Cagrilintide
Also known as AM833, NN9838, Cagri, CagriSema (with semaglutide)
Cagrilintide is a long-acting analogue of the hormone amylin that reduces appetite through a different pathway than GLP-1 drugs. Alone it produced about 11 percent weight loss in Phase 2; paired with semaglutide as CagriSema it reached about 20 percent in Phase 3.
Overview
Cagrilintide is a long-acting analogue of amylin, a hormone the pancreas releases alongside insulin after meals. Natural amylin lasts only minutes and clumps into fibrils, which is why the older amylin drug pramlintide had to be injected before every meal. Novo Nordisk modified the sequence for stability and attached a fatty acid chain so it binds albumin and lasts about a week. It is the first amylin drug that works with once-weekly dosing.
As a single agent, the 26-week Phase 2 trial showed a dose-dependent effect topping out at about 10.8 percent weight loss at 4.5 mg weekly, similar to liraglutide 3 mg in the same trial and clearly better than placebo. Its real purpose is combination. Paired with semaglutide 2.4 mg as CagriSema, the REDEFINE 1 Phase 3 trial reported about 20 percent mean weight loss at 68 weeks, more than either component alone, though short of the 25 percent Novo had projected.
The amylin pathway is attractive because it works through different brainstem circuits than GLP-1, and people who plateau on a GLP-1 drug sometimes respond to adding it. Nausea is still the main side effect, though some evidence suggests amylin analogues are gentler on the gut than GLP-1 agonists for the same effect. No product is approved yet, and grey-market cagrilintide is unverified material, often sold in the same catalogs as semaglutide for people trying to reproduce CagriSema at home.
How it works
Cagrilintide activates amylin receptors, which are calcitonin receptors paired with receptor activity-modifying proteins, and it also has activity at the plain calcitonin receptor. Signaling in the area postrema and other brainstem regions produces satiety, slows gastric emptying and suppresses post-meal glucagon release. Because these are different receptors and largely different neurons than GLP-1 targets, the two signals add rather than compete, which is the rationale for CagriSema. The fatty acid chain binds albumin so a single weekly dose maintains steady levels, and the sequence changes prevent the aggregation that makes native amylin impractical as a drug.
What the research shows
- human RCT4.5 mg weekly produced 10.8 percent weight loss at 26 weeks as monotherapy, versus 3 percent on placebo (Phase 2).
- human RCTCagriSema (2.4 mg of each) produced about 20 percent weight loss at 68 weeks in adults with obesity (REDEFINE 1).
- human RCTIn type 2 diabetes, CagriSema produced about 14 percent weight loss with HbA1c reductions over 68 weeks (REDEFINE 2).
- human pilotIn a 20-week Phase 1b, cagrilintide plus semaglutide gave about 17 percent loss versus 10 percent for semaglutide alone.
- human RCTWeight loss on cagrilintide alone was similar to liraglutide 3 mg daily, an approved GLP-1 drug, in the same trial.
Evidence labels: rodent and in vitro mean no human data for that finding. Human pilot means small, often uncontrolled. Human RCT means randomized and controlled. Clinical means an approved drug with regulatory data.
Dose calculator
U-100 insulin syringeUnits are a volume on the syringe, not an amount of peptide. Concentration changes every time you change the water volume. The standalone calculator explains the math.
Dosing and protocol
Phase 2 started at 0.3 mg weekly and stepped every 4 weeks through 0.6, 1.2, 2.4 and 4.5 mg. The CagriSema dose is 2.4 mg paired with 2.4 mg semaglutide, reached by escalating both together.
Ongoing. Weight regain after stopping should be assumed.
Same day each week. In CagriSema trials it is given alongside semaglutide on the same day.
| Vial | Suggested water | Concentration | Low dose draw |
|---|---|---|---|
| 5 mg | 1 mL | 5 mg/mL | 6 units |
| 10 mg | 2 mL | 5 mg/mL | 6 units |
Lyophilized: fridge 2-8C away from light, freezer for long-term. Reconstituted: fridge 2-8C, use within 4 weeks.
Cautions
- ▲Nausea, vomiting and reduced appetite to the point of under-eating are the main effects; escalate slowly, especially when combining with a GLP-1 drug.
- ▲Injection site reactions were common in trials, more so than with semaglutide.
- ▲Slowed gastric emptying stacks with GLP-1 drugs, so combined use can affect oral medication absorption and anesthesia.
- ▲Hypoglycemia risk if used with insulin or sulfonylureas.
- ▲No approved product; identity and purity of grey-market vials are unverified.
Commonly stacked with
Frequently asked
What is amylin and why does it matter for weight?
Amylin is a hormone released with insulin after eating. It tells the brainstem you are full, slows the stomach and blunts glucagon. It is a separate satiety signal from GLP-1, which is why adding it to a GLP-1 drug produces more weight loss than either alone.
Can I add cagrilintide to semaglutide I am already taking?
That is exactly what CagriSema is, and the trials escalated both drugs together to 2.4 mg each. People adding it to an existing GLP-1 regimen usually start at 0.3 to 0.6 mg weekly and step up slowly, watching for nausea and under-eating. There is no trial data on adding it to tirzepatide.
Does it work on its own?
Yes, but modestly. The Phase 2 monotherapy trial showed about 11 percent loss at 26 weeks at the top dose, roughly on par with liraglutide. That is respectable, but the combination is where the big numbers are.
Can I mix it in the same syringe as semaglutide?
In trials they are given from a dual-chamber pen as separate injections. Community users often draw both into one syringe, which is convenient but untested for stability. Separate injections are the safer default.
References
- Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. The Lancet, 2021
- Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a phase 1b trial. The Lancet, 2021
- Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). New England Journal of Medicine, 2025