Key facts
- Class: long-acting amylin receptor agonist (amylin analog), also known as AM833 or NNC0174-0833
- Mechanism: activates amylin and calcitonin receptors in the hindbrain, a satiation pathway entirely separate from GLP-1
- Developer: Novo Nordisk; almost all late-stage work is on CagriSema, the fixed cagrilintide + semaglutide combination
- Route: subcutaneous injection, once weekly; CagriSema uses a dual-chamber pen
- Approval status: investigational. Not approved anywhere. FDA New Drug Application for CagriSema submitted December 2025, under review
- Evidence level: strong. Multiple randomized phase 3 trials in thousands of participants, published in the New England Journal of Medicine and The Lancet
- Most reported adverse effects: nausea, constipation, vomiting, diarrhea, reduced appetite, mostly mild to moderate and transient
What is cagrilintide?
Cagrilintide is a synthetic analog of amylin, a 37-amino-acid hormone that pancreatic beta cells release into the blood alongside insulin every time you eat.
Native human amylin is a difficult drug candidate. It aggregates into amyloid fibrils, and it clears from the circulation in minutes. Both problems have been solved before: pramlintide, an amylin analog approved by the FDA in 2005, borrowed proline substitutions from rodent amylin to block fibril formation, but it still had to be injected at every meal alongside insulin (PubMed 18561511).
Cagrilintide, developed by Novo Nordisk under the codes AM833 and NNC0174-0833, went further. The medicinal chemistry paper describing its design shows a backbone re-engineered for solubility and stability plus a lipid side chain that binds circulating albumin, which slows renal clearance enough to support once-weekly subcutaneous dosing (PubMed 34288673). That single change turned a mealtime diabetes adjunct into a weekly obesity candidate.
It is important to be precise about naming, because the two terms get used interchangeably online and they are not the same thing. Cagrilintide is the molecule. CagriSema is the investigational combination product: cagrilintide 2.4 mg and semaglutide 2.4 mg, delivered together once a week from a dual-chamber pen. Nearly every headline number you have seen attributed to "cagrilintide" is actually a CagriSema number.
How amylin signaling differs from GLP-1
This is the whole rationale for the combination, and it is worth getting right.
GLP-1 is an incretin. It is secreted from intestinal L-cells after a meal, potentiates glucose-dependent insulin release, suppresses glucagon, slows gastric emptying, and reduces appetite partly through hypothalamic and brainstem circuits. That is the pathway behind every GLP-1 receptor agonist on the market.
Amylin is not an incretin. It is co-secreted with insulin from the beta cell, and its dominant appetite effect runs through the area postrema, a circumventricular region of the hindbrain that sits outside the blood-brain barrier and is densely populated with amylin receptors. Those receptors are built from the calcitonin receptor complexed with receptor activity-modifying proteins, giving the AMY1 to AMY3 subtypes. Signals from the area postrema relay through the nucleus of the solitary tract and the parabrachial nucleus to hypothalamic feeding centers (PubMed 39426704).
Functionally, amylin acts as a satiation signal that limits meal size and appears to interact with leptin sensitivity, while GLP-1 does more of its work on glucose handling and gastric transit. Reviews of the long-acting amylin class argue that because the two receptor systems are separate, their effects on food intake should stack rather than overlap (PubMed 35066542, PubMed 41747885). A phase 1 study of the two peptides given together supported that idea and showed no pharmacokinetic interference between them (PubMed 33894838).
That hypothesis is now the most-tested proposition in obesity pharmacology, and REDEFINE 1 is where it was put to the test.
Does cagrilintide actually work for weight loss?
On its own, yes, but less than a GLP-1 agonist. In combination, yes, and substantially more.
The dose-finding phase 2 trial randomized 706 adults with overweight or obesity across 57 sites to weekly cagrilintide at 0.3 to 4.5 mg, daily liraglutide 3.0 mg, or placebo for 26 weeks. Mean weight reduction ranged from 6.0% to 10.8% across the cagrilintide doses, against 9.0% for liraglutide and 3.0% for placebo. The highest dose corresponded to 11.5 kg lost versus 9.6 kg on liraglutide (PubMed 34798060). For a first-in-class weekly amylin analog with a 26-week readout, that was a strong signal, and it was roughly competitive with the then-standard liraglutide comparator.
But 10.8% at 26 weeks was never going to displace semaglutide, which delivered 14.9% at 68 weeks in STEP 1 (PubMed 33567185). The commercial and scientific case for cagrilintide rested on what it added on top of a GLP-1, not on what it did alone.
REDEFINE 1: the phase 3 results in full
REDEFINE 1 enrolled 3,417 adults with obesity, or overweight plus at least one weight-related condition, and no type 2 diabetes. Participants were randomized to weekly CagriSema, cagrilintide 2.4 mg alone, semaglutide 2.4 mg alone, or placebo for 68 weeks, all alongside lifestyle intervention (PubMed 40544433).
