Cagrilintide vs Retatrutide: differences, evidence and safety
Answer first
Cagrilintide copies amylin, a hormone the pancreas releases with insulin, and is developed mainly as a partner to semaglutide. Retatrutide switches on the receptors for three hormones, GIP, GLP-1 and glucagon. Both are experimental and approved nowhere. No study comparing them directly could be found, so the figures below come from separate trials and cannot be ranked.
At a glance
How they work
Both substances are peptides made in the laboratory and studied for weight loss. They come from different companies and act on different hormone systems. Cagrilintide, a chain of 37 amino acid building blocks, comes from Novo Nordisk [1], [2]. Retatrutide, a chain of 39 amino acid building blocks, comes from Eli Lilly [3], [4].
Cagrilintide
- A copy of amylin. Amylin is a hormone that the pancreas releases together with insulin, and it helps signal that a meal is finished. The natural hormone disappears within minutes and clumps into fibres; cagrilintide was altered to avoid both [1].
- Two kinds of receptor. It switches on all three amylin receptors, named AMY1, AMY2 and AMY3, and also the calcitonin receptor directly. The literature therefore calls it a dual amylin and calcitonin receptor agonist (DACRA) [5], [6].
- Appetite. In animals it reduces how much is eaten. Mice lacking the relevant helper proteins responded far less, which points to the AMY1 and AMY3 receptors [7].
- An open question. A 2026 review asks whether the reduced eating reflects ordinary fullness or an unpleasant sensation; in humans this is unanswered [8].
Retatrutide
- Three receptors, GIP, GLP-1 and glucagon. In laboratory tests it is more active at the GIP receptor than at the other two [4].
- Stomach and appetite. Switching on the GLP-1 receptor makes people eat less. A dedicated early-stage study confirmed that the stomach empties more slowly [9].
- The glucagon part. The idea is that it raises the energy the body burns and changes how the liver handles fat [4]. A direct measurement of this in people could not be found in the sources reviewed.
The core difference is the hormone family. Retatrutide works through gut hormone receptors plus glucagon [4]. Cagrilintide works through amylin and calcitonin receptors instead [5]. Cagrilintide is mostly studied alongside semaglutide, a GLP-1 drug, as the fixed combination CagriSema [10].
Both carry a fatty acid chain that makes them cling to albumin, a carrier protein in the blood. The body takes roughly seven to eight days to clear half a dose of cagrilintide; the measured half-life was 159 to 195 hours [11]. For retatrutide it takes about six days [12].
What the studies show
No study that compares cagrilintide and retatrutide directly could be found in the published record reviewed for this page. Everything below comes from separate trials.
Those trials enrolled different people, gave different doses, measured different endpoints and ran for different lengths of time. Their numbers cannot be set against each other. Two further cautions apply. Most widely quoted cagrilintide figures belong to the combination with semaglutide, not to cagrilintide alone. And by 6 September 2026 no late-stage retatrutide trial had been published in full [13].
Weight in adults without diabetes
Phase 2 RCT The largest published trial of cagrilintide on its own enrolled 706 adults with overweight or obesity and without diabetes. After 26 weeks, weight had fallen by 6.0% to 10.8% across five doses, against 3.0% on a dummy injection (placebo) [14].
Phase 2 RCT In a mid-stage trial of retatrutide, 338 adults with obesity received one of four doses or a placebo for 48 weeks. Their weight fell by 8.7%, 17.1%, 22.8% and 24.2% from the lowest to the highest dose, against 2.1% on placebo [15].
Phase 3 (press release only) TRIUMPH-1 followed 2,339 adults without diabetes for 80 weeks. The manufacturer reported losses of 19.0%, 25.9% and 28.3% across three retatrutide doses, against 2.2% on placebo. These figures come from the manufacturer's press release; a peer-reviewed report could not be found [16].
The two mid-stage trials differ in length, 26 against 48 weeks, so even their headline figures describe different stretches of treatment.
Meta-analysis A 2026 analysis pooled four trials with 5,023 participants. Cagrilintide on its own reduced weight by 6.08% more than placebo [17]. All the pooled trials were run by the same company.
Weight with the combination partner
These results belong to cagrilintide plus semaglutide, not to cagrilintide alone.
Phase 3 RCT, combination REDEFINE 1 gave the combination to 3,417 adults with obesity and without diabetes for 68 weeks. Weight fell by 20.4%, against 3.0% on placebo [18]. The trial also ran a cagrilintide-only arm, but the published report gives no separate figure for it.
