--- title: "CagriSema: Research & Evidence | BodyHackGuide" url: https://www.bodyhackguide.co/compound/cagrisema description: "CagriSema: mechanism, clinical studies & side effects." lang: en --- Skip to content Compare notes on r/BodyHackGuide (https://reddit.com/r/bodyhackguide) Compare notes with other researchers. Join r/BodyHackGuide (https://reddit.com/r/bodyhackguide) # CagriSema Metabolic & Weight Loss (https://www.bodyhackguide.co/wiki#cat-metabolic-&-weight-loss)Phase 3 Also known as: Cagrilintide-semaglutide, Cagrilintide plus semaglutide, CagriSema 2.4 mg/2.4 mg CagriSema is Novo Nordisk's once-weekly subcutaneous combination of cagrilintide, a long-acting amylin and calcitonin receptor agonist, and semaglutide, a GLP-1 receptor agonist, developed for weight management and for type 2 diabetes. The pair was first given to people in a phase 1b trial that ran from 2018 to 2019 and was published in 2021, and has since been tested in the phase 3 REDEFINE program in obesity and the phase 3 REIMAGINE program in type 2 diabetes (PMID: 33894838, PMID: 40544433, PMID: 42251859). Price check No vendor listings yet We do not track a vendor for CagriSema yet. Compare other compounds: https://www.bodyhackguide.co/compare Half-life: In the phase 1b trial published in 2021, cagrilintide at 0.16… Route: Subcutaneous Last reviewed: Oct 21, 2026 ## Overview ### At A Glance Mechanism Two hormone systems in one weekly injection… Half-Life In the phase 1b trial published in 2021, cagrilintide at 0.16 to 4.5 mg had a half-life of 159 to 195 hours and semaglutide 2.4 mg a half-life of 145 to 165 hours, both given weekly by subcutaneous injection (PMID: 33894838) Routes Subcutaneous Potential Benefits Body weight change of 20.4% against 3.0% on placebo at 68 weeks in REDEFINE 1 Body weight change of 13.7% against 3.4% on placebo at 68 weeks in adults with type 2 diabetes in REDEFINE 2 Body weight change of 18.4% against 11.9% on semaglutide 2.4 mg at 68 weeks in REDEFINE 5 73.5% reached an HbA1c of 6.5% or less, against 15.9% on placebo, in REDEFINE 2 HbA1c fall of 1.91 percentage points against 1.75 on semaglutide 2.4 mg at 68 weeks in REIMAGINE 2 Systolic blood pressure fall of 10.9 mmHg against 2.8 mmHg on placebo at 68 weeks in REDEFINE 1 Waist circumference reduction of 4.07 cm beyond semaglutide 2.4 mg in a 2026 five-trial meta-analysis Safety Notes Common Gastrointestinal events in 72.5% to 79.6% of CagriSema groups in phase 3 (PMID: 40544433, PMID: 40544432) Nausea in 55.0% of the CagriSema arm of REDEFINE 1 against 12.6% on placebo (PMID: 42808923) Constipation in 30.7% against 11.6% on placebo in REDEFINE 1 (PMID: 42808923) Injection-site reactions, about three times as frequent as with semaglutide 2.4 mg (PMID: 42890523) Discontinuation for adverse events in 6.0% in REDEFINE 1 (PMID: 42808923) Serious No severe hypoglycaemia reported when added to basal insulin over 40 weeks in REIMAGINE 3 (PMID: 42251856) One death in REIMAGINE 3, attributed to malignancy and judged unrelated to treatment (PMID: 42251856) Whether serious adverse events or neoplasms differ from semaglutide is unresolved in pooled analysis (PMID: 42890523) No clinically relevant QTcF prolongation with cagrilintide at 4.5 mg weekly in a thorough QT study (PMID: 39279639) Cardiovascular outcomes untested in print: REDEFINE 3 has published only its design (PMID: 42838477) ### Mechanism of Action ### Two hormone systems in one weekly injection CagriSema pairs two acylated peptides that act on different receptors. Cagrilintide is a long-acting analogue of amylin, a neuroendocrine hormone co-secreted with insulin whose documented actions include suppressing glucagon secretion, delaying gastric emptying, raising energy expenditure and promoting satiety (PMID: 40332747), and cagrilintide activates amylin receptors as well as the calcitonin receptor itself. Semaglutide is an analogue of glucagon-like peptide-1 (GLP-1) and acts at the GLP-1 receptor. A 2026 review of amylin pharmacology describes cagrilintide as a dual amylin receptor and calcitonin receptor agonist co-formulated with semaglutide for once-weekly subcutaneous injection, and reports that the combination produced larger effects in trials than either component alone (PMID: 41747885). ### How cagrilintide was built to last a week Native amylin aggregates into amyloid fibrils, which blocked earlier attempts to make a long-acting version. The Novo Nordisk medicinal chemistry group reported the design of cagrilintide as a stable, lipidated amylin analogue selected for clinical development in obesity, and noted that it caused weight loss alone and in combination with semaglutide (PMID: 34288673). The same group describes pramlintide, the earlier amylin analogue, as needing three injections a day because of its short half-life; the lipidation in cagrilintide is what makes weekly dosing possible, and its measured half-life in human pharmacokinetic work was 159 to 195 hours (PMID: 34288673, PMID: 33894838). ### Where the two signals meet (animal data) Two 2026 animal studies addressed where