Because the trial reported two estimands, the numbers you see quoted vary. The trial-product estimand models what happens if everyone stays on treatment; the treatment-policy estimand counts everyone regardless of whether they stopped. Both are legitimate, and the honest way to read the trial is to look at both.
| Arm | Weekly dose | Weight change (trial-product estimand) | Weight change (treatment-policy estimand) |
|---|---|---|---|
| CagriSema | Cagrilintide 2.4 mg + semaglutide 2.4 mg | −22.7% | −20.4% |
| Semaglutide alone | 2.4 mg | −16.1% | Not the primary comparison |
| Cagrilintide alone | 2.4 mg | −11.8% | Not the primary comparison |
| Placebo | — | −2.3% | −3.0% |
The threshold data are what make the trial notable. Under the trial-product estimand, 97.6% of the CagriSema group lost at least 5% of body weight, 60.2% lost at least 20%, 40.4% lost at least 25%, and 23.1% lost at least 30%. Among participants who entered with a BMI of 30 or above, 50.7% finished below that threshold, compared with 10.2% on placebo. Very few obesity pharmacotherapies have put a quarter of participants past 30% weight loss.
Secondary cardiometabolic endpoints moved in the expected direction. A prespecified analysis of REDEFINE 1 published in Hypertension reported meaningful reductions in systolic blood pressure with CagriSema relative to placebo (PubMed 41328546). Whether that translates into fewer cardiovascular events is the question REDEFINE 3, an event-driven outcomes trial in roughly 7,000 people with established cardiovascular disease, is designed to answer. It has not reported.
CagriSema in type 2 diabetes
REDEFINE 2 ran the combination in 1,206 adults with obesity and type 2 diabetes for 68 weeks. Mean weight change was −13.7% with CagriSema against −3.4% with placebo, a treatment difference of 10.4 percentage points. Glycemic results were strong: 73.5% of the CagriSema group reached an HbA1c of 6.5% or lower, versus 15.9% on placebo, starting from a mean baseline HbA1c of 8.0% and a mean diabetes duration of 8.5 years (PubMed 40544432/).
The blunted weight response in type 2 diabetes is not specific to this drug. It shows up consistently across the class, including with tirzepatide, and is one of the more reliable patterns in obesity trials.
Earlier phase 2 work in type 2 diabetes had already shown the combination outperforming semaglutide alone on both weight and glucose (PubMed 37364590). The separate REIMAGINE program is now testing CagriSema specifically as a diabetes therapy, including head-to-head against its own components and as an add-on to basal insulin (PubMed 42251859). A phase 3a trial in Japan and Taiwan, REDEFINE 5, reported results broadly consistent with the global program (PubMed 42009015).
Cagrilintide vs semaglutide, tirzepatide, and retatrutide
Cross-trial comparisons are unreliable, so start with the head-to-head data that exist.
Versus semaglutide. This one is settled inside a single trial. In REDEFINE 1, CagriSema produced 22.7% weight loss against 16.1% for semaglutide 2.4 mg alone. Adding cagrilintide added roughly six and a half percentage points. That is a real, randomized, within-trial advantage.
Versus tirzepatide. This one did not go Novo's way. REDEFINE 4 randomized 809 adults with obesity to CagriSema or tirzepatide 15 mg for 84 weeks. CagriSema produced about 23% mean weight loss against roughly 25.5% for tirzepatide under the all-adherent analysis, and 20.2% against 23.6% under the treatment-regimen analysis. The trial failed its primary endpoint of noninferiority. These results were company-reported and presented at conference; at the time of writing they were not yet indexed as a peer-reviewed publication on PubMed, so treat the exact figures as provisional. For context, tirzepatide beat semaglutide directly in SURMOUNT-5 (PubMed 40353578) after delivering up to 20.9% in SURMOUNT-1 (PubMed 35658024).
Versus retatrutide. No head-to-head trial exists. Retatrutide, a triple GIP/GLP-1/glucagon agonist, reported 24.2% mean weight loss at 48 weeks in its phase 2 trial, but that was a phase 2 population and a different duration, and phase 3 data are still accruing. Comparing a phase 2 number to a phase 3 number is exactly the kind of cross-trial error that makes online rankings of these drugs unreliable.
The practical takeaway: cagrilintide's contribution is additive and well documented, but the combination has not yet demonstrated superiority over the best approved dual agonist. If you are trying to orient yourself across the whole category, the overview of peptides studied for weight loss lays out where each mechanism sits.
Cagrilintide side effects reported in trials
Gastrointestinal effects dominate, which is unsurprising given that both amylin and GLP-1 slow gastric emptying and act on brainstem nausea circuitry.
