# Cagrilintide

Novo's weekly amylin analogue, the 'cagri' in CagriSema; a hard appetite brake, often with heavy fatigue.

- Page: https://peprank.xyz/peptides/cagrilintide
- Category: Metabolic & weight (Research peptide)
- Also known as: 'cagri' / 'cag'; AM833; CagriSema (cagrilintide + semaglutide)
- Routes: Injection
- Safety tier: Strict: Avoid · Balanced: Caution · Evidence only: Caution
- Risk axes (0 none to 3 severe): Seen harm 1, Mechanism 2, Data gap 1, Silent harm 3, Product 3
- Positive: 36% of 25 graded reports glowing or positive, shrunk toward the 49% all-report average by 8 reports' weight
- Rank: #60 of 61 research peptides
- Graded reports: 25 (Glowing 2, Positive 6, Mixed 4, Nothing 2, Negative 11)
- Evidence: Human RCTs — Phase 2 (n=706) and a phase 3 monotherapy arm (n=302); as CagriSema, phase 3 REDEFINE 1, 2 and 4 and an FDA filing with a decision expected in Q4 2026; a standalone phase 3 (RENEW 1) is running; approved nowhere
- Access: Grey market
- Onset: Appetite effect within a day or two of a dose for many users; others only feel it by week 2-3 at a steady dose.
- Lasts: Dosed once weekly; several users say suppression fades by day 4-6 and split the dose.
- Cost per month: ≈ €27–110 (researchers' estimate)
- Dose users report: 54–210 mcg/day (median 140 mcg, n=9)
- Updated: 2026-10-30

**Why Avoid under the strict bar:** Unapproved drug bought as grey-market vials and usually stacked on retatrutide or tirzepatide outside any trial: gallbladder disease and fast lean-mass loss, severe hypoglycaemia if combined with insulin (amylin class), days of not eating from dosing errors with home-reconstituted vials, and a pH-sensitive peptide sold in plain powder.

## What users report

Twenty-five first-hand reports, almost all with cagri added to retatrutide, tirzepatide or semaglutide. Eight are good (stalls broken, 'appetite crushed', one 50 lb further loss on semaglutide plus 0.25-0.5 mg) and two who took it alone lost weight at 0.2-1 mg. The dominant complaint, in about half the threads, is fatigue or lethargy, sometimes 'debilitating', followed by low mood or anhedonia and, at 0.5-2.5 mg first doses, days of being unable to eat or vomiting. Users converge on starting at 0.1-0.25 mg. Because nearly everyone stacks it, its own effect is hard to separate. Felt nothing: 2 of 25 reports felt little even at 2-3 mg a week; a few more say the effect faded within weeks and needed doses doubled or tripled..

**Effects:** strong appetite and food-noise suppression, often described as aversion to food; breaks weight-loss stalls on GLP-1 drugs; 6-11% weight loss alone in trials (26-68 weeks); no heart-rate rise (heart rate fell 3.3 bpm in REDEFINE 1)

**Downsides:** fatigue or lethargy, the commonest user complaint; low mood or anhedonia; unable to eat for days, nausea and vomiting when started above 0.25 mg; constipation and bloating; injection-site reactions (17% vs 3% on placebo in REDEFINE 1); tolerance within weeks for some

**Risks:** Gallbladder disorders: 2.3% vs 1.0% on placebo with cagrilintide alone, 4.1% with CagriSema (REDEFINE 1); Pancreatitis seen with CagriSema (0.2%), none with cagrilintide alone in REDEFINE 1; Severe hypoglycaemia with insulin or sulfonylureas: the amylin analogue pramlintide carries a boxed warning for this; Rapid loss including lean mass when stacked on GLP-1 drugs and eating drops to near zero; Calcitonin-receptor agonism: long-term calcitonin was restricted by the EMA in 2012 over a cancer signal (theoretical for cagrilintide); Grey-market product: Novo formulates it at about pH 4 because amylin analogues aggregate; vendor powder and GLP-1 blends are mixed in plain bacteriostatic water

**Caveat:** The human trials are solid but were run with Novo's buffered formulation, slow escalation to 2.4 mg and no other weight-loss drug; nearly every Reddit report is cagri stacked on a GLP-1 from unverified vials, so neither its benefits nor its fatigue can be attributed cleanly. Talk of amyloid fibrils forming in badly reconstituted vials is a theoretical worry with no human case reports.

**Typical use:** Trials: 0.3-4.5 mg once weekly, 2.4 mg as the CagriSema dose after slow escalation. Grey-market users: start 0.1-0.25 mg, usually 0.25-2 mg weekly alongside a GLP-1.