the combination acts in the brain, and neither was done in humans. A cross-species single-cell atlas of the caudal brainstem, built from more than 530,000 cells in rat, mouse and macaque, found that cagrilintide acts on two conserved populations of calcitonin-receptor (Calcr) neurons in the dorsal vagal complex; long-term cagrilintide treatment in rats raised prolactin-releasing hormone (Prlh) expression in nucleus of the solitary tract Calcr/Prlh cells, and knocking down Prlh in that region removed the effect of cagrilintide but not the effect of semaglutide (PMID: 42260119). A separate rat study found that GLP-1 receptor-expressing and calcitonin receptor-expressing neurons in the laterodorsal tegmental nucleus are largely separate populations, and that injecting both agonists into that nucleus suppressed food intake and body weight more than either alone (PMID: 42603595). The straightforward reading of both papers is that the two drugs recruit different cells, which is the mechanistic argument for combining them. ### Energy intake and energy expenditure (rat data) A 2025 rat study measured where the weight loss comes from. CagriSema produced 12% weight loss with a 39% reduction in food intake, while pair-feeding produced less weight loss and matching the weight loss by diet alone required a 51% cut in food intake. The authors concluded that about one third of the effect in rats came from blunting the drop in energy expenditure that normally accompanies weight loss (PMID: 40629149). This has not been shown for CagriSema in humans. ### Pharmacokinetics in humans In the phase 1b trial published in 2021, cagrilintide at 0.16 to 4.5 mg had a half-life of 159 to 195 hours with a median time to peak concentration of 24 to 72 hours, and semaglutide 2.4 mg had a half-life of 145 to 165 hours. Cagrilintide exposure rose in proportion to dose and did not change semaglutide exposure or elimination, which is the pharmacokinetic basis for giving the two together once a week (PMID: 33894838). Two phase 1 studies in adults with mild, moderate or severe renal or hepatic impairment found cagrilintide exposure similar to participants with normal organ function (PMID: 42228334). ### Chemistry of a two-peptide product CagriSema has no single molecular weight, formula or CAS number because it is two separate acylated peptides given together. PubChem carries no record for the combination: a name lookup for CagriSema returns nothing, while cagrilintide resolves to CID 171397054 at 4409 g/mol with the formula C194H312N54O59S2, and semaglutide resolves to CID 56843331 at 4114 g/mol with the formula C187H291N45O59 (PubChem, queried 20 October 2026). The CAS-format synonyms on those two records are 1415456-99-3 for cagrilintide and 910463-68-2 for semaglutide. ### What the combination does not appear to add A 2026 meta-analysis of five randomised trials found no incremental glycaemic benefit for CagriSema over semaglutide 2.4 mg, with the point estimate for glycated haemoglobin at 0.07 percentage points in favour of CagriSema and its confidence interval running from a 0.14 percentage point advantage for CagriSema to a 0.01 percentage point advantage for semaglutide, an interval the authors describe as falling inside the prespecified minimal important difference (PMID: 42890523). In the 92-person phase 2 trial in type 2 diabetes, the HbA1c reduction with CagriSema was larger than with cagrilintide alone but not statistically larger than with semaglutide alone (PMID: 37364590). The extra effect of adding cagrilintide shows up mainly in body weight, not in glucose. ### Cardiac electrophysiology A thorough QT study in 105 healthy participants, with moxifloxacin as a positive control, reported no clinically relevant QTcF prolongation after cagrilintide escalated to 4.5 mg weekly (PMID: 39279639). ### Overview CagriSema is Novo Nordisk's once-weekly subcutaneous combination of cagrilintide, a long-acting amylin and calcitonin receptor agonist, and semaglutide, a GLP-1 receptor agonist, developed for weight management and for type 2 diabetes. The pair was first given to people in a phase 1b trial that ran from 2018 to 2019 and was published in 2021, and has since been tested in the phase 3 REDEFINE program in obesity and the phase 3 REIMAGINE program in type 2 diabetes (PMID: 33894838, PMID: 40544433, PMID: 42251859). In REDEFINE 1, which randomised 3,417 adults with overweight or obesity and no diabetes, the estimated mean body weight change at 68 weeks was 20.4% with CagriSema against 3.0% with placebo (PMID: 40544433). CagriSema is not an approved medicine: a search of the FDA Drugs@FDA database (openFDA, data last updated 20 October 2026) returns no cagrilintide or CagriSema record while returning six semaglutide applications, and no published report of a regulatory submission could be retrieved through PubMed. ### Potential Research Fields Obesity Type 2 diabetes Amylin pharmacology Incretin pharmacology Appetite regulation Cardiometabolic risk ## Chemical Information IUPAC Name Not yet available CAS Number Not yet available Molecular Formula Not yet available Molecular Mass Not yet available Chemical data is being compiled for this compound. ## Dosing & Protocols ### Unlock the Dosing tab Enter your email to keep reading. It is free, and it opens these tabs on every compound page in this browser. - Route You also get the free peptide cheat sheet by email. Unsubscribe anytime. Have an account? Sign in (https://www.bodyhackguide.co/auth) ## Research ### Unlock the research summary - A summary of the key research - Safety and side effects - A link to the PubMed results ## Interactions ### Interaction Matrix ### Contraindications These are cautions described in the published trials and registry records, not advice. **Pregnancy and breastfeeding.