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Cagrilintide (AM833)
An investigational once-weekly injectable long-acting amylin analogue developed for weight management. Honest framing: in a 26-week phase-2 dose-finding trial it produced ~6-11% mean weight loss as monotherapy (top dose modestly beating liraglutide 3 mg), and combined with semaglutide ("CagriSema") it drove larger weight loss in early trials. BUT cagrilintide is NOT APPROVED as a standalone drug. Cagrilintide has been studied alone in earlier trials and in a monotherapy arm of the phase 3 REDEFINE 1 trial. Results for cagrilintide plus semaglutide must not be attributed to cagrilintide alone. It is a prescription-pathway drug, not a dietary supplement, and grey-market versions are especially risky. Note the CagriSema combination is a separate product on its own development track.
Prescription medication — not a dietary supplement
Cagrilintide is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Cagrilintide doesn't have enough studies with structured effect-size data yet to pool a verdict. Browse the studies below for individual findings.
Most evidence is from high-quality meta-analyses and randomised trials published 2021–2026 with a typical study size of 1,206 participants.
Based on 30 studies · 4 meta-analyses · 10 RCTs · 44,486 total participants
Confidence
High confidenceBy outcome
An investigational drug with promising phase-2 monotherapy weight-loss RCTs and supportive meta-analyses, but no long-term or hard-outcome data, keeping confidence moderate.
17 randomised trials
76% were about Cagrilintide in an audit of 17 of them
Every randomised or controlled trial of Cagrilintide indexed in PubMed, not a hand-picked subset. Meta-analyses and systematic reviews are deliberately excluded from this count: most of them cover many compounds at once, so counting them would inflate it.
PubMed · as of Sep 2026
18 trials ongoing or recruiting · 24 completed on ClinicalTrials.gov
1 of the completed trials have posted results
Registered trials show research momentum for Cagrilintide, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Nov 2026
Cagrilintide (developmental code AM833) is a synthetic, lipidated long-acting analogue of amylin — the pancreatic hormone co-secreted with insulin from beta cells that signals satiety, slows gastric emptying, and reduces food intake.
Native amylin aggregates rapidly into amyloid fibrils and has a very short half-life (the marketed analogue pramlintide needs three injections daily), so cagrilintide was engineered for stability and protraction, giving a half-life of roughly 7-8 days suitable for once-weekly subcutaneous dosing.
It acts as an agonist at amylin and calcitonin receptors, engaging both homeostatic and hedonic appetite circuits in the brain. The human evidence is promising but still early.
The headline monotherapy result is a 26-week, multicentre, randomised, double-blind, placebo- and active-controlled phase-2 dose-finding trial (Lancet 2021, n=706 on cagrilintide) in people with overweight/obesity without diabetes: mean weight loss ranged ~6.0-10.8% across the 0.3-4.5 mg doses versus 3.0% on placebo, and the 4.5 mg dose modestly outperformed liraglutide 3.0 mg (10.8% vs 9.0%).
A phase-1b trial (Lancet 2021) co-administered ascending cagrilintide doses with semaglutide 2.4 mg and reported ~15-17% weight loss at 20 weeks with an acceptable safety profile — the proof of concept for the CagriSema combination.
A phase-2 trial in type 2 diabetes (Lancet 2023) compared CagriSema, semaglutide, and cagrilintide alone over 32 weeks; CagriSema gave the largest weight loss (~15.6%), while cagrilintide alone gave ~8.1%.
Meta-analyses pool these early trials and consistently find CagriSema beats semaglutide on weight loss, with cagrilintide monotherapy roughly comparable to semaglutide/liraglutide but with less vomiting.
The CagriSema combination has since advanced to large phase-3 trials (REDEFINE program, NEJM 2025): REDEFINE-1 (n=3,417, no diabetes) reported ~20.4% weight loss at 68 weeks vs 3.0% on placebo and included a small cagrilintide-monotherapy arm, and REDEFINE-2 (n=1,206, type 2 diabetes) reported ~13.7% vs 3.4%.