In REDEFINE 1, 79.6% of the CagriSema group reported at least one gastrointestinal adverse event, against 39.9% on placebo. The breakdown: nausea in 55% versus 12.6%, constipation in 30.7% versus 11.6%, and vomiting in 26.1% versus 4.1%. The trial characterized most of these as transient and mild to moderate, concentrated during dose escalation. Discontinuation because of adverse events was 6% with CagriSema and 3.7% with placebo, which is a low attrition rate for a drug producing this magnitude of effect.
Cagrilintide monotherapy in the phase 2 trial was gentler: gastrointestinal events in 41% to 63% of participants across doses versus 32% on placebo, nausea in 20% to 47% versus 18%, and only 4% discontinuing for adverse events. The combination is clearly harder on the gut than the amylin analog alone.
Two caveats matter. First, semaglutide-containing products carry the class boxed warning about thyroid C-cell tumors observed in rodents, which applies to the semaglutide half of the combination. Second, because cagrilintide has never been marketed, there is no post-marketing surveillance data on it, and rare adverse events are typically the ones that trials of a few thousand people miss. Every safety statement above describes randomized trial populations, not the general public.
Is cagrilintide FDA approved?
No. Cagrilintide is not approved by the FDA, the EMA, or any other major regulator, either alone or in combination.
Novo Nordisk submitted a New Drug Application to the FDA on 18 December 2025 for once-weekly CagriSema at cagrilintide 2.4 mg plus semaglutide 2.4 mg, for weight reduction and long-term weight maintenance in adults with obesity, or overweight with at least one weight-related condition, used with a reduced-calorie diet and increased physical activity. The filing rests primarily on REDEFINE 1. Review was expected to run through 2026, and no approval decision had been issued when this page was last updated.
Note what the filing covers and what it does not. The submission is for the fixed combination. Cagrilintide alone is not being pursued as a standalone obesity product, despite having a dedicated monotherapy arm in REDEFINE 1. If CagriSema is approved, the amylin analog will reach patients only as half of a combination pen.
Cagrilintide sold as a "research chemical"
Because cagrilintide has generated headlines without being approved, vials labeled with its name circulate through grey-market channels aimed at consumers. This is a materially different situation from buying an approved prescription drug.
An unapproved investigational drug cannot legally be sold or marketed for human use in the United States. Material sold under "research use only" labeling sits outside the regulated pharmaceutical supply chain, which means no verified identity, no verified purity, no sterility assurance, no cold-chain accountability, and no manufacturer liability. Independent testing of grey-market peptides has repeatedly found products that are underdosed, mislabeled, or contaminated. The dose-escalation schedules used in the REDEFINE trials also exist for a reason, and they were run under clinical supervision with monitoring that does not exist outside a trial.
We cover the regulatory framework in more detail in are peptides legal. PepMate does not sell peptides, recommend suppliers, or help anyone obtain unapproved substances.
What is worth logging on a weekly injectable
If you are under a clinician's care on any weekly injectable metabolic therapy, whether that is an approved GLP-1 today or a combination product later, the record you keep is what makes your appointments useful.
The things that consistently matter: the date of each injection and whether it drifted, which site you used and how you are rotating them, what your clinician changed and when, and a timestamped note on any nausea, constipation, or appetite change so you can see whether it tracks with escalation steps or is unrelated. Weight trend, meals, steps, and sleep round out the picture. Memory reconstructs all of this badly, and it is exactly the information a prescriber asks for.
PepMate exists to hold that record. It does not decide anything for you. If you want the broader background on how to keep a usable log, see how to track peptides, and the peptide Q&A library covers the common questions in short form.
Frequently asked questions
Is cagrilintide FDA approved?
No. Cagrilintide is investigational and is not approved by the FDA or any other major regulator, either on its own or as part of CagriSema. Novo Nordisk submitted a New Drug Application for once-weekly CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg) to the FDA in December 2025, based largely on REDEFINE 1. A regulatory decision had not been issued as of this article's update date.
What is the difference between cagrilintide and CagriSema?
Cagrilintide is a single molecule, a long-acting amylin analog. CagriSema is the investigational fixed-ratio combination product that pairs cagrilintide 2.4 mg with semaglutide 2.4 mg in one weekly injection delivered from a dual-chamber pen. Almost all late-stage development has been of the combination, not cagrilintide alone, because the two hormones act through separate receptor systems.
How does cagrilintide compare with semaglutide alone?
REDEFINE 1 compared them head to head over 68 weeks. Under the trial-product estimand, mean weight change was 22.7% with CagriSema, 16.1% with semaglutide 2.4 mg alone, 11.8% with cagrilintide 2.4 mg alone, and 2.3% with placebo. The combination beat either single agent, and cagrilintide monotherapy produced less weight loss than semaglutide monotherapy.
