Peptides & growth hormone

CAGRILINTIDE

Updated · 23 sources · Editorial policy

Cagrilintide is an investigational, long-acting version of amylin, a hormone the pancreas releases together with insulin after meals. Novo Nordisk developed it as a once-weekly injection for weight management. In early research papers it was called AM833 (Fletcher et al., J Pharmacol Exp Ther 2021).

Cagrilintide is studied mainly as one half of CagriSema, a fixed-dose combination with semaglutide (the drug in Ozempic and Wegovy). The single most important fact: neither cagrilintide nor CagriSema is an FDA-approved drug. Novo Nordisk filed CagriSema with the FDA in December 2025, and the FDA states that cagrilintide “cannot be used in compounding under federal law.”

This page summarizes what the clinical trials and regulators report. It is for education only and is not medical advice.

Property Detail
Drug class Long-acting amylin analogue; agonist at amylin and calcitonin receptors
Developer Novo Nordisk (research code AM833)
Route Subcutaneous injection, once weekly
Doses studied 0.16–4.5 mg once weekly; 2.4 mg in phase 3 (alone and in CagriSema)
Half-life 159–195 h (≈ 7–8 days) with weekly dosing in a phase 1b trial
Key mechanism fact Activates all three amylin receptors and the calcitonin receptor (a nonselective agonist, unlike pramlintide)
US status Not FDA-approved; CagriSema NDA submitted December 2025; FDA says it cannot be compounded
WADA status Not named on the 2026 List; as an unapproved drug it falls under S0 (non-approved substances), prohibited at all times

What it is

Amylin is a 37-amino-acid peptide hormone released together with insulin from pancreatic beta cells in response to food. It acts in the brain to help regulate food intake, body weight and blood sugar (Nielsen et al., Clin Pharmacokinet 2026). Native amylin is a difficult drug candidate because it tends to clump into amyloid fibrils. An earlier amylin analogue, pramlintide, is approved for diabetes but must be injected three times a day because of its short half-life (Kruse et al., J Med Chem 2021).

Novo Nordisk built cagrilintide on the pramlintide backbone and added several changes (Kruse et al., J Med Chem 2021; Cao et al., Nat Commun 2025; Nielsen et al., 2026):

  • amino acid substitutions, including a pair (N14E and V17R) that stabilizes the peptide’s helix to counter fibril formation; overall it shares 84% of its sequence with human amylin;
  • a lipid chain at the N-terminus (a γ-glutamate linker plus a C20 fatty diacid), part of the changes made to extend its half-life;
  • the disulfide bridge between cysteines 2 and 7 and the amidated C-terminus found in amylin-based peptides.

PubChem lists its formula as C₁₉₄H₃₁₂N₅₄O₅₉S₂ with a molecular weight of about 4,409 g/mol (PubChem).

Mechanism

Amylin receptors are pairs of proteins: the calcitonin receptor combined with one of three receptor activity-modifying proteins (RAMPs), giving the AMY1, AMY2 and AMY3 receptors. Cagrilintide activates all three amylin receptors and the calcitonin receptor itself, which is why it is called a dual amylin and calcitonin receptor agonist. Cryo-electron microscopy structures of cagrilintide bound to each of these receptors were published in 2025 (Cao et al., Nat Commun 2025).

In mice lacking RAMP1 and RAMP3 (and so lacking AMY1 and AMY3 receptors), cagrilintide lost much of its weight-lowering effect. It also activated neurons in the brainstem’s dorsal vagal complex, an appetite-regulating area (Carvas et al., EBioMedicine 2025). These are animal findings.

Semaglutide works through a different receptor, the GLP-1 receptor. The rationale for CagriSema is that the two drugs may have complementary effects on appetite and blood sugar (Nielsen et al., Clin Pharmacokinet 2026).

Pharmacokinetics

Human pharmacokinetic data come from Novo Nordisk’s early-phase trials:

Study Design Half-life Time to peak
Phase 1b, with semaglutide 2.4 mg (Enebo et al., Lancet 2021) Weekly cagrilintide 0.16–4.5 mg for 20 weeks, n=95 159–195 h Median 24–72 h
Renal impairment study (Nielsen et al., 2026) Single 0.6 mg dose, n=33 186 h (normal kidney function) to 211 h (severe impairment) Median 48–72 h
Hepatic impairment study (Nielsen et al., 2026) Single 0.9 mg dose, n=32 174 h (normal liver function) to 199 h (severe impairment) Median 36–84 h

Key points from these studies:

  • Once-weekly profile. A half-life of about 7–8 days supports weekly dosing.
  • Dose-proportional exposure. In the phase 1b trial, exposure rose in proportion to the cagrilintide dose, and cagrilintide did not change semaglutide exposure or elimination.
  • Kidney and liver impairment. Total exposure did not change in a clinically relevant way with mild, moderate or severe kidney or liver impairment. The authors concluded that dose adjustment did not appear necessary, while noting the small sample sizes.

