Cagrilintide

Dosing from the Literature

Published for fat loss: 2.4 mg once a week, the Phase 2 and 3 dose, alone and with semaglutide. Not published: an approved dose; it isn't approved.

The doses below are the ones given in the Phase 1, 2 and 3 trials. Cagrilintide is not approved, so no labeled dose exists. This is research documentation, not medical advice.

What It Is

Cagrilintide (development code AM833, NN9838) is an investigational 37-amino-acid lipidated analog of the endogenous pancreatic hormone amylin, developed by Novo Nordisk as a once-weekly subcutaneous anti-obesity therapeutic. Native human amylin is co-secreted with insulin by pancreatic β-cells in response to meals and acts at calcitonin-receptor-based amylin receptor complexes (AMY1R, AMY2R, AMY3R) to slow gastric emptying, reduce glucagon secretion, and produce centrally-mediated satiety. Amylin's therapeutic potential has been recognized for decades — pramlintide (Symlin) is an FDA-approved short-acting amylin analog for type 1 and insulin-treated type 2 diabetes since 2005 — but pramlintide's three-times-daily dosing and fibril-formation tendency limited commercial uptake.

Cagrilintide was engineered to solve both problems simultaneously. Kruse, Hansen, Dahl and colleagues (J Med Chem 2021) described the medicinal chemistry: a stabilized amylin backbone carrying a C20 fatty diacid conjugate at a lysine position, giving reversible albumin binding; in people its half-life was 159–195 hours (Enebo et al., 2021), compatible with once-weekly dosing alongside semaglutide. The sequence also incorporates substitutions that reduce the molecule's tendency to self-associate into amyloid-like fibrils, allowing stable high-concentration SubQ formulation.

Cagrilintide’s case rests on amylin acting through receptors other than GLP-1’s, so that drugs aimed at the two may act additively (Fletcher et al., 2021). That is the rationale for CagriSema — the fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg.

The REDEFINE Phase 3 program delivered the answer in 2025. REDEFINE 1 (NCT05567796) in 3,417 adults without diabetes showed CagriSema produced 20.4% mean weight loss at 68 weeks versus 3.0% placebo. REDEFINE 2 (NCT05394519) in 1,206 adults with type 2 diabetes showed CagriSema 13.7% weight loss versus 3.4% placebo. Both trials were published simultaneously in the New England Journal of Medicine in June 2025. These results place CagriSema roughly at parity with tirzepatide (SURMOUNT-1 −20.9% at 72 weeks) in the non-diabetic obesity setting and ahead of semaglutide alone (STEP-1 −14.9% at 68 weeks). As of April 2026, CagriSema is under FDA review; cagrilintide as a solo agent is investigational.

Mechanism of Action

Cagrilintide is a stable, lipidated, long-acting analog of amylin (Kruse et al., 2021) that acts on the amylin and calcitonin receptors (Fletcher et al., 2021). With semaglutide, weight fell further than on semaglutide alone in the Phase 1b and Phase 2 trials (Enebo et al., 2021; Frias et al., 2023).

• Amylin receptor agonism (AMY1R, AMY2R, AMY3R) — The amylin receptors are the calcitonin receptor paired with one of three RAMP proteins (Hay et al., 2018); cagrilintide activates them without selectivity (Fletcher et al., 2021).
• Calcitonin receptor activity — AM833 is a novel agonist across the calcitonin family G-protein-coupled receptors, with activity at the calcitonin receptor (CTR) alongside the amylin receptors (Fletcher et al., J Pharmacol Exp Ther 2021; PMID 33727283).
• Satiety — Natural amylin is a pancreatic hormone that induces satiety (Lau et al., 2021).
• Lipidation and half-life — Cagrilintide is lipidated for a long action (Kruse et al., 2021); in people its half-life was 159–195 hours (Enebo et al., 2021), long enough for once-weekly injection.
• Separate from GLP-1 — The amylin receptors are not the GLP-1 receptor, and drugs that target them may act additively with GLP-1 drugs (Fletcher et al., 2021).
• Fibril resistance — Native amylin readily forms amyloid fibrils, which made a stable drug hard to design, and pramlintide needs three injections a day because of its short half-life; cagrilintide was developed as a stable, long-acting analog (Kruse et al., 2021).
• Glucose — In type 2 diabetes over 32 weeks, HbA1c fell 0.9 points on cagrilintide alone and 2.2 points with semaglutide, and fasting glucose fell too (Frias et al., 2023).