The honest caveats remain substantial. Cagrilintide has been studied alone in earlier trials and in a monotherapy arm of the phase 3 REDEFINE 1 trial. Results for cagrilintide plus semaglutide must not be attributed to cagrilintide alone. There is no cardiovascular, renal, or mortality outcome data for it alone.
Cagrilintide is INVESTIGATIONAL — it is not a dietary supplement. Adverse effects are class-typical amylin/GLP-1-style gastrointestinal events (nausea, constipation, diarrhoea) plus injection-site reactions; a dedicated thorough-QT study found no clinically relevant QTc prolongation.
The CagriSema combination is being developed separately and is on its own (largely phase-3) track, so its results should not be read as evidence for cagrilintide monotherapy.
Crucially, unregulated 'cagrilintide' is being sold grey-market online; using an investigational peptide with no clinical oversight, no identity/purity guarantee, and no safety monitoring is especially dangerous.
Because it is a prescription-pathway investigational drug rather than a supplement to recommend, it is sandboxed out of goal-based and stack recommendations here.
Cagrilintide is a long-acting analogue of the pancreatic hormone amylin, engineered for stability against amyloid aggregation and a ~7-8 day half-life. It agonises amylin and calcitonin receptors, the same axis exploited by the short-acting analogue pramlintide — but once-weekly rather than thrice-daily.
Amylin signalling induces satiety via both homeostatic and hedonic appetite circuits in the brain, slows gastric emptying, and reduces food intake. This is the mechanistic basis for cagrilintide's weight-loss effect and is complementary to (not the same as) the GLP-1 pathway hit by semaglutide.
Because amylin and GLP-1 reduce appetite through separate-but-related mechanisms, combining cagrilintide with semaglutide (the CagriSema combination) appears to have an additive effect on appetite and weight loss in early trials. This rationale underpins a separate combination-product development program, distinct from cagrilintide monotherapy.
How Cagrilintide works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
There is no approved standalone use; obtaining or using grey-market 'cagrilintide' means taking an unapproved investigational drug with no clinical oversight, dosing standard, or product-quality guarantee. Strongly discouraged.
Hypoglycemia risk if combined with glucose-lowering agents; only relevant under trial-level medical supervision with secretagogue adjustment.
Amylin/incretin-class caution applies; unsupervised use is particularly unwise without long-term safety data.
Contraindicated — not studied; weight-loss pharmacotherapy is avoided in pregnancy.
Amylin-class agonism slows gastric emptying, which can reduce the rate/extent of absorption of co-administered oral drugs — relevant for time-critical or narrow-therapeutic-index oral medicines.
Combining a glucose-lowering agent with insulin or sulfonylureas can increase hypoglycemia risk; dose adjustment of the secretagogue may be required in supervised use.
Cagrilintide is being studied combined with semaglutide (CagriSema) under trial supervision, where GI adverse events are additive. Combining amylin and GLP-1 agonists outside a supervised setting compounds gastrointestinal toxicity and is not appropriate for self-administration.
Tip: Dose-related; mitigated by a lower starting dose and slow escalation. Most cases mild-to-moderate. Notably lower vomiting than with semaglutide/liraglutide in pooled data.
Tip: Class-typical GI effects; generally transient and dose-related.
Tip: Rotate injection sites; usually mild and self-limiting.
Tip: Rapid weight loss is associated with gallbladder events; report severe abdominal pain. Long-term incidence not characterised.
Tip: Marked appetite suppression; as with weight-loss pharmacotherapy generally, some of the weight lost may be lean mass — adequate protein and resistance exercise are advised in supervised settings.
Cagrilintide has an evidence score of 5/10 — moderate evidence based on 30 indexed studies, including 2 meta-analyses. An investigational once-weekly injectable long-acting amylin analogue developed for weight management. Honest framing: in a 26-week phase-2 dose-finding trial it produced ~6-11% mean weight loss as monotherapy (top dose modestly beating liraglutide 3 mg), and combined with semaglutide ("CagriSema") it drove larger weight loss in early trials. BUT cagrilintide is NOT APPROVED as a standalone drug. Cagrilintide has been studied alone in earlier trials and in a monotherapy arm of the phase 3 REDEFINE 1 trial. Results for cagrilintide plus semaglutide must not be attributed to cagrilintide alone. It is a prescription-pathway drug, not a dietary supplement, and grey-market versions are especially risky. Note the CagriSema combination is a separate product on its own development track. Representative study: PMID 38286487.