Is cagrilintide better than tirzepatide?
Not on the evidence so far. REDEFINE 4 randomized 809 adults with obesity to CagriSema or tirzepatide 15 mg for 84 weeks. CagriSema produced roughly 23% mean weight loss versus about 25.5% for tirzepatide and did not meet its primary endpoint of noninferiority. Those results were company-reported and presented at conference rather than indexed on PubMed at the time of writing.
What are the most common cagrilintide side effects?
Gastrointestinal effects dominate. In REDEFINE 1, 79.6% of the CagriSema group reported a gastrointestinal adverse event versus 39.9% on placebo, including nausea in 55%, constipation in 30.7%, and vomiting in 26.1%. Most events were mild to moderate and transient. Discontinuation for adverse events was 6% with CagriSema and 3.7% with placebo.
Can you take cagrilintide by itself?
Cagrilintide monotherapy has been studied in trials, including a 26-week phase 2 dose-finding study and the monotherapy arm of REDEFINE 1, but it is not being submitted for approval on its own. Novo Nordisk's regulatory filing covers the fixed-ratio CagriSema combination. There is currently no lawful route to a prescription for cagrilintide alone in the United States.
Is cagrilintide the same as pramlintide?
No, though both are amylin analogs. Pramlintide has been FDA approved since 2005 as a mealtime injection used alongside insulin in type 1 and type 2 diabetes, and it is dosed several times a day. Cagrilintide was engineered with a lipid side chain that binds albumin, extending its half-life enough for once-weekly dosing, and it targets obesity rather than mealtime glucose control.
How long does cagrilintide take to work?
In trials, weight curves separate from placebo within the first weeks of dose escalation, but the registrational endpoints are read at 68 weeks in REDEFINE 1 and REDEFINE 2 and at 84 weeks in REDEFINE 4. Weight loss with amylin-GLP-1 combinations was still trending downward late in the 68-week window rather than plateauing early.
Is cagrilintide legal to buy online?
Cagrilintide is an unapproved investigational drug, so it cannot be legally sold or marketed for human use in the United States. Vials advertised online as research chemicals are outside the regulated supply chain, carry no guarantee of identity, purity, or sterility, and are not manufactured under pharmaceutical quality standards. PepMate does not endorse or facilitate obtaining unapproved substances.
Sources
Every claim above traces to peer-reviewed literature indexed on PubMed:
- Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity — PubMed 40544433 (REDEFINE 1, NEJM 2025)
- Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes — PubMed 40544432 (REDEFINE 2, NEJM 2025)
- Once-weekly cagrilintide for weight management in people with overweight and obesity: a dose-finding phase 2 trial — PubMed 34798060 (Lancet 2021)
- Development of Cagrilintide, a Long-Acting Amylin Analogue — PubMed 34288673 (J Med Chem 2021)
- Safety, tolerability, pharmacokinetics and pharmacodynamics of concomitant administration of cagrilintide and semaglutide — PubMed 33894838 (Lancet 2021)
- Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes — PubMed 37364590 (Lancet 2023)
- Co-administered cagrilintide and semaglutide versus semaglutide alone in Japan and Taiwan (REDEFINE 5) — PubMed 42009015 (Lancet Diabetes Endocrinol 2026)
- Cagrilintide-semaglutide versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2) — PubMed 42251859 (Lancet Diabetes Endocrinol 2026)
- CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1 — PubMed 41328546 (Hypertension 2026)
- Long-acting amylin analogues for the management of obesity — PubMed 35066542 (Curr Opin Endocrinol Diabetes Obes 2022)
- Long-acting amylin-related peptides as therapies for obesity and type 2 diabetes — PubMed 41747885 (Peptides 2026)
- Central nervous system pathways targeted by amylin in the regulation of food intake — PubMed 39426704 (Biochimie 2025)
- Pramlintide, the synthetic analogue of amylin: physiology, pathophysiology, and effects on glycemic control, body weight, and selected biomarkers of vascular risk — PubMed 18561511
- Once-Weekly Semaglutide in Adults with Overweight or Obesity — PubMed 33567185 (STEP 1, NEJM 2021)
- Tirzepatide Once Weekly for the Treatment of Obesity — PubMed 35658024 (SURMOUNT-1, NEJM 2022)
- Tirzepatide as Compared with Semaglutide for the Treatment of Obesity — PubMed 40353578 (SURMOUNT-5, NEJM 2025)
REDEFINE 3 (cardiovascular outcomes) and REDEFINE 4 (versus tirzepatide) are referenced above from company disclosures and conference presentations. They were not indexed as peer-reviewed publications on PubMed at the time of writing, and this page will be updated when they are.