What the Research Shows

Cagrilintide's clinical development has been rapid and well-documented, with multiple Phase 1, 2, and 3 trials completed by 2025.

• Discovery / chemical development (Kruse J Med Chem 2021) — Published structural development of the stable, lipidated long-acting amylin analog cagrilintide.
• Receptor pharmacology (Fletcher, J Pharmacol Exp Ther 2021; PMID 33727283) — Characterized AM833 as a novel agonist across the calcitonin family GPCRs, with receptor pharmacology distinct from six comparator selective and non-selective amylin receptor agonists.
• Phase 2 dose-finding (Lau Lancet 2021) — Once-weekly cagrilintide 0.3–4.5 mg for weight management in overweight/obese adults without diabetes over 26 weeks. 706 adults; weight fell 6.0–10.8% across doses (10.8% on 4.5 mg) against 3.0% on placebo, and 9.0% on liraglutide 3.0 mg (Lau et al., 2021).
• Phase 1b combination with semaglutide (Enebo Lancet 2021; PMID 33894838) — Concomitant cagrilintide (0.16–4.5 mg) + semaglutide 2.4 mg for 20 weeks in 285 screened / 96 randomized adults. Weight loss: cagrilintide 1.2 mg + semaglutide −15.7%; cagrilintide 2.4 mg + semaglutide −17.1%; placebo + semaglutide −9.8%. Established the clinical additivity of the combination.
• Phase 2 CagriSema in T2D (Frias Lancet 2023) — Co-administered weekly cagrilintide 2.4 mg + semaglutide 2.4 mg in 92 adults with T2D, 32 weeks: weight fell 15.6%, against 5.1% on semaglutide alone and 8.1% on cagrilintide alone; HbA1c fell 2.2 points, not significantly more than on semaglutide (1.8; p=0.075) (Frias et al., 2023).
• REDEFINE 1 Phase 3 (Garvey et al., NEJM 2025) — 3,417 adults without diabetes, BMI ≥30 or ≥27 with comorbidity. 68 weeks. CagriSema (cagrilintide 2.4 mg + semaglutide 2.4 mg): −20.4% weight loss vs −3.0% placebo. ~60% achieved ≥20% weight loss; ~23% achieved ≥30% weight loss. GI adverse events common (~80% vs ~40% placebo), mostly mild-moderate and concentrated in titration.
• REDEFINE 2 Phase 3 (Davies et al., NEJM 2025; PMID 40544432) — 1,206 adults with type 2 diabetes + BMI ≥27 + HbA1c 7–10%. 68 weeks. CagriSema: −13.7% weight loss vs −3.4% placebo. HbA1c reduction confirmed.
• Long-term cardiovascular outcomes (REDEFINE-CVOT) — Cardiovascular outcomes trial ongoing for longer-term safety and MACE endpoints.
• Amycretin (unimolecular GLP-1 / amylin) — Novo Nordisk's next-generation single-molecule combining GLP-1R and amylin receptor agonism in one peptide, Phase 1b/2a data (Lancet 2025). Represents the strategic successor to CagriSema.

Human Data

Cagrilintide has accumulated one of the largest Phase 3 datasets of any investigational obesity drug:

• Phase 1 (multiple) — Pharmacokinetics, safety, dose tolerability. Half-life 159–195 hours, supporting once-weekly dosing (Enebo et al., 2021).
• Phase 1b combination (Enebo 2021, PMID 33894838) — 96 participants; CagriSema proof-of-concept.
• Phase 2 dose-finding (Lau 2021) — 706 participants; weight fell by up to 10.8% in 26 weeks (Lau et al., 2021).
• Phase 2 CagriSema in T2D (Frias 2023) — 92 adults with type 2 diabetes, 32 weeks, against semaglutide and cagrilintide alone (Frias et al., 2023).
• REDEFINE 1 Phase 3 — 3,417 adults without diabetes; pivotal non-diabetic obesity trial (NCT05567796).
• REDEFINE 2 Phase 3 — 1,206 adults with T2D; pivotal T2D trial (NCT05394519; PMID 40544432).
• REDEFINE-CVOT — Ongoing cardiovascular outcomes trial.