**Getting it:** Not approved anywhere. Sold as 5-10 mg research vials and as 'cagri/sema' and 'reta/cagri' blend vials; users argue over adding acetic acid to reach Novo's roughly pH 4. CagriSema awaits an FDA decision expected in Q4 2026.

**Stacked with:** retatrutide (The commonest pairing, added at 0.1-1 mg when retatrutide leaves hunger late in the week; most fatigue and can't-eat reports come from this stack.); tirzepatide or semaglutide (A home-made CagriSema; semaglutide plus cagrilintide is the pairing Novo actually tested.); mazdutide or survodutide (Occasionally combined to hit amylin, GLP-1 and glucagon receptors at once; never studied.)

## Risk profile

- **Seen harm 1/3:** No regulator label exists for cagrilintide alone and no published case reports. In REDEFINE 1 its 302-person arm had serious adverse events in 8.9% vs 6.1% on placebo and gallbladder disorders in 2.3% vs 1.0%, numerically higher but not a clear signal; pancreatitis appeared only with CagriSema (0.2%). Reddit adds anecdotal days of vomiting and not eating after dosing errors, none documented as hospitalisation.
- **Mechanism 2/3:** Credible pathways: gallbladder disease from slowed gastric emptying and rapid weight loss (seen at 2.3% vs 1.0%), severe hypoglycaemia when an amylin agonist is combined with insulin (pramlintide's boxed warning), and agonism of the calcitonin receptor, the target of salmon calcitonin, whose long-term use the EMA restricted in 2012 after pooled trials showed 0.7-2.4% more cancers. The cancer link is an association of uncertain causality, and REDEFINE 1 showed no malignancy excess with cagrilintide at 68 weeks (0.7% vs 0.6%), so this stays at 2.
- **Data gap 1/3:** Not approved anywhere, but controlled trials put about 1,000 people on cagrilintide alone (706 in phase 2, 302 in REDEFINE 1) and several thousand on CagriSema for up to 84 weeks. The data cover Novo's buffered formulation at trial doses, not grey-market powder stacked with retatrutide.
- **Silent harm 3/3:** Most harms are noticed (not eating, vomiting, fatigue, low mood) or build silently but show on imaging and labs (gallstones, lean-mass loss). The mechanism axis also names the calcitonin-receptor cancer association, and under the rubric a theoretical tumour pathway is a 3 whatever its probability; without that pathway this axis would be a 2.
- **Product 3/3:** What people buy is grey-market injectable powder, often as blends with semaglutide or retatrutide, reconstituted at home. Amylin analogues aggregate and Novo formulates cagrilintide at about pH 4, which vendor vials in plain bacteriostatic water do not reproduce; dosing errors (2.5 mg instead of 0.25 mg) recur in reports.
- **Never if:** Pregnancy, planned pregnancy or breastfeeding; Insulin or sulfonylurea users (severe hypoglycaemia, as with pramlintide); History of pancreatitis or gallbladder disease; Gastroparesis or other severe GI motility disorder; Current or past eating disorder (users describe days of not eating and food aversion); Personal or family history of medullary thyroid carcinoma or MEN 2 when taken as CagriSema or with semaglutide (semaglutide boxed warning); Under 18

## Top reports

- Glowing, metabolic: “For the first time in my life I’ve cut out sugar, nicotine, caffeine and even porn. Impulsivity is no longer a factor in my life.” — [r/Retatrutide](https://www.reddit.com/r/Retatrutide/comments/1qvgf0h/reta_cagrisema_freedom_from_addiction/)
- Glowing, metabolic, 0.25-0.5 mg/week: “I was on Sema and lost 55 lbs in a year but then stalled. I added on just another .25mg-.5mg of weekly cagri and lost another 50 lbs in 6 months for a total of 105 lbs.” — [r/GLP1ResearchTalk](https://www.reddit.com/r/GLP1ResearchTalk/comments/1sci8l8/cagrilintide_is_an_absolute_force_multiplier_for/oecp6um/)
- Positive, metabolic, 1 mg/week with 3 mg retatrutide: “3mg Reta/1mg Cagri has been better for hunger and overall results than 15 of the Terz was for me. And prob half the cost.” — [r/Retatrutide](https://www.reddit.com/r/Retatrutide/comments/1limnvb/thanks_to_all_you_cagri_people/mzgrn9z/)
- Positive, metabolic, 0.2-0.3 mg/week: “I started with 0.2mg (7 units) and felt full some normal sized meals, still hungry on the others for the first whole week. The second week I took 0.3mg (10units) and now I am feeling it!! I am eating less than half of what I was before.” — [r/Peptidesource](https://www.reddit.com/r/Peptidesource/comments/1pa1a2t/cagrilintide/)
- Positive, metabolic, 0.25 mg/week: “I use a 10mg vial and dose at 250mcg. Initially it didn’t do much. But by week 3, definitely helps me with cravings. I can still eat my protein etc., but I don’t think I’ll ever go up in dose from here.” — [r/Retatrutide](https://www.reddit.com/r/Retatrutide/comments/1tfy7v6/dude_cagri_is_no_joke/omdvj5d/)