** The CagriSema trials excluded women who were pregnant, breastfeeding, intending to become pregnant, or of childbearing potential and not using a highly effective contraceptive method (ClinicalTrials.gov NCT06221969). **Severe renal impairment in the efficacy trials.** The phase 3 trial against tirzepatide in type 2 diabetes excluded an estimated glomerular filtration rate below 30 mL/min/1.73 m2 (ClinicalTrials.gov NCT06221969). Pharmacokinetics are a separate question: two dedicated phase 1 studies found cagrilintide exposure similar across normal, mild, moderate and severe renal or hepatic impairment, and the investigators concluded that dose adjustment is not warranted on pharmacokinetic grounds in those groups (PMID: 42228334). **Unstable diabetic retinopathy.** The same phase 3 trial excluded uncontrolled and potentially unstable diabetic retinopathy or maculopathy, verified by eye examination (ClinicalTrials.gov NCT06221969). **Overlapping drugs.** Both components have their own mechanism, so adding another GLP-1 receptor agonist duplicates semaglutide and adding another amylin analogue duplicates cagrilintide. In the trials, participants were not allowed other diabetes or obesity medication beyond the specified background therapy (ClinicalTrials.gov NCT06221969). **Insulin and background glucose-lowering therapy.** REIMAGINE 3 studied CagriSema added to once-daily basal insulin under trial supervision and reported no severe hypoglycaemia (PMID: 42251856). Outside that setting the interaction has not been characterised. **Children and adolescents.** No paediatric results have been published. Two phase 3 paediatric trials are recruiting, in weight management and in type 2 diabetes (ClinicalTrials.gov NCT07253285 and NCT07282613). **Sport.** A 2026 anti-doping study notes that semaglutide has been in the World Anti-Doping Agency monitoring program since 2024, and reports the first systematic metabolic characterisation of cagrilintide along with a detection method intended for sports drug testing (PMID: 41702251). Athletes under anti-doping rules should treat the status of both components as a question for their governing body. Research Disclaimer This interaction data is compiled from published research and community reports. It may not be exhaustive. Always consult a healthcare professional before combining compounds. No listings found for CagriSema. ### Sign in to leave a review Reviews on BodyHackGuide are tied to verified user accounts and moderated before publishing. Sign in (free, no spam) to share your experience with CagriSema. ### Related Compounds View All (https://www.bodyhackguide.co/wiki) ### AOD-9604 Metabolic & Weight Loss Phase 3 AOD-9604 (Anti-Obesity Drug 9604) is a synthetic 16-amino-acid peptide fragment of human growth hormone (hGH) corresponding to residues 177-191 of the hGH molecule plus a tyrosine addition at the N-terminus (sequence: Tyr-Leu-Arg-Ile-Val-Gln-Cys-Arg-Ser-Val-Glu-Gly-Ser-Cys-Gly-Phe). t½ ~30–60 minutes 250–600 mcg per injection 1 PubMed View Profile https://www.bodyhackguide.co/compound/aod-9604 ### ATX-304 Metabolic & Weight Loss Phase IIa Clinical Trials ATX-304 (also known as O-304) is an orally bioavailable, first-in-class pan-AMPK activator with a mild mitochondrial-uncoupling effect. Preclinical View Profile https://www.bodyhackguide.co/compound/atx-304 ### Cagrilintide Metabolic & Weight Loss Phase 3 Cagrilintide (also known as AM833, development code NN9838) is a long-acting amylin analog developed by Novo Nordisk as a next-generation weight-management therapy, designed to be co-administered with the GLP-1 receptor agonist semaglutide in a fixed-ratio combination known as CagriSema. t½ ~159 hours (approximately 7 days) 46 PubMed View Profile https://www.bodyhackguide.co/compound/cagrilintide ### HGH Fragment 176-191 Metabolic & Weight Loss Phase 2 HGH Fragment 176-191 (also written HGH Frag 176-191, hGH Fragment 176-191, and frequently appearing in clinical literature as AOD-9604 — "Anti-Obesity Drug 9604") is a synthetic peptide corresponding to the C-terminal 15-amino-acid region of the 191-amino-acid human growth hormone (hGH) molecule, with an additional N-terminal tyrosine residue added for stability and biological activity. t½ ~30 minutes (short plasma half-life) 250-500 mcg 2 PubMed View Profile https://www.bodyhackguide.co/compound/hgh-frag-176-191 ### Retatrutide Metabolic & Weight Loss Phase 3 Retatrutide (also coded LY3437943) is an investigational once-weekly triple-agonist at the GLP-1, GIP, and glucagon receptors. t½ ~6 days (plasma, albumin-bound) 1,000–12,000 mcg (1–12 mg) per week 135 PubMed View Profile https://www.bodyhackguide.co/compound/retatrutide ### Semaglutide Metabolic & Weight Loss FDA Approved Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a molecular weight of 4113.58 Da and CAS number 910463-68-2. t½ ~7 days (168 hours), enabled by C18 fatty diacid albumin-binding modification Diabetes (Ozempic): 250-1000 mcg weekly; Weight management (Wegovy): 2400 mcg weekly (after 16-week titration); Oral (Rybelsus): 3-14 mg daily 3,273 PubMed View Profile https://www.bodyhackguide.co/compound/semaglutide View Full Dosage Guide → Protocols, calculator & safety for CagriSema https://www.bodyhackguide.co/guides/dosage/cagrisema ### Price check No vendor listings yet See the vendor scorecard (https://www.bodyhackguide.co/vendors/scorecard) ### Research Score 30 0 PubMed results ### Quality Indicators Data Completeness 50% Description Mechanism of Action Chemical Data Dosing Protocols Safety Profile PubMed Results Interactions Vendor Listings ### Quick Facts Half-Life Administration Subcutaneous Trial Phase Phase 3 ### Safety Profile Moderate Risk Common Side Effects - • Gastrointestinal events in 72.5% to 79.6% of CagriSema groups in phase 3 (PMID: 40544433, PMID: 40544432) - • Nausea in 55.0% of the CagriSema arm of REDEFINE 1 against 12.6% on placebo (PMID: 42808923) - • Constipation in 30.7% against 11.6% on placebo in REDEFINE 1 (PMID: 42808923) - • Injection-site reactions, about three times as frequent as with semaglutide 2.4 mg (PMID: 42890523) - • Discontinuation for adverse events in 6.0% in REDEFINE 1 (PMID: 42808923) Stop Use If - Not an approved medicine: no FDA record on 20 October 2026 and no confirmed filing - Pregnancy, breastfeeding or planned pregnancy were trial exclusions (ClinicalTrials.gov NCT06221969) - No published results in children or adolescents; paediatric phase 3 trials are recruiting - No published data beyond 68 weeks of treatment Research Disclaimer This information is for educational and research purposes only. Not intended as medical advice. Consult a healthcare professional before use. ## Frequently Asked Questions What is CagriSema? CagriSema is a once-weekly subcutaneous combination of two Novo Nordisk peptides: cagrilintide, a long-acting amylin and calcitonin receptor agonist, and semaglutide, a GLP-1 receptor agonist. CagriSema is given as a fixed-dose pair, and the dose studied in most phase 3 trials is 2.4 mg of each component (PMID: 40544433). CagriSema was first tested in people in a phase 1b trial that ran from 2018 to 2019 and was published in 2021, in which everyone received semaglutide 2.4 mg and cagrilintide or placebo was added on top (PMID: 33894838). The two halves of CagriSema act on different receptors, which is the stated reason for combining them (PMID: 41747885). What did the REDEFINE 1 trial of CagriSema measure? REDEFINE 1 randomised 3,417 adults without diabetes to CagriSema, semaglutide alone, cagrilintide alone or placebo for 68 weeks, with lifestyle intervention in every group. The co-primary endpoints of REDEFINE 1 were the relative change in body weight and the proportion losing at least 5% of body weight, both against placebo. Mean body weight change in the CagriSema group was 20.4% against 3.0% on placebo on the treatment-policy estimand, and both co-primary endpoints were met. Gastrointestinal adverse events in REDEFINE 1 affected 79.6% of the CagriSema group and 39.9% of the placebo group (PMID: 40544433). Is CagriSema approved? CagriSema is not approved by the FDA. A query of the FDA Drugs@FDA database through the openFDA API on 20 October 2026, with the dataset listed as last updated that day, returned no application or active ingredient record for cagrilintide or CagriSema, while the same query form returned six semaglutide applications. Published literature agrees that CagriSema is investigational: a December 2025 review protocol states plainly that CagriSema is not approved and that several phase 3 trials are ongoing (PMID: 41371743), and an October 2026 narrative review groups CagriSema with retatrutide and survodutide as late-stage investigational agents approaching regulatory review (PMID: 42808923). No regulatory submission for CagriSema could be confirmed from the sources searched here, which were the PubMed tools and the FDA database named above. Does CagriSema work better than semaglutide alone? On body weight, the published trials favour CagriSema over semaglutide 2.4 mg. REDEFINE 5, designed as a head-to-head comparison in 331 adults in Japan and Taiwan, reported a body weight change of 18.4% with CagriSema against 11.9% with semaglutide 2.4 mg at 68 weeks (PMID: 42009015). A 2026 meta-analysis of five randomised trials in 4,746 participants found CagriSema produced 6.89 percentage points more weight loss and 7.16 kg more