrilintide 1.2 and 2.4 mg plus semaglutide, versus about 9.8% with semaglutide plus placebo.
REDEFINE 1: the phase 3 obesity trial
REDEFINE 1 (Garvey et al., NEJM 2025) randomised 3,417 adults with overweight or obesity, without diabetes, to CagriSema, semaglutide alone, cagrilintide alone or placebo for 68 weeks. Mean weight change with CagriSema was −20.4% versus −3.0% with placebo, a difference of 17.3 percentage points; each monotherapy produced smaller reductions than the combination. Participants on CagriSema were more likely to reach every threshold from 5% to 30% weight loss. Gastrointestinal adverse events occurred in 79.6% versus 39.9% on placebo, mainly transient and mild to moderate. The result was below the roughly 25% some analysts had expected, in part because a proportion of participants did not reach the full dose, which shaped the design of later trials.
| Arm | Participants | Weight change |
|---|---|---|
| CagriSema 2.4/2.4 mg | 2,108 | −20.4% |
| Placebo | 705 | −3.0% |
| Semaglutide 2.4 mg alone | 302 | Smaller than combination |
| Cagrilintide 2.4 mg alone | 302 | Smaller than combination |
REDEFINE 2 and beyond
REDEFINE 2 tested CagriSema in adults with obesity and type 2 diabetes, where weight loss with incretin drugs is typically smaller; its results were published in 2026 in The Lancet Diabetes & Endocrinology. Further trials in the programme compare CagriSema with tirzepatide head-to-head and examine cardiovascular outcomes. Novo Nordisk's follow-on molecule, amycretin, delivers the same two mechanisms from a single peptide and has an oral formulation in development.
CagriSema vs tirzepatide vs retatrutide
Cross-trial percentages: CagriSema −20.4% at 68 weeks (REDEFINE 1); tirzepatide 15 mg −20.9% at 72 weeks (SURMOUNT-1); retatrutide 12 mg −24.2% at 48 weeks (phase 2). The three studies differ in population, duration and design, and only the CagriSema–tirzepatide comparison is being tested directly. Mechanistically, CagriSema is the only one of the three that uses amylin rather than GIP or glucagon as its second axis, which gives it a different side-effect logic — amylin agonism does not raise heart rate the way glucagon agonism does.
Approval status and availability
Neither CagriSema nor cagrilintide alone is approved anywhere as of September 2026. Semaglutide is approved, but CagriSema is a distinct product requiring its own authorisation. Nothing sold online as “CagriSema” or “cagrilintide” corresponds to a licensed product, and independent testing of such material cannot verify the lipidation, disulfide integrity or sterility that a pharmaceutical batch record would. This guide is educational and is not medical advice.
Sources and what they cover
These primary studies, official records and standards cover the topics linked below. The scope notes distinguish laboratory findings, human trials and regulatory records. This is a selected bibliography, not a systematic review or verification of every sentence; absence of a study here does not prove that no study exists.
- Enebo et al. (2021) — Cagrilintide with semaglutide, phase 1b
Early coadministration study; pharmacokinetics and tolerability do not prove long-term outcomes.
Relevant sections: Why amylin plus GLP-1 · Phase 1b: the pharmacokinetics work
- Garvey et al. (2025) — REDEFINE 1, cagrilintide with semaglutide
Randomized phase 3 obesity trial of the coadministered combination; not evidence for informal mixed research vials.
Relevant sections: What CagriSema is · REDEFINE 1: the phase 3 obesity trial
- Jastreboff et al. (2022) — SURMOUNT-1: tirzepatide for obesity
Randomized obesity trial; not a direct comparison with retatrutide.
Relevant sections: CagriSema vs tirzepatide vs retatrutide
- Jastreboff et al. (2023) — Retatrutide for obesity, phase 2 trial
Phase 2 obesity trial: studied regimens, weight and adverse events. Trial doses are not instructions for personal use.
Relevant sections: CagriSema vs tirzepatide vs retatrutide
FAQ
What is CagriSema?+
A once-weekly combination of cagrilintide 2.4 mg (an amylin analogue) and semaglutide 2.4 mg (a GLP-1 agonist) from Novo Nordisk. In the phase 3 REDEFINE 1 trial it produced −20.4% body weight at 68 weeks versus −3.0% with placebo.
Is CagriSema approved?+
No. As of September 2026 it is investigational; Novo Nordisk has said regulatory submissions would follow the REDEFINE programme.
How does CagriSema compare with tirzepatide?+
Cross-trial: −20.4% at 68 weeks (REDEFINE 1) versus −20.9% at 72 weeks (SURMOUNT-1 15 mg). A direct head-to-head trial is part of the REDEFINE programme.
Why combine cagrilintide with semaglutide?+
Amylin and GLP-1 reduce appetite through separate receptors and brain circuits, so their effects add. In REDEFINE 1 the combination outperformed either component alone.
What is the difference between CagriSema and amycretin?+
CagriSema is two peptides co-formulated; amycretin is one engineered peptide that activates both GLP-1 and amylin receptors, and it also has an oral formulation in trials.