Reconstitution & Storage

Cagrilintide has no approved label, so no official storage or handling instructions exist. Research-chemical sellers list it as freeze-dried powder in vials; in the Phase 3 trials it is given by pen (ClinicalTrials.gov NCT05567796 lists it as a subcutaneous injection). For a mixed vial, the arithmetic depends on the vial mass, the water volume and the dose; 2.4 mg is the trial dose (see Dosing).

→ Calculator — vial-to-syringe math

Side Effects & Risks

In REDEFINE 1, gastrointestinal adverse events affected 79.6% on cagrilintide with semaglutide against 39.9% on placebo, mainly transient and mild to moderate (Garvey et al., 2025); in REDEFINE 2, 72.5% against 34.4% (Davies et al., 2025). On cagrilintide alone in Phase 2, they affected 41–63% across doses against 32% on placebo (Lau et al., 2021).

• Nausea — The most frequent: on cagrilintide alone in Phase 2, 20–47% across doses against 18% on placebo (Lau et al., 2021).
• Vomiting, diarrhea, constipation, abdominal pain — The other gastrointestinal events counted in REDEFINE 1’s 79.6% (Garvey et al., 2025); constipation and diarrhoea were among the most frequent events on cagrilintide alone (Lau et al., 2021).
• Injection site reactions — Administration-site reactions were among the most frequent adverse events on cagrilintide alone in Phase 2 (Lau et al., 2021).
• Gallbladder disease — Acute gallbladder disease is a listed warning on the label of semaglutide (Wegovy), CagriSema’s other half (Wegovy label).
• Pancreatitis — Acute pancreatitis is a listed warning on the Wegovy label (Wegovy label).
• Hypoglycemia risk — No level 2 or 3 hypoglycemia occurred in the 32-week Phase 2 trial in type 2 diabetes (Frias et al., 2023). The Wegovy label lists a higher risk of hypoglycemia when semaglutide is used with insulin or an insulin secretagogue (Wegovy label).
• Heart rate increase — A listed warning on the Wegovy label (Wegovy label).
• Thyroid C-cell / medullary thyroid concerns — Semaglutide carries a boxed warning: it caused thyroid C-cell tumors in rodents, whether it does in people is unknown, and a personal or family history of medullary thyroid carcinoma or MEN 2 is a contraindication (Wegovy label).
• Pregnancy / lactation — No published data for cagrilintide. The Wegovy label says to stop semaglutide at least 2 months before a planned pregnancy, because of its long half-life (Wegovy label).
• Drug interactions — Semaglutide delays gastric emptying, which the Wegovy label says may affect the absorption of oral medicines; the label also lists a higher risk of hypoglycemia with insulin or insulin secretagogues (Wegovy label).
• WADA status — Not named on the Prohibited List, but prohibited at all times under S0, non-approved substances, because no government has approved it for human therapeutic use (WADA Prohibited List 2026).
• Purity (gray-market) — Outside the trials, cagrilintide is sold only as a research chemical, unregulated for quality.

Quick Compare — Cagrilintide vs Semaglutide vs Tirzepatide vs Pramlintide vs Retatrutide

Cagrilintide sits in a dense competitive field. The relevant comparators are: (a) semaglutide, its CagriSema partner; (b) tirzepatide, the dual GIP/GLP-1 benchmark; (c) pramlintide, the predecessor amylin analog; (d) retatrutide, the triple-agonist competing for "most potent" weight loss.