absolute weight loss than semaglutide 2.4 mg, with about double the chance of reaching a 20% loss (PMID: 42890523). On glucose the picture differs: the same meta-analysis found no incremental benefit for CagriSema on glycated haemoglobin, and in the 2023 phase 2 trial the HbA1c difference between CagriSema and semaglutide alone was not statistically significant (PMID: 42890523, PMID: 37364590). What are the most common adverse events reported with CagriSema? Gastrointestinal events were the most common adverse events in every published CagriSema trial. In REDEFINE 1, gastrointestinal adverse events affected 79.6% of the CagriSema group against 39.9% on placebo and were reported as mainly transient and mild to moderate (PMID: 40544433); in REDEFINE 2, in adults with type 2 diabetes, the figures were 72.5% and 34.4% (PMID: 40544432). A 2026 review of gastrointestinal effects in this drug class tabulates nausea in 55.0% and constipation in 30.7% of the CagriSema arm of REDEFINE 1, with 6.0% discontinuing for adverse events (PMID: 42808923). Compared with semaglutide 2.4 mg rather than placebo, CagriSema showed roughly three times as many injection-site reactions, while gastrointestinal events were not significantly increased in one 2026 meta-analysis and nausea was modestly increased in another (PMID: 42890523, PMID: 41834765). How does CagriSema compare with tirzepatide? No published trial answers this for CagriSema. Two phase 3 trials that randomise people to CagriSema or tirzepatide are listed as completed on ClinicalTrials.gov with no results posted: NCT06131437 in 809 adults with obesity and NCT06221969 in 1,024 adults with type 2 diabetes. Until those reports appear, any ranking of CagriSema against tirzepatide comes from indirect comparisons across separate trials, which differ in population, duration and estimand. A 2026 network meta-analysis that included CagriSema among amylin-based therapies ranked high-dose injectable amycretin first, high-dose eloralintide second and high-dose CagriSema third for percentage weight loss, and described its own evidence as sparse and of low certainty (PMID: 42175595). What is still unknown about CagriSema? No published CagriSema trial has run longer than 68 weeks, so durability and what happens after stopping are untested in print. Cardiovascular outcomes with CagriSema are being tested in REDEFINE 3, which randomised 7,076 adults with established cardiovascular disease and has published only its design and baseline characteristics, with primary completion planned for September 2027 (PMID: 42838477). Whether serious adverse events or new cancers differ between CagriSema and semaglutide was described as unresolved by the 2026 five-trial meta-analysis, which also listed body composition as undetermined (PMID: 42890523). ## Research Tools ### Peptide Calculator Reconstitution & syringe units https://www.bodyhackguide.co/tools/reconstitution ### Reconstitution Guide How to mix, step by step https://www.bodyhackguide.co/guides/how-to-reconstitute-peptides ### Nasal Spray Calc mL per actuation https://www.bodyhackguide.co/tools/intranasal ### Half-Life Visualizer Decay curves https://www.bodyhackguide.co/tools/halflife ## You may also like ### Semaglutide Metabolic & Weight Loss View product (https://www.bodyhackguide.co/buy/semaglutide) ### Tirzepatide Metabolic & Weight Loss View product (https://www.bodyhackguide.co/buy/tirzepatide) ### Retatrutide Metabolic & Weight Loss View product (https://www.bodyhackguide.co/buy/retatrutide) ### Cagrilintide Metabolic & Weight Loss View product (https://www.bodyhackguide.co/buy/cagrilintide) ## Related Compounds ### AOD-9604 Metabolic & Weight Loss Phase 3 ### ATX-304 ### Cagrilintide Metabolic & Weight Loss Phase 3 t½ ~159 hours (approximately 7 days) ### HGH Fragment 176-191 Metabolic & Weight Loss Phase 2 ### Retatrutide Metabolic & Weight Loss Phase 3 ### Semaglutide Metabolic & Weight Loss FDA Approved Free 2026 Peptide Cheat Sheet (PDF) 38 compounds and blends: vial sizes, BAC water volumes, dosing ranges and bloodwork markers. 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All rights reserved. · Terms (https://www.bodyhackguide.co/terms) · Privacy (https://www.bodyhackguide.co/privacy) ## Structured data ```json [ { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://www.bodyhackguide.co/" }, { "@type": "ListItem", "position": 2, "name": "Compounds", "item": "https://www.bodyhackguide.co/compare" }, { "@type": "ListItem", "position": 3, "name": "CagriSema" } ] }, { "@context": "https://schema.org", "@type": "MedicalWebPage", "name": "CagriSema", "description": "CagriSema is Novo Nordisk's once-weekly subcutaneous combination of cagrilintide, a long-acting amylin and calcitonin receptor agonist, and semaglutide, a GLP-1 receptor agonist, developed for weight management and for type 2 diabetes. The pair was first given to people in a phase 1b trial that ran from 2018 to 2019 and was published in 2021, and has since been tested in the phase 3 REDEFINE program in obesity and the phase 3 REIMAGINE program in type 