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.
Reviewed by the amino101 editorial team. , first published .
Quick start
What people commonly do. Not a prescription.- Typical dose
- 0.3 mg (starting dose)
- How often
- once weekly
- Where
- Subcutaneous, abdomen or thigh, rotate sites; injection site reactions are common
- Timing
- same day each week, any time; alongside semaglutide on the same day if combining
- Effects timeline
- reduced hunger and smaller portions within 1 to 2 weeks, weight loss builds over 4 to 12 weeks, still trending down at 26 weeks in phase 2
- Storage
- fridge 2 to 8 C once mixed, use within 4 weeks
- Cycle length
- ongoing, stepped every 4 weeks through 0.6, 1.2, 2.4 and 4.5 mg
- Break between
- none planned; assume weight regain after stopping and taper down
0.3 mg is the phase 2 starting step. Maintenance arms ran 0.6 to 4.5 mg weekly on its own; the CagriSema dose is 2.4 mg paired with 2.4 mg semaglutide, reached by escalating both together.
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.
Where the research stands
Weight management combined with semaglutideStrong evidence
- Obesity without diabetes (CagriSema). REDEFINE 1 phase 3 RCT, about 20 percent mean loss at 68 weeks, more than either drug alone.
- Early combination signal. Phase 1b, 20 weeks, about 17 percent loss versus 10 percent on semaglutide alone.
Weight management on its ownModerate evidence
- Monotherapy in obesity. Phase 2 RCT, 10.8 percent loss at 4.5 mg over 26 weeks, on par with liraglutide 3 mg.
Type 2 diabetes with obesityModerate evidence
- CagriSema in diabetes. REDEFINE 2 phase 3 RCT, about 14 percent loss with HbA1c reductions over 68 weeks.
Breaking a GLP-1 plateauEmerging
- Adding amylin to an existing GLP-1 regimen. Mechanistically sound and common in community protocols, but only the phase 1b combination data supports it and that started both drugs together.
- 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.
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.
Levels over time
Modeled from the half-life. Illustrative, not measured.Dosing every 7 d with a half-life of 7.5 d means each dose lands on top of what is left from the last one. Levels climb to about 2.1 times a single dose before settling, roughly 30 d in.
The week-long half-life is what makes a once-weekly amylin drug possible, and it means each dose step keeps building for about a month, so escalating faster than every 4 weeks stacks nausea before the previous step has even settled.
Cagrilintide dosage and protocols
Not cycled. Phase 2 used 4-week steps from 0.3 mg up to 4.5 mg, and the CagriSema trials escalated cagrilintide and semaglutide in lockstep to 2.4 mg each over 16 weeks. People adding it to a GLP-1 they already take usually start at 0.3 to 0.6 mg and climb slowly, since the two satiety signals add up fast.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Weeks 1 to 4, tolerance | 0.3 mg | once weekly | Subcutaneous |
| Weeks 5 to 8 | 0.6 mg | once weekly | Subcutaneous |
| Weeks 9 to 12 | 1.2 mg | once weekly | Subcutaneous |
| Weeks 13 to 16, CagriSema level | 2.4 mg | once weekly | Subcutaneous |
| Week 17 onward, monotherapy top dose if needed | 4.5 mg | once weekly | Subcutaneous |
Food does not matter for the injection. When paired with semaglutide, trials gave both on the same day; separate injections are the safer default over drawing both into one syringe, since mixed stability is untested. Keep the weekday consistent, and hold a step longer if nausea or under-eating has not settled.
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.
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.
| 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 |
How to reconstitute Cagrilintide
- 1
Wash your hands and wipe the work surface. Swab both vial stoppers with alcohol and let them dry.
- 2
Pick the water volume with the calculator above and write it on the vial. The concentration means nothing without it.
- 3
Draw the bacteriostatic water into a mixing syringe.
- 4
Insert at an angle and let the water run down the inside wall. Never squirt it straight onto the powder.
- 5
Swirl gently or leave it to dissolve. Do not shake.
- 6
Label with the date and water volume. Store in the fridge at 2 to 8 C and use within about 4 weeks.
- 7
Unmixed vials keep for months in the fridge and longer in the freezer, sealed and out of light.
- Full walkthrough with syringe reading and site rotation: reconstitution guide.
- ✓White, fluffy cake
Lyophilized powder should look like a small white puck or fluffy cake at the bottom of the vial. That is a proper freeze-dry.
- ✓Clear after mixing
Once dissolved the solution should be water-clear with nothing floating in it.
- !Slight clumping
Small clumps that dissolve with gentle swirling are fine. Shipping compacts powder.
- ✕Collapsed or melted
Powder stuck to the sides, glassy, or shrunken means it got hot in transit. Contact the vendor.
- ✕Cloudy or particles
Persistent cloudiness or visible particles after mixing means degraded or contaminated product. Do not use it.
- Week 1 to 4
Meals feel smaller and snacking drops, some nausea, injection site redness is common. Small early loss.
- Week 4 to 12
Appetite suppression firms up as the dose climbs, loss of roughly 1 pound a week alone or more when combined with a GLP-1 drug.
- Month 3 to 6
Steady loss, GI effects settle; on CagriSema the combined effect is clearly larger than semaglutide alone.
- Month 6 to 18
Loss continues toward the 20 percent range in combination, with a plateau in the second year.
Interactions and stacking
Semaglutidesynergistic
This is CagriSema, the only combination with phase 3 evidence; amylin and GLP-1 satiety signals add rather than overlap.
Tirzepatidecompatible
Community extension of the CagriSema idea; plausible mechanism, zero trial data, so escalate slowly.
Retatrutidecaution
No data at all for this pairing and the combined GI load is heavy; under-eating and severe nausea are the practical risks.
Pramlintideavoid
Same receptor, so it duplicates the effect of cagrilintide with no upside.
Insulin and sulfonylureascaution
Amylin analogues suppress glucagon and slow glucose absorption, which raises hypoglycemia risk with these drugs.
Oral medications with a narrow margincaution
Slowed gastric emptying stacks with GLP-1 drugs and can change absorption of warfarin, levothyroxine and similar.
Safety
- ▲Nausea and vomiting, worst after each dose increase
- ▲Injection site redness, itching or lumps, more common than with semaglutide
- ▲Appetite reduced to the point of under-eating and low energy
- ▲Constipation
- ▲Headache and fatigue in the early weeks
- ▲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.
- ■You are struggling to eat enough to maintain protein intake and basic energy
- ■Vomiting prevents keeping fluids down for more than a day
- ■Severe or persistent abdominal pain
- ■Injection site reactions spread, blister or fail to settle within a week
- ■Signs of low blood sugar if combined with insulin or a sulfonylurea
Community poll
Self-reported by visitors. Not clinical evidence.Cagrilintide: 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