Regulatory status

  • United States. On December 18, 2025, Novo Nordisk announced that it had submitted a New Drug Application to the FDA for CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg, once weekly) for chronic weight management in adults with obesity, or overweight with at least one weight-related condition. The company stated that “CagriSema is not approved in the US or EU” (Novo Nordisk, 2025).
  • Compounding. FDA states that “retatrutide and cagrilintide cannot be used in compounding under federal law,” and that they “have not been found safe and effective for any condition” (FDA, 2026).
  • “Research use only” products. In December 2024 FDA issued warning letters to online sellers of peptides, including cagrilintide, labeled “research use only.” FDA found that the companies’ websites and social media showed the products were intended for human use, which made them unapproved new drugs (FDA warning letter, 2024).

What the research shows

Cagrilintide alone: phase 2 dose-finding trial

The first large trial of cagrilintide on its own randomized 706 adults without diabetes to one of five weekly doses, plus 99 to daily liraglutide 3.0 mg and 101 to placebo, for 26 weeks (Lau et al., Lancet 2021). Participants had a BMI of at least 30, or at least 27 with high blood pressure or abnormal blood lipids.

Arm Mean weight change at 26 weeks
Placebo −3.0% (3.3 kg)
Cagrilintide 0.3–4.5 mg (range across doses) −6.0% to −10.8% (6.4–11.5 kg)
Cagrilintide 4.5 mg −10.8% (11.5 kg)
Liraglutide 3.0 mg daily −9.0% (9.6 kg)

These figures assume participants stayed on treatment (the trial product estimand). Every cagrilintide dose beat placebo (p under 0.001), and the 4.5 mg dose beat liraglutide by 1.8 percentage points (p = 0.03). The trial was short and was not designed to test long-term weight maintenance.

Cagrilintide alone in REDEFINE 1

The phase 3 REDEFINE 1 trial included a cagrilintide 2.4 mg monotherapy arm of 302 people (see the next section). Over 68 weeks, mean weight change assuming people stayed on treatment was (Busetto et al., Diabetes Obes Metab 2026; Verma et al., Hypertension 2026):

Arm (once weekly) n Mean weight change at 68 weeks
CagriSema 2.4 mg/2.4 mg 2,108 −22.7%
Semaglutide 2.4 mg 302 −16.1%
Cagrilintide 2.4 mg 302 −11.8%
Placebo 705 −2.3%

The share of participants reaching both a BMI under 27 and a waist-to-height ratio under 0.53 at week 68 was 30.3% with CagriSema, 19.1% with semaglutide, 9.0% with cagrilintide and 3.3% with placebo (Busetto et al., 2026).

CagriSema in obesity without diabetes (REDEFINE 1)

REDEFINE 1 was a 68-week, double-blind phase 3a trial in 3,417 adults without diabetes, randomized 21:3:3:7 to CagriSema, semaglutide, cagrilintide or placebo, all with lifestyle support (Garvey et al., NEJM 2025). Analyzed regardless of whether people stopped treatment (the treatment-policy estimand):

Outcome CagriSema Placebo
Mean weight change at 68 weeks −20.4% −3.0%
Difference vs placebo −17.3 points (95% CI −18.1 to −16.6) —
Lost at least 5% of body weight 91.9% 31.5%
Gastrointestinal adverse events 79.6% 39.9%
Stopped because of adverse events 5.9% 3.5%

The 5% responder and discontinuation figures are from Novo Nordisk’s FDA filing announcement (Novo Nordisk, 2025). Systolic blood pressure fell by 10.9 mm Hg with CagriSema vs 2.8 mm Hg with placebo (Verma et al., Hypertension 2026).