2 diabetes (PMID: 33894838, PMID: 40544433, PMID: 42251859). In REDEFINE 1, which randomised 3,417 adults with overweight or obesity and no diabetes, the estimated mean body weight change at 68 weeks was 20.4% with CagriSema against 3.0% with placebo (PMID: 40544433). CagriSema is not an approved medicine: a search of the FDA Drugs@FDA database (openFDA, data last updated 20 October 2026) returns no cagrilintide or CagriSema record while returning six semaglutide applications, and no published report of a regulatory submission could be retrieved through PubMed.", "lastReviewed": "2026-10-21T06:24:38.967Z", "url": "https://www.bodyhackguide.co/compound/cagrisema", "author": { "@type": "Person", "name": "BioChonch", "url": "https://www.bodyhackguide.co/about", "jobTitle": "Founder & Lead Researcher", "sameAs": [ "https://reddit.com/r/BodyHackGuide", "https://reddit.com/r/BrainHackGuide", "https://reddit.com/r/Biohackingher" ], "worksFor": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" } }, "reviewedBy": { "@type": "Person", "name": "BioChonch", "url": "https://www.bodyhackguide.co/about", "jobTitle": "Founder & Lead Researcher", "sameAs": [ "https://reddit.com/r/BodyHackGuide", "https://reddit.com/r/BrainHackGuide", "https://reddit.com/r/Biohackingher" ], "worksFor": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" } }, "publisher": { "@type": "Organization", "name": "BodyHackGuide", "url": "https://www.bodyhackguide.co" }, "mainContentOfPage": { "@type": "WebPageElement", "cssSelector": "main" }, "about": { "@type": "Drug", "name": "CagriSema", "alternateName": [ "Cagrilintide-semaglutide", "Cagrilintide plus semaglutide", "CagriSema 2.4 mg/2.4 mg" ], "description": "CagriSema is Novo Nordisk's once-weekly subcutaneous combination of cagrilintide, a long-acting amylin and calcitonin receptor agonist, and semaglutide, a GLP-1 receptor agonist, developed for weight management and for type 2 diabetes. The pair was first given to people in a phase 1b trial that ran from 2018 to 2019 and was published in 2021, and has since been tested in the phase 3 REDEFINE program in obesity and the phase 3 REIMAGINE program in type 2 diabetes (PMID: 33894838, PMID: 40544433, PMID: 42251859). In REDEFINE 1, which randomised 3,417 adults with overweight or obesity and no diabetes, the estimated mean body weight change at 68 weeks was 20.4% with CagriSema against 3.0% with placebo (PMID: 40544433). CagriSema is not an approved medicine: a search of the FDA Drugs@FDA database (openFDA, data last updated 20 October 2026) returns no cagrilintide or CagriSema record while returning six semaglutide applications, and no published report of a regulatory submission could be retrieved through PubMed.", "activeIngredient": "CagriSema", "administrationRoute": "Subcutaneous", "mechanismOfAction": "Two hormone systems in one weekly injection CagriSema pairs two acylated peptides that act on different receptors. Cagrilintide is a long-acting analogue of amylin, a neuroendocrine hormone co-secreted with insulin whose documented actions include suppressing glucagon secretion, delaying gastric emptying, raising energy expenditure and promoting satiety (PMID: 40332747), and cagrilintide activates amylin receptors as well as the calcitonin receptor itself. Semaglutide is an analogue of glucagon-like peptide-1 (GLP-1) and acts at the GLP-1 receptor. A 2026 review of amylin pharmacology describes cagrilintide as a dual amylin receptor and calcitonin receptor agonist co-formulated with semaglutide for once-weekly subcutaneous injection, and reports that the combination produced larger effects in trials than either component alone (PMID: 41747885). How cagrilintide was built to last a week Native amylin aggregates into amyloid fibrils, which blocked earlier attempts to make a long-acting version. The Novo Nordisk medicinal chemistry group reported the design of cagrilintide as a stable, lipidated amylin analogue selected for clinical development in obesity, and noted that it caused weight loss alone and in combination with semaglutide (PMID: 34288673). The same group describes pramlintide, the earlier amylin analogue, as needing three injections a day because of its short half-life; the lipidation in cagrilintide is what makes weekly dosing possible, and its measured half-life in human pharmacokinetic work was 159 to 195 hours (PMID: 34288673, PMID: 33894838). Where the two signals meet (animal data) Two 2026 animal studies addressed where the combination acts in the brain, and neither was done in humans. A cross-species single-cell atlas of the caudal brainstem, built from more than 530,000 cells in rat, mouse and macaque, found that cagrilintide acts on two conserved populations of calcitonin-receptor (Calcr) neurons in the dorsal vagal complex; long-term cagrilintide treatment in rats raised prolactin-releasing hormone (Prlh) expression in nucleus of the solitary tract Calcr/Prlh cells, and knocking down Prlh in that region removed the effect of cagrilintide but not the effect of semaglutide (PMID: 42260119). A separate rat study