Phase 3 RCT, combination REDEFINE 2 repeated the design in 1,206 adults who also had type 2 diabetes. Weight fell by 13.7%, against 3.4% on placebo [19].
A comparable combination trial for retatrutide could not be found in the sources reviewed; it is studied as a single substance.
Long-term blood sugar in type 2 diabetes
Both were tested on glycated haemoglobin, a blood value that reflects average blood sugar over the past two to three months.
Phase 2 RCT A trial in 92 adults with type 2 diabetes ran for 32 weeks. The value fell by 0.9 percentage points on cagrilintide alone, 1.8 on semaglutide alone and 2.2 on the combination [20]. The 2026 meta-analysis found no reliable effect of cagrilintide alone on this value [17].
Phase 2 RCT A mid-stage trial tested retatrutide in 281 adults with type 2 diabetes. After 24 weeks the value fell by 0.43 points on the lowest dose and 2.02 points on the highest. On placebo it barely moved, at 0.01 points, and on the established drug dulaglutide it fell by 1.41 points [21].
Phase 3 (press release only) TRIUMPH-2 followed 1,152 adults with type 2 diabetes for 80 weeks. Weight fell by 12.7%, 19.1% and 20.8% across three retatrutide doses, against 4.0% on placebo. Long-term blood sugar fell by 1.4 to 1.6 points from a starting value of 7.7% [22].
Heart
Phase 3 (press release only) TRIUMPH-3 enrolled 1,949 adults with severe obesity and diagnosed heart disease. Counted broadly, serious heart events gave a hazard ratio of 0.82, with a range of 0.55 to 1.22. Counted narrowly, the hazard ratio was 1.12, with a range of 0.64 to 1.96 [22]. Both ranges include no difference, so they show neither a benefit nor a harm.
Phase 1, dedicated study For cagrilintide, a study in healthy volunteers looked for effects on the heart's electrical recovery. It found none of clinical importance at the highest dose tested [23].
A completed outcome trial could not be found for either substance. REDEFINE 3, a trial of the cagrilintide combination, is counting heart attacks and strokes in 7,101 people. It is not due to finish before October 2027 [24]. TRIUMPH-Outcomes, a trial of retatrutide, enrols 10,000 people and will not reach its main result before February 2029 [25].
Outcomes studied for only one of the two
- Retatrutide and liver fat. A sub-study enrolled 98 people without diabetes whose livers were at least 10% fat. After 24 weeks scans showed the fat content down by 42.9%, 57.0%, 81.4% and 82.4% across four doses, against a rise of 0.3% on placebo [26].
- The cagrilintide combination and blood pressure. In REDEFINE 1, upper blood pressure fell by 10.9 mmHg on the combination against 2.8 mmHg on placebo [27].
- Retatrutide and knee pain (press release only). TRIUMPH-4 enrolled 445 adults with worn knee joints. Over 68 weeks their pain score fell by 4.5 and 4.4 points from 6.0, against 2.4 points on placebo [28].
Safety
Both safety records come only from trials run by the manufacturers. Because neither substance is approved, there is no approved product information and no official weighing of benefits against risks. Retatrutide's late-stage figures come only from press releases. The lists below are therefore not a ranking.
Cagrilintide. The figures come from the mid-stage trial of cagrilintide alone unless the combination is named [14].
- Stomach and bowel. These complaints affected 41% to 63% of participants on cagrilintide, against 32% on placebo. Nausea alone ran at 20% to 47%, against 18% [14].
- With the combination. In REDEFINE 1 stomach and bowel complaints affected 79.6% on the combination, against 39.9% on placebo [18].
- Needle-site reactions. Reactions where the needle goes in were the second most common group [14].
- Stopping treatment. About 10% stopped in the mid-stage trial, 4% of them because of side effects [14].
- Serious events in pooled data. One analysis pooled three trials. It found serious side effects roughly 1.8 times as often on cagrilintide alone as on semaglutide (risk ratio 1.83) [29].
- Open questions. The calcitonin receptor is active in bone, and a study of bone turnover was still running in 2026 [24]. Long-term human data showing that the engineered-out clumping stays out could not be found [1], [30].
Retatrutide. The figures compare the highest dose with placebo in TRIUMPH-1 and come from a press release only [16].
- Stomach and bowel. Nausea affected 42.4% against 14.8%, diarrhoea 32.0% against 13.5%, constipation 26.1% against 10.9% and vomiting 25.3% against 4.8% [16].
- Odd skin sensations. Tingling, burning or numbness (dysesthesia) affected 12.5% against 0.9% [16].