Dosing for Cagrilintide: SupStack does not provide a self-directed dosing protocol for Cagrilintide. A dose used in a clinical trial does not establish a safe consumer dose. Phase-2 trials used once-weekly subcutaneous injection with stepwise escalation up to 4.5 mg maintenance.
Timing is flexible for Cagrilintide — consistent daily use matters more than the time of day. Trials dosed once weekly subcutaneously with gradual dose escalation over ~6 weeks to limit gastrointestinal effects; the ~7-8 day half-life supports once-weekly administration.
No consumer dose of Cagrilintide is endorsed, so there is no dose at which it can be called safe. Talk to a healthcare provider before taking it. Reported side effects include gallbladder / biliary events, decreased appetite / lean-mass loss, nausea. How often they occur is not established for all of them. Use caution if any of these apply to you: Not a dietary supplement and not an approved standalone drug — investigational; do not self-source grey-market vials; History of pancreatitis (amylin/incretin-class caution); Pregnancy and breastfeeding.
What side effects does Cagrilintide have?Don't take this if…
Semaglutide
Too few graded studiesAn FDA-approved GLP-1 receptor agonist (Ozempic/Rybelsus for type 2 diabetes, Wegovy for chronic weight management) with genuinely strong, large-RCT evidence for glycemic control and substantial weight loss, plus a cardiovascular-outcomes benefit. Honest appraisal: this is a real prescription medicine with real efficacy AND real risks — a US FDA boxed warning for thyroid C-cell tumors, pancreatitis and gallbladder risk, very common GI side effects, and growing concern about grey-market/compounded versions. It is a prescription drug, not a supplement, and is never auto-recommended.
Tirzepatide
Too few graded studiesAn FDA-approved prescription medication (Mounjaro for type 2 diabetes, Zepbound for obesity and obstructive sleep apnea), not a dietary supplement. Honest appraisal: in head-to-head phase-3 trials it is the most effective approved weight-loss drug to date — up to ~21% body-weight loss over 72 weeks and superior to semaglutide — but it is a real medicine with real risks: a US FDA boxed warning for thyroid C-cell tumors, common GI side effects, and pancreatitis/gallbladder signals. Do not source or use it outside a prescription.
Liraglutide
Too few graded studiesAn FDA-approved, once-daily GLP-1 receptor agonist (Victoza for type 2 diabetes, Saxenda for chronic weight management). Honest appraisal: a real prescription medicine with genuinely strong large-RCT evidence for glycemic control and moderate weight loss, plus a cardiovascular-outcomes benefit (LEADER). It also carries real risks — a US FDA boxed warning for thyroid C-cell tumors, pancreatitis and gallbladder risk, very common GI side effects, and lean-mass loss with weight loss. It is a prescription medicine, NOT a supplement, and is not auto-recommended.
Orforglipron
Too few graded studiesAn ORAL, non-peptide small-molecule GLP-1 receptor agonist for obesity, also studied in type 2 diabetes — the headline is the convenience of a once-daily pill (no injection, no cold chain, no food/water restrictions) delivering GLP-1-class glycemic and weight benefit. In the US, orforglipron is approved as Foundayo for long-term weight management in adults with obesity, or overweight with at least one weight-related condition, together with a reduced-calorie diet and increased physical activity. FDA approval was granted on 1 April 2026. An EMA list dated 5 October 2026 places orforglipron under evaluation. Honest appraisal: the phase-2 data are strong and the phase-3 read-outs (ATTAIN/ACHIEVE) are promising, but it has the full GLP-1-class side-effect burden (very common dose-dependent nausea/vomiting/diarrhea, higher discontinuation than injectables in some comparisons), the US label carries a boxed warning about thyroid C-cell tumours, and long-term outcomes are unsettled. It is NOT a dietary supplement.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 30 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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