found that GLP-1 receptor-expressing and calcitonin receptor-expressing neurons in the laterodorsal tegmental nucleus are largely separate populations, and that injecting both agonists into that nucleus suppressed food intake and body weight more than either alone (PMID: 42603595). The straightforward reading of both papers is that the two drugs recruit different cells, which is the mechanistic argument for combining them. Energy intake and energy expenditure (rat data) A 2025 rat study measured where the weight loss comes from. CagriSema produced 12% weight loss with a 39% reduction in food intake, while pair-feeding produced less weight loss and matching the weight loss by diet alone required a 51% cut in food intake. The authors concluded that about one third of the effect in rats came from blunting the drop in energy expenditure that normally accompanies weight loss (PMID: 40629149). This has not been shown for CagriSema in humans. Pharmacokinetics in humans In the phase 1b trial published in 2021, cagrilintide at 0.16 to 4.5 mg had a half-life of 159 to 195 hours with a median time to peak concentration of 24 to 72 hours, and semaglutide 2.4 mg had a half-life of 145 to 165 hours. Cagrilintide exposure rose in proportion to dose and did not change semaglutide exposure or elimination, which is the pharmacokinetic basis for giving the two together once a week (PMID: 33894838). Two phase 1 studies in adults with mild, moderate or severe renal or hepatic impairment found cagrilintide exposure similar to participants with normal organ function (PMID: 42228334). Chemistry of a two-peptide product CagriSema has no single molecular weight, formula or CAS number because it is two separate acylated peptides given together. PubChem carries no record for the combination: a name lookup for CagriSema returns nothing, while cagrilintide resolves to CID 171397054 at 4409 g/mol with the formula C194H312N54O59S2, and semaglutide resolves to CID 56843331 at 4114 g/mol with the formula C187H291N45O59 (PubChem, queried 20 October 2026). The CAS-format synonyms on those two records are 1415456-99-3 for cagrilintide and 910463-68-2 for semaglutide. What the combination does not appear to add A 2026 meta-analysis of five randomised trials found no incremental glycaemic benefit for CagriSema over semaglutide 2.4 mg, with the point estimate for glycated haemoglobin at 0.07 percentage points in favour of CagriSema and its confidence interval running from a 0.14 percentage point advantage for CagriSema to a 0.01 percentage point advantage for semaglutide, an interval the authors describe as falling inside the prespecified minimal important difference (PMID: 42890523). In the 92-person phase 2 trial in type 2 diabetes, the HbA1c reduction with CagriSema was larger than with cagrilintide alone but not statistically larger than with semaglutide alone (PMID: 37364590). The extra effect of adding cagrilintide shows up mainly in body weight, not in glucose. Cardiac electrophysiology A thorough QT study in 105 healthy participants, with moxifloxacin as a positive control, reported no clinically relevant QTcF prolongation after cagrilintide escalated to 4.5 mg weekly (PMID: 39279639).", "legalStatus": "Not approved for human use (research chemical)", "warning": "For research purposes only. Not for human consumption." } }, { "@context": "https://schema.org", "@type": "FAQPage", "mainEntity": [ { "@type": "Question", "name": "What is CagriSema?", "acceptedAnswer": { "@type": "Answer", "text": "CagriSema is a once-weekly subcutaneous combination of two Novo Nordisk peptides: cagrilintide, a long-acting amylin and calcitonin receptor agonist, and semaglutide, a GLP-1 receptor agonist. CagriSema is given as a fixed-dose pair, and the dose studied in most phase 3 trials is 2.4 mg of each component (PMID: 40544433). CagriSema was first tested in people in a phase 1b trial that ran from 2018 to 2019 and was published in 2021, in which everyone received semaglutide 2.4 mg and cagrilintide or placebo was added on top (PMID: 33894838). The two halves of CagriSema act on different receptors, which is the stated reason for combining them (PMID: 41747885)." } }, { "@type": "Question", "name": "What did the REDEFINE 1 trial of CagriSema measure?", "acceptedAnswer": { "@type": "Answer", "text": "REDEFINE 1 randomised 3,417 adults without diabetes to CagriSema, semaglutide alone, cagrilintide alone or placebo for 68 weeks, with lifestyle intervention in every group. The co-primary endpoints of REDEFINE 1 were the relative change in body weight and the proportion losing at least 5% of body weight, both against placebo. Mean body weight change in the CagriSema group was 20.4% against 3.0% on placebo on the treatment-policy estimand, and both co-primary endpoints were met. Gastrointestinal adverse events in REDEFINE 1 affected 79.6% of the CagriSema group and 39.9% of the placebo group (PMID: 40544433)." } }, { "@type": "Question", "name": "Is CagriSema approved?", "acceptedAnswer": { "@type": "Answer", "text": "CagriSema is not approved by the FDA. A