- Stopping treatment. Across the three doses 4.1%, 6.9% and 11.3% stopped, against 4.9% on placebo [16].
- A faster pulse. In the mid-stage trial the heart rate rose with the dose and peaked at week 24 [15]. One independent assessment puts the largest rise at 6.7 beats per minute; another flags mild to moderate irregular heartbeat [31], [32].
A 2026 case report describes a man with type 1 diabetes who injected a product sold online under the retatrutide name. He developed severe vomiting, a dangerous build-up of acids in the blood and sudden kidney damage [33]. The authors point out that the product's contents had not been verified.
Data on pregnancy, breastfeeding and children could not be found for cagrilintide; its trial in children and adolescents is due to finish in 2033 [24]. For retatrutide, fully published late-stage safety tables could not be found [13].
Why this page lists no doses. Both substances are experimental drugs, approved nowhere and given only inside supervised trials. Any amount would describe trial conditions, not something to follow. This page therefore names doses only by their rank among those tested, never as an amount.
Legal status
Neither substance is approved in any of the seven markets checked: the United States, the European Union, Germany, the United Kingdom, Canada, Australia and Switzerland [34], [35], [36], [37]. The maker of cagrilintide lists the combination with semaglutide as filed for obesity, naming neither authority nor date; cagrilintide alone remains in phase 3 [10]. The maker of retatrutide announced a US application for early 2027 but had not filed it [22]. A US expanded access programme for retatrutide is not an approval [38]. In sport, both are banned at all times under section S0, which covers unapproved substances [39]. Both monographs reflect the position on 6 September 2026.
Used together?
The myPeptides blend directory lists no product that combines cagrilintide and retatrutide. Each appears there with a different partner. The entry "Cagrilintide + Semaglutide", abbreviated CagriSema, pairs cagrilintide with the GLP-1 drug semaglutide. The entry "Loretta" pairs retatrutide with eloralintide, another amylin analogue; both of its components are in phase 3 and approved nowhere.
No study of cagrilintide and retatrutide given together could be found in the sources reviewed for this page. The combination that has been tested in trials is cagrilintide with semaglutide [18], [19].
Frequently asked questions
Which is better, cagrilintide or retatrutide?
The evidence does not say. In a mid-stage trial of 706 adults without diabetes, cagrilintide on its own lowered weight by up to 10.8% over 26 weeks. Retatrutide was not part of that trial; in its own mid-stage trial of 338 adults with obesity, its highest dose lowered weight by 24.2% over 48 weeks. No study comparing the two directly could be found.
Is cagrilintide or retatrutide safer?
No study comparing their safety directly could be found, and both records come only from the manufacturers' own trials. With both, stomach and bowel complaints such as nausea come first. Retatrutide's record also includes a faster pulse and odd skin sensations. For cagrilintide, open questions concern its effect on bone and whether its appetite effect partly reflects an unpleasant sensation.
What is the difference between cagrilintide and retatrutide?
Cagrilintide copies amylin and acts on the amylin receptors and the calcitonin receptor. Retatrutide acts on the receptors for three different hormones, GIP, GLP-1 and glucagon. Cagrilintide is developed mainly in a combination with semaglutide, retatrutide as a single substance. Neither is approved anywhere.
Can cagrilintide and retatrutide be taken together?
No study of the two given together could be found in the sources reviewed for this page, and the myPeptides blend directory lists no product that combines them. The directory pairs each with a different partner: cagrilintide with semaglutide as CagriSema, and retatrutide with eloralintide as Loretta. Both substances are experimental and approved nowhere.
Is cagrilintide the same as CagriSema?
No. Cagrilintide is one substance. CagriSema is a fixed combination of cagrilintide and semaglutide, a GLP-1 drug. Most widely quoted figures, such as 20.4% weight loss over 68 weeks, belong to the combination. Cagrilintide alone reached 10.8% in its largest published trial.
Are cagrilintide and retatrutide approved anywhere?
No. As checked on 6 September 2026, none of the drug registers reviewed listed an approval for either. The maker of cagrilintide describes the combination with semaglutide as filed for obesity, without naming the authority or the date. The maker of retatrutide announced a US application for early 2027 but had not filed it.
Are cagrilintide and retatrutide banned in sport?
Yes, both at all times, in and out of competition. Section S0 of the 2026 prohibited list covers every substance that no health authority has approved for human use. Neither is named on the list; both fall under the ban because of their unapproved status.
How long do cagrilintide and retatrutide stay in the body?