## Studies

- [Lau et al. 2021: once-weekly cagrilintide for weight management, dose-finding phase 2 trial (Lancet)](https://pubmed.ncbi.nlm.nih.gov/34798060/) (rct, n=706, 2021): Over 26 weeks cagrilintide 0.3-4.5 mg cut weight 6.0-10.8% vs 3.0% on placebo, and 4.5 mg beat liraglutide 3.0 mg (10.8% vs 9.0%); GI events 41-63% vs 32%, mainly nausea.
- [Garvey et al. 2025: REDEFINE 1, coadministered cagrilintide and semaglutide in adults with overweight or obesity (NEJM)](https://pubmed.ncbi.nlm.nih.gov/40544433/) (rct, n=3417, 2025): At 68 weeks CagriSema 2.4/2.4 mg cut weight 20.4% vs 3.0% on placebo; the 302-person cagrilintide-alone arm had serious adverse events in 8.9% vs 6.1%, gallbladder disorders 2.3% vs 1.0% and injection-site reactions 16.9% vs 3.0%.
- [Novo Nordisk 2025: REDEFINE 1 sub-analysis of cagrilintide 2.4 mg monotherapy (EASD)](https://www.globenewswire.com/news-release/2025/09/16/3150597/0/en/novo-nordisk-presents-phase-3-data-for-next-generation-amylin-cagrilintide-leading-to-advancement-into-dedicated-clinical-programme.html) (rct, n=302, 2025): Cagrilintide alone lost 11.8% (12.5 kg) vs 2.3% on placebo over 68 weeks, mostly with transient mild-to-moderate GI effects; Novo moved it into its own phase 3 programme.
- [Davies et al. 2025: REDEFINE 2, cagrilintide-semaglutide in adults with obesity and type 2 diabetes (NEJM)](https://pubmed.ncbi.nlm.nih.gov/40544432/) (rct, n=1206, 2025): In type 2 diabetes CagriSema cut weight 13.7% vs 3.4% on placebo at 68 weeks.
- [Novo Nordisk 2026: REDEFINE 4 head-to-head with tirzepatide (Form 6-K)](https://www.sec.gov/Archives/edgar/data/353278/000117184326000996/f6k_022326.htm) (rct, n=809, 2026): In an open-label 84-week trial CagriSema reached about 23% weight loss but failed to show non-inferiority to tirzepatide 15 mg; reported by press release, not yet peer-reviewed.
- [Kruse et al. 2021: development of cagrilintide, a long-acting amylin analogue (J Med Chem)](https://pubmed.ncbi.nlm.nih.gov/34288673/) (in-vitro, 2021): Amylin has a high propensity to form amyloid fibrils; cagrilintide was lipidated and stabilised to make a once-weekly drug possible, which is why its formulation matters.

## Sources

- [Lau et al. 2021, cagrilintide phase 2 (Lancet)](https://doi.org/10.1016/S0140-6736(21)01751-7)
- [Garvey et al. 2025, REDEFINE 1 (NEJM)](https://doi.org/10.1056/NEJMoa2502081)
- [Novo Nordisk 6-K, 23 Feb 2026: REDEFINE 4 missed non-inferiority vs tirzepatide; CagriSema filed with FDA December 2025](https://www.sec.gov/Archives/edgar/data/353278/000117184326000996/f6k_022326.htm)
- [RENEW 1: phase 3 trial of cagrilintide alone (NCT07220642)](https://clinicaltrials.gov/study/NCT07220642)
- [SymlinPen (pramlintide) prescribing information, boxed warning for severe hypoglycaemia with insulin](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff)
- [EMA 2012: calcitonin long-term use limited over increased cancer risk](https://www.ema.europa.eu/en/news/european-medicines-agency-recommends-limiting-long-term-use-calcitonin-medicines)
- [FDA: concerns with unapproved GLP-1 drugs used for weight loss](https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss)
- [Mendias & Awan 2026 preprint: 6441 grey-market peptide samples, 41.6-71.1% failed quality criteria, 15% endotoxin](https://europepmc.org/article/PPR/PPR1182497)