Practical interpretation:

• CagriSema vs tirzepatide — Comparable magnitude of weight loss (20.4% vs 20.9% in non-diabetic Phase 3). Tirzepatide is approved and established; CagriSema is anticipated approval. Different receptor mechanisms (amylin+GLP-1 vs GIP+GLP-1); neither is clearly superior in published head-to-head data.
• CagriSema vs semaglutide — Weight fell 20.4% on CagriSema in REDEFINE 1 (Garvey et al., 2025) and 14.9% on semaglutide alone in STEP-1 (Wilding et al., 2021), separate trials; in Phase 2 in type 2 diabetes, CagriSema took off 15.6% against 5.1% on semaglutide alone (Frias et al., 2023).
• Solo cagrilintide vs combination — Solo cagrilintide delivers smaller weight loss than the CagriSema combination. The commercially dominant pathway is CagriSema, not cagrilintide alone.
• Cagrilintide vs pramlintide — Pramlintide was the first-generation amylin analog; pre-meal 3×/day dosing limited adoption. Cagrilintide is the once-weekly successor that completes the amylin class's long-acting transition.

→ See Semaglutide profile  •  → See Tirzepatide profile  •  → See Retatrutide profile  •  → See Pramlintide profile

Bloodwork & Monitoring

No label or guideline sets monitoring for cagrilintide, which is investigational. Its trials measured body weight, HbA1c, fasting glucose and, in two, continuous glucose monitoring (Frias et al., 2023; Davies et al., 2025), and recorded adverse events (Garvey et al., 2025).

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References

1. Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021;397(10286):1736-1748. PMID: 33894838. DOI: 10.1016/S0140-6736(21)00845-X.
2. Lau DCW, Erichsen L, Francisco AM, et al. 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. Lancet. 2021;398(10317):2160-2172. PMID: 34798060.
3. Kruse T, Hansen JL, Dahl K, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem. 2021;64(15):11183-11194. DOI: 10.1021/acs.jmedchem.1c00565.
4. Fletcher MM, Keov P, Truong TT, et al. AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists. J Pharmacol Exp Ther. 2021;377(3):417-440. PMID: 33727283.
5. Garvey WT, Blüher M, Osorto Contreras CK, Davies MJ, Winning Lehmann E, Pietiläinen KH, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1). N Engl J Med. 2025;393(7):635-647. PMID: 40544433. DOI: 10.1056/NEJMoa2502081.
6. Davies MJ, Bajaj HS, Broholm C, Eliasen A, Garvey WT, le Roux CW, et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2). N Engl J Med. 2025;393(7):648-659. PMID: 40544432. DOI: 10.1056/NEJMoa2502082.
7. Frias JP, Deenadayalan S, Erichsen L, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial. Lancet. 2023;402(10403):720-730. PMID: 37364590.
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14. ClinicalTrials.gov. REDEFINE 1 (NCT05567796) and REDEFINE 2 (NCT05394519). Novo Nordisk CagriSema Phase 3 program.
15. Dahl K, Toubro S, Dey S, Duque do Vale R, Flint A, Gasiorek A, Heydorn A, Jastreboff AM, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study. Lancet. 2025;406(10499):149-162. PMID: 40550231. (Novo Nordisk next-generation successor to CagriSema.)
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17. World Anti-Doping Agency. Prohibited List 2026 (in effect January 1, 2026). S0, Non-approved substances. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf. Read October 3, 2026.
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19. FDA. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. Content current as of October 1, 2026. fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss. Read October 4, 2026.
20. Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1). N Engl J Med. 2026 (published online September 29, 2026). PMID: 42814954. DOI: 10.1056/NEJMoa2604169.
21. Eli Lilly and Company. Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. Press release, July 23, 2026 (PR Newswire). 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. Read October 4, 2026.
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24. 21 U.S.C. 353a, Pharmacy compounding (section 503A of the Federal Food, Drug, and Cosmetic Act), United States Code, 2024 edition. https://www.govinfo.gov/content/pkg/USCODE-2024-title21/html/USCODE-2024-title21-chap9-subchapV-partA-sec353a.htm. Read October 18, 2026.
25. FDA. Bulk Drug Substances Used in Compounding Under Section 503B of the FD&C Act (503B page). https://www.fda.gov/drugs/human-drug-compounding/bulk-drug-substances-used-compounding-under-section-503b-fdc-act. Read October 18, 2026.

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