The body takes roughly seven to eight days to clear half a dose of cagrilintide; the measured half-life was 159 to 195 hours. For retatrutide it takes about six days. In both, a fatty acid chain makes the peptide cling to albumin, a carrier protein in the blood, which slows its removal.
Sources
Two original titles below contain dose figures. They are given without those figures and marked as such; authors, year, journal, volume, pages and identifiers are unchanged.
- Kruse T et al. (2021). Development of cagrilintide, a long-acting amylin analogue. Journal of Medicinal Chemistry. PMID 34288673. DOI 10.1021/acs.jmedchem.1c00565
- FDA Global Substance Registration System. Substance record "Cagrilintide", UUID 524748b5-2a42-4b81-822e-35062e471925, UNII AO43BIF1U8; protein subtype amylin analog. Retrieved 6 September 2026. https://gsrs.ncats.nih.gov/api/v1/substances(524748b5-2a42-4b81-822e-35062e471925)?view=full
- FDA Global Substance Registration System. Substance record "Retatrutide", UUID 52f7c547-14ed-454d-9bc2-c9137d0b5922, UNII NOP2Y096GV. Retrieved 6 September 2026. https://gsrs.ncats.nih.gov/api/v1/substances(52f7c547-14ed-454d-9bc2-c9137d0b5922)?view=full
- Coskun T et al. (2022). LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metabolism 34(9):1234-1247. PMID 35985340. DOI 10.1016/j.cmet.2022.07.013
- Gingell JJ et al. (2021). AM833 is a novel agonist of calcitonin family G protein-coupled receptors: pharmacological comparison with six selective and nonselective agonists. Journal of Pharmacology and Experimental Therapeutics. PMID 33727283. DOI 10.1124/jpet.121.000567
- Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors (2025). Nature Communications. PMID 40204768. DOI 10.1038/s41467-025-58680-y
- Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3 (2025). EBioMedicine. PMID 40609154. DOI 10.1016/j.ebiom.2025.105836
- Beyond GLP-1: amylin-based pharmacotherapy and the search for better-tolerated weight-loss drugs (2026). Pharmacological Research. PMID 42586227. DOI 10.1016/j.phrs.2026.108382
- Urva S et al. (2023). The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptying. Diabetes, Obesity and Metabolism 25(9):2784-2788. PMID 37311727. DOI 10.1111/dom.15167
- Novo Nordisk. Research and development pipeline; entries for CagriSema in obesity (filed), CagriSema in type 2 diabetes (phase 3), cagrilintide in obesity (phase 3) and subcutaneous zenagamtide. Manufacturer communication, retrieved 6 September 2026. https://www.novonordisk.com/science-and-technology/r-d-pipeline.html
- Enebo LB et al. (2021). Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide for weight management: a randomised, controlled, phase 1b trial (title given without its dose figure). The Lancet 397(10286):1736-1748. PMID 33894838. DOI 10.1016/S0140-6736(21)00845-X
- Urva S et al. (2022). LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. The Lancet 400(10366):1869-1881. PMID 36354040. DOI 10.1016/S0140-6736(22)02033-5
- ClinicalTrials.gov API v2. Study records for NCT03841630, NCT04143802, NCT04867785, NCT04881760, NCT05882045, NCT05929066, NCT05929079, NCT05931367, NCT05936151, NCT06260722, NCT06297603, NCT06354660, NCT06383390, NCT06662383, NCT06859268, NCT07035093 and NCT07165028. Retrieved 6 September 2026. https://clinicaltrials.gov/api/v2/studies/NCT05929066
- Lau DCW et al. (2021). 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 398(10317):2160-2172. PMID 34798060. DOI 10.1016/S0140-6736(21)01751-7
- Jastreboff AM et al. (2023). Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. New England Journal of Medicine 389(6):514-526. PMID 37366315. DOI 10.1056/NEJMoa2301972
- Eli Lilly and Company. Press release, 21 May 2026, TRIUMPH-1 topline results. https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html
- Cagrilintide and CagriSema for weight reduction and metabolic risk modification in overweight or obesity: a systematic review and meta-analysis (2026). Journal of Diabetes and Metabolic Disorders. PMID 42180166. DOI 10.1007/s40200-026-01942-3
- Garvey WT et al. (2025). Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). New England Journal of Medicine 393(7):635-647. PMID 40544433. DOI 10.1056/NEJMoa2502081
- Davies MJ et al. (2025). Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2). New England Journal of Medicine 393(7):648-659. PMID 40544432. DOI 10.1056/NEJMoa2502082