CagriSema in type 2 diabetes

Trial Design Main result
Phase 2 (Frias et al., Lancet 2023) 92 adults with type 2 diabetes on metformin; CagriSema vs semaglutide vs cagrilintide, all 2.4 mg, 32 weeks HbA1c −2.2, −1.8 and −0.9 points; weight −15.6%, −5.1% and −8.1%
REDEFINE 2 (Davies et al., NEJM 2025) 1,206 adults with obesity and type 2 diabetes; CagriSema vs placebo, 68 weeks Weight −13.7% vs −3.4% (difference −10.4 points, 95% CI −11.2 to −9.5); HbA1c 6.5% or lower in 73.5% vs 15.9%
REIMAGINE 2 (Buse et al., Lancet Diabetes Endocrinol 2026) 2,713 adults with type 2 diabetes; included a cagrilintide 2.4 mg arm (n=152); 68 weeks HbA1c −1.91 points with CagriSema vs −1.75 with semaglutide 2.4 mg (difference −0.16, 95% CI −0.27 to −0.05)

In the phase 2 diabetes trial, cagrilintide alone lowered HbA1c (HbA1c is a measure of average blood sugar over about three months) much less than semaglutide but produced more weight loss than semaglutide at 32 weeks. No level 2 or 3 hypoglycemia (clinically significant or severe low blood sugar) was reported in any arm.

Head-to-head with semaglutide in east Asia (REDEFINE 5)

In 331 adults in Japan and Taiwan, CagriSema produced a mean weight change of −18.4% vs −11.9% with semaglutide 2.4 mg at 68 weeks (difference −6.5 points, 95% CI −8.4 to −4.6) (Yamauchi et al., Lancet Diabetes Endocrinol 2026).

What is still unknown

  • Cardiovascular outcomes. REDEFINE 3 has randomized 7,076 adults with established cardiovascular disease to CagriSema or placebo to test effects on heart attack, stroke and cardiovascular death. Results have not been reported (Cavender et al., Am Heart J 2026).
  • Cagrilintide alone over the long term. Monotherapy data come from one 26-week phase 2 trial and the smaller arms of REDEFINE 1, REIMAGINE 2 and the phase 2 diabetes trial.
  • Use outside trials. Published trials used cagrilintide from Novo Nordisk at 0.16–4.5 mg, alone or with semaglutide. Products sold outside trials have not been studied.

Side effects and risks

Gastrointestinal effects

Nausea, constipation, diarrhea and vomiting are the most common side effects, as with GLP-1 drugs. In the phase 2 monotherapy trial, gastrointestinal adverse events occurred in 41–63% of people on cagrilintide vs 32% on placebo, mainly nausea (20–47% vs 18%) (Lau et al., Lancet 2021). Injection-site reactions were also among the most frequent events. In the CagriSema trials, gastrointestinal events were reported by 72.5–79.6% of participants vs 34.4–39.9% with placebo, and were mostly transient and mild to moderate (Garvey et al., NEJM 2025; Davies et al., NEJM 2025).

Serious adverse events

A 2026 meta-analysis pooled three randomized trials (n=3,545) comparing cagrilintide or CagriSema with semaglutide. Weight loss with cagrilintide alone was comparable to semaglutide, but cagrilintide alone was associated with a higher risk of serious adverse events (RR 1.83, 95% CI 1.03–3.24). CagriSema had overall and serious adverse event rates comparable to semaglutide, but more nausea and injection-site reactions (Ahmed et al., Diabetes Obes Metab 2026). The number of serious events was small, so this estimate is imprecise.

Heart rhythm

In a thorough QT study, 105 healthy volunteers received cagrilintide escalated to 4.5 mg weekly or placebo. Cagrilintide did not cause clinically relevant prolongation of the QT interval, a marker of risk for dangerous heart rhythms (Gabe et al., Diabetes Obes Metab 2024).

Semaglutide’s risks apply to CagriSema

CagriSema contains a full 2.4 mg dose of semaglutide. Its labeled warnings, including the boxed warning about thyroid C-cell tumors seen in rodents, pancreatitis and gallbladder disease, are covered on the semaglutide page. The safety profile of CagriSema in the REIMAGINE trials was described as consistent with the GLP-1 receptor agonist class and with previous cagrilintide data (Buse et al., 2026).

Unregulated products

Because cagrilintide is not approved and cannot be legally compounded in the US, any product sold outside a clinical trial comes from outside the regulated drug supply. FDA has warned sellers of “research use only” cagrilintide that these are unapproved new drugs (FDA warning letter, 2024). Their identity, purity, dose and sterility are not verified by any regulator.