query of the FDA Drugs@FDA database through the openFDA API on 20 October 2026, with the dataset listed as last updated that day, returned no application or active ingredient record for cagrilintide or CagriSema, while the same query form returned six semaglutide applications. Published literature agrees that CagriSema is investigational: a December 2025 review protocol states plainly that CagriSema is not approved and that several phase 3 trials are ongoing (PMID: 41371743), and an October 2026 narrative review groups CagriSema with retatrutide and survodutide as late-stage investigational agents approaching regulatory review (PMID: 42808923). No regulatory submission for CagriSema could be confirmed from the sources searched here, which were the PubMed tools and the FDA database named above." } }, { "@type": "Question", "name": "Does CagriSema work better than semaglutide alone?", "acceptedAnswer": { "@type": "Answer", "text": "On body weight, the published trials favour CagriSema over semaglutide 2.4 mg. REDEFINE 5, designed as a head-to-head comparison in 331 adults in Japan and Taiwan, reported a body weight change of 18.4% with CagriSema against 11.9% with semaglutide 2.4 mg at 68 weeks (PMID: 42009015). A 2026 meta-analysis of five randomised trials in 4,746 participants found CagriSema produced 6.89 percentage points more weight loss and 7.16 kg more absolute weight loss than semaglutide 2.4 mg, with about double the chance of reaching a 20% loss (PMID: 42890523). On glucose the picture differs: the same meta-analysis found no incremental benefit for CagriSema on glycated haemoglobin, and in the 2023 phase 2 trial the HbA1c difference between CagriSema and semaglutide alone was not statistically significant (PMID: 42890523, PMID: 37364590)." } }, { "@type": "Question", "name": "What are the most common adverse events reported with CagriSema?", "acceptedAnswer": { "@type": "Answer", "text": "Gastrointestinal events were the most common adverse events in every published CagriSema trial. In REDEFINE 1, gastrointestinal adverse events affected 79.6% of the CagriSema group against 39.9% on placebo and were reported as mainly transient and mild to moderate (PMID: 40544433); in REDEFINE 2, in adults with type 2 diabetes, the figures were 72.5% and 34.4% (PMID: 40544432). A 2026 review of gastrointestinal effects in this drug class tabulates nausea in 55.0% and constipation in 30.7% of the CagriSema arm of REDEFINE 1, with 6.0% discontinuing for adverse events (PMID: 42808923). Compared with semaglutide 2.4 mg rather than placebo, CagriSema showed roughly three times as many injection-site reactions, while gastrointestinal events were not significantly increased in one 2026 meta-analysis and nausea was modestly increased in another (PMID: 42890523, PMID: 41834765)." } }, { "@type": "Question", "name": "How does CagriSema compare with tirzepatide?", "acceptedAnswer": { "@type": "Answer", "text": "No published trial answers this for CagriSema. Two phase 3 trials that randomise people to CagriSema or tirzepatide are listed as completed on ClinicalTrials.gov with no results posted: NCT06131437 in 809 adults with obesity and NCT06221969 in 1,024 adults with type 2 diabetes. Until those reports appear, any ranking of CagriSema against tirzepatide comes from indirect comparisons across separate trials, which differ in population, duration and estimand. A 2026 network meta-analysis that included CagriSema among amylin-based therapies ranked high-dose injectable amycretin first, high-dose eloralintide second and high-dose CagriSema third for percentage weight loss, and described its own evidence as sparse and of low certainty (PMID: 42175595)." } }, { "@type": "Question", "name": "What is still unknown about CagriSema?", "acceptedAnswer": { "@type": "Answer", "text": "No published CagriSema trial has run longer than 68 weeks, so durability and what happens after stopping are untested in print. Cardiovascular outcomes with CagriSema are being tested in REDEFINE 3, which randomised 7,076 adults with established cardiovascular disease and has published only its design and baseline characteristics, with primary completion planned for September 2027 (PMID: 42838477). Whether serious adverse events or new cancers differ between CagriSema and semaglutide was described as unresolved by the 2026 five-trial meta-analysis, which also listed body composition as undetermined (PMID: 42890523)." } } ] }, { "@context": "https://schema.org", "@type": "Organization", "@id": "https://www.bodyhackguide.co#organization", "name": "BodyHackGuide", "alternateName": "BHG", "url": "https://www.bodyhackguide.co", "logo": { "@type": "ImageObject", "url": "https://www.bodyhackguide.co/logo.png", "width": 512, "height": 512 }, "description": "Evidence-based research reference for peptides and nootropics. 273 compound profiles, interactive dosing calculators, vendor price comparisons, and trust-scored vendor reviews scored on a public, reproducible methodology applied to every vendor. 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