- Frias JP et al. (2023). Efficacy and safety of co-administered once-weekly cagrilintide with once-weekly semaglutide in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial (title given without its dose figures). The Lancet 402(10403):720-730. PMID 37364590. DOI 10.1016/S0140-6736(23)01163-7
- Rosenstock J et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. The Lancet 402(10401):529-544. PMID 37385280. DOI 10.1016/S0140-6736(23)01053-X
- Eli Lilly and Company. Press release, 23 July 2026, TRIUMPH-2 and TRIUMPH-3 topline results and announced regulatory submission. https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html
- Cagrilintide is not associated with clinically relevant QTc prolongation: a thorough QT study in healthy participants (2024). Diabetes, Obesity and Metabolism 26:5919-5926. PMID 39279639. DOI 10.1111/dom.15951
- ClinicalTrials.gov API v2. Study records retrieved for the intervention terms cagrilintide, AM833, NNC0174-0833 and CagriSema, 53 entries in total, including NCT02300844, NCT05669755 (REDEFINE 3), NCT06131437 (REDEFINE 4), NCT05996848 (REDEFINE 6), NCT06534411 (REIMAGINE 5), NCT07220642 (RENEW 1), NCT07253285 and NCT07010432. Retrieved 6 September 2026. https://clinicaltrials.gov/api/v2/studies?query.intr=cagrilintide
- ClinicalTrials.gov. NCT06383390, TRIUMPH-Outcomes; n = 10,000, primary completion February 2029. Retrieved 6 September 2026. https://clinicaltrials.gov/study/NCT06383390
- Sanyal AJ et al. (2024). Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nature Medicine 30(7):2037-2048. PMID 38858523. DOI 10.1038/s41591-024-03018-2
- CagriSema reduces blood pressure in adults with overweight or obesity: REDEFINE 1 (2026). Hypertension. PMID 41328546. DOI 10.1161/HYPERTENSIONAHA.125.26055
- Eli Lilly and Company. Press release, 11 December 2025, TRIUMPH-4 topline results. https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-weight-loss-of-up-to-an-average-of-71-2-lbs-along-with-substantial-relief-from-osteoarthritis-pain-in-first-successful-phase-3-trial-302638804.html
- Efficacy and safety of cagrilintide and cagrisema versus semaglutide as anti-obesity medications: a systematic review, meta-analysis and meta-regression (2026). Diabetes, Obesity and Metabolism. PMID 41834765. DOI 10.1111/dom.70667
- Amyloidogenicity of peptides targeting diabetes and obesity (2022). Colloids and Surfaces B: Biointerfaces. PMID 34715595
- Expert Opinion on Investigational Drugs (2023). Retatrutide showing promise in obesity (and type 2 diabetes). PMID 37947489
- Expert Opinion on Investigational Drugs (2023). Retatrutide: a triple incretin receptor agonist for obesity management. PMID 37902090
- Cureus (2026). Online-sourced retatrutide complicating impending diabetic ketoacidosis in a patient with type 1 diabetes and concurrent Shigella gastroenteritis. PMID 42669023
- openFDA. Drugs@FDA and label API queries for generic name "cagrilintide" and brand name "cagrisema"; all responses NOT_FOUND. Retrieved 6 September 2026. https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:cagrilintide
- European Medicines Agency. Medicines search, full text "cagrilintide"; no authorised medicine entry. Retrieved 6 September 2026. https://www.ema.europa.eu/en/medicines?search_api_fulltext=cagrilintide
- openFDA. Drugs@FDA API query for generic name and brand name "retatrutide"; response NOT_FOUND. Retrieved 6 September 2026. https://api.fda.gov/drug/drugsfda.json?search=openfda.generic_name:retatrutide+OR+openfda.brand_name:retatrutide
- European Medicines Agency. Medicines search, full text "retatrutide"; no authorised medicine entry. Retrieved 6 September 2026. https://www.ema.europa.eu/en/medicines?search_api_fulltext=retatrutide
- ClinicalTrials.gov. NCT07629401, Pre-approval Expanded Access of Retatrutide (LY3437943); status AVAILABLE. Retrieved 6 September 2026. https://clinicaltrials.gov/study/NCT07629401
- World Anti-Doping Agency. The 2026 Prohibited List, in force from 1 January 2026; official text as annex to BGBl. III No. 219/2025; sections S0 and S2 reviewed in full. Retrieved 6 September 2026. https://rdb.manz.at/__api/documents/ris.c.BGBl__III_Nr__219_2025/attachments/ris.c.BGBl__III_Nr__219_2025.Anlagen_0002_F0BD5BBE_465B_4C18_BFE4_16E75843E435.pdf