Cagrilintide is not named on the WADA Prohibited List. However, the S0 class bans “any pharmacological substance” not covered elsewhere on the List that has no current approval by any government health authority, explicitly including drugs “under pre-clinical or clinical development” (WADA 2026 Prohibited List). As an unapproved investigational drug, cagrilintide falls into that class and is prohibited at all times. Its status could change if a regulator approves it.

Anti-doping researchers have already mapped cagrilintide’s breakdown products and validated a laboratory method for detecting it (Alhalabi et al., J Pharm Biomed Anal 2026).

Key takeaways

  • A once-weekly amylin analogue. Cagrilintide is a lipidated version of pramlintide that activates amylin and calcitonin receptors and has a half-life of about 7–8 days.
  • Not an approved drug. Neither cagrilintide nor CagriSema is FDA-approved; the CagriSema application was filed in December 2025, and FDA says cagrilintide cannot be compounded.
  • Moderate effect on its own. Cagrilintide 2.4 mg alone produced about 11.8% weight loss at 68 weeks in REDEFINE 1, less than semaglutide 2.4 mg (16.1%).
  • Most data are for the combination. CagriSema produced about 20–23% weight loss in people without diabetes and about 14% in people with type 2 diabetes over 68 weeks.
  • Gastrointestinal side effects are common. Nausea affected up to 47% of people on cagrilintide alone in phase 2, and gastrointestinal events affected about 80% on CagriSema in REDEFINE 1.
  • Prohibited in sport. As an unapproved drug it falls under WADA’s S0 class, and detection methods already exist.

Sources

  1. Kruse T, Hansen JL, Dahl K, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem. 2021;64(15):11183–11194. PubMed.
  2. Cao J, Belousoff MJ, Johnson RM, et al. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. Nat Commun. 2025;16(1):3389. PubMed.
  3. Carvas AO, Leuthardt A, Kulka P, et al. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine. 2025;118:105836. PubMed.
  4. National Center for Biotechnology Information. PubChem Compound Summary for CID 171397054, Cagrilintide. PubChem.
  5. 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. PubMed.
  6. Nielsen MJF, Becker NP, Duus HHH, et al. Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide. Clin Pharmacokinet. 2026;65(7):1087–1099. PubMed.
  7. 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. PubMed.
  8. Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2025;393(7):635–647. PubMed.
  9. Busetto L, Contreras CO, Christensen MH, et al. Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1. Diabetes Obes Metab. 2026;28(10):9317–9325. PubMed.
  10. Verma S, Böttcher M, Brown P, et al. CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1. Hypertension. 2026;83(2):e26055. PubMed.
  11. 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. PubMed.
  12. Davies MJ, Bajaj HS, Broholm C, et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med. 2025;393(7):648–659. PubMed.
  13. Buse JB, Bajaj HS, Dalskov SM, et al. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study. Lancet Diabetes Endocrinol. 2026;14(8):662–677. PubMed.
  14. Yamauchi T, Becker NP, Hagemann CA, et al. Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2026;14(6):450–462. PubMed.
  15. Cavender MA, Jastreboff AM, Cheng AYY, et al. Design and baseline characteristics of the CagriSema cardiovascular outcomes trial (REDEFINE 3). Am Heart J. 2026:107626. PubMed.
  16. Ahmed M, Hassan M, Tahir M, et al. Efficacy and Safety of Cagrilintide and Cagrisema Versus Semaglutide as Anti-Obesity Medications: A Systematic Review, Meta-Analysis and Meta-Regression. Diabetes Obes Metab. 2026;28(6):4828–4836. PubMed.
  17. Gabe MBN, Fuhr R, Sinn A, et al. Cagrilintide is not associated with clinically relevant QTc prolongation: A thorough QT study in healthy participants. Diabetes Obes Metab. 2024;26(12):5805–5811. PubMed.
  18. 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. PubMed.
  19. Novo Nordisk. Novo Nordisk files for FDA approval of CagriSema, the first once-weekly combination of GLP-1 and amylin analogues for weight management. Press release, December 18, 2025. Novo Nordisk.
  20. Food and Drug Administration. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. Content current as of October 1, 2026. FDA.
  21. Food and Drug Administration. Warning letter to Summit Research Peptides (MARCS-CMS 695607). December 10, 2024. FDA.
  22. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. WADA 2026 Prohibited List.
  23. Alhalabi H, Borschel L, Le Foll C, et al. In vitro metabolic profiling of weight-loss-inducing amylin receptor agonists in the context of preventive doping research. J Pharm Biomed Anal. 2026;273:117418. PubMed.