Amylin: the hormone behind the next weight-loss wave

What amylin does

Amylin is a peptide hormone that the pancreas's beta cells store and release with insulin after meals. It slows the emptying of the stomach and holds back glucagon, the hormone that raises blood sugar: in a crossover study in 14 men with type 1 diabetes, the amylin analogue pramlintide lowered mean daytime glucose from 10.2 to 8.3 mmol/L and blunted the rise of glucose and glucagon after meals, with insulin levels unchanged ¹.

Natural amylin is a poor drug. It clumps into fibrils, and pramlintide, the first workable copy, lasted only a short time in the body. The newer drugs were built to fix both: cagrilintide's design paper describes a stable, lipidated analogue made for once-weekly injection ². They also act on more than one receptor. Amylin receptors are built from the calcitonin receptor paired with partner proteins called RAMPs; in obese mice, losing RAMP1 and RAMP3 blunted cagrilintide's effect on weight ³, while eloralintide was designed to prefer the human AMY1 receptor, 12-fold over the calcitonin receptor in cell assays ⁴.

The first amylin drug: pramlintide

Pramlintide High, sold as Symlin, was approved in the US on March 16, 2005 ⁵, as a mealtime injection for people with diabetes who also used insulin. In a year-long trial in 538 insulin-treated people with type 2 diabetes, HbA1c fell by 0.9% and 1.0% at 13 weeks on the two higher doses but by 0.6% at 52 weeks on the highest, without more insulin or severe hypoglycaemia; weight fell on every dose, and nausea was the most common side effect ⁶.

It never became a weight-loss drug, and Drugs@FDA now lists every Symlin product as discontinued ⁵. What it left behind was the proof that adding amylin's signal to insulin's changes how people eat and how their blood sugar behaves after a meal.

Cagrilintide and CagriSema (Novo Nordisk)

Cagrilintide Medium is Novo Nordisk's weekly amylin analogue. In a 26-week phase 2 dose-finding trial in 706 adults, weekly doses of 0.3 to 4.5 mg reduced weight by 6.0% to 10.8% against 3.0% on placebo, and the 4.5 mg dose beat liraglutide 3.0 mg, 10.8% against 9.0%; gastrointestinal events affected 41% to 63% against 32% on placebo ⁷.

Novo's main bet is the combination with semaglutide, CagriSema. In REDEFINE 1, 3,417 adults with obesity lost 20.4% of their weight over 68 weeks against 3.0% on placebo, and gastrointestinal events affected 79.6% against 39.9%, mostly transient and mild to moderate ⁸. In REDEFINE 2, in 1,206 adults with type 2 diabetes, the loss was 13.7% against 3.4% ⁹.

Novo filed CagriSema with the FDA in December 2025, with a decision expected in late 2026 ¹⁰. In February 2026 the company reported that CagriSema had lost a head-to-head trial against Lilly's tirzepatide ¹¹. As of October 2, 2026, we found no announced FDA decision.

Petrelintide (Zealand Pharma)

Petrelintide Medium is Zealand Pharma's weekly amylin analogue. Its phase 2 trial, ZUPREME 1, randomized adults with obesity, or overweight with high blood pressure or abnormal blood lipids, to weekly petrelintide or placebo. At the primary endpoint, 28 weeks, weight fell 7.9% to 9.8% across five doses against 1.7% on placebo, and the three highest doses performed about the same; Zealand's headline figure of up to 10.7% is from week 42 ¹².

Eloralintide and EloraTZP (Eli Lilly)

Eloralintide Medium is Lilly's weekly amylin agonist. In a 12-week phase 1 trial in 100 people with obesity or overweight, started at the full dose without escalation, mean weight loss ranged from 2.6% to 11.3% across the dose groups ¹³. Its phase 2 trial enrolled 263 adults at 46 US centres with obesity or overweight and at least one weight-related condition, and no type 2 diabetes. After 48 weeks, weight fell 9%, 12%, 18% and 20% on fixed doses of 1, 3, 6 and 9 mg, 20% when escalated from 6 to 9 mg and 16% from 3 to 9 mg, against 0.4% on placebo. Nausea ranged from 11% to 64% across the groups against 14% on placebo, and fatigue reached 43% and 46% in the two 9 mg groups against 12% ¹⁴.

Lilly has moved eloralintide into five phase 3 trials, the ENLIGHTEN program; each is once weekly, double-blind and placebo-controlled, with the percentage change in body weight at week 64 as the primary endpoint ¹⁵. It is also being paired with tirzepatide as EloraTZP. Our eloralintide hub follows each trial and readout.

Amycretin (Novo Nordisk)

Amycretin Medium is different in kind: one molecule that acts on both the GLP-1 receptor and amylin receptors, tested as a weekly injection and as a daily tablet. In a phase 1b/2a trial of weekly injections in 125 adults, weight changed by -24.3% against -1.1% on placebo at the 60 mg dose and by -22.0% against +1.9% at 20 mg after 36 weeks; gastrointestinal events were the most common and mostly mild to moderate ¹⁶. In the first trial of the tablet, in 144 adults, adverse events affected 62%, all mild or moderate and more common at higher doses, and half of them were gastrointestinal ¹⁷.

Why eloralintide is already sold online

None of the four newer drugs is approved anywhere for weight loss as of October 2, 2026. Even so, products labelled eloralintide and amycretin are offered by online "research compound" sellers; a consumer health guide that covers them notes that such products are not regulated by the FDA, follow no verified manufacturing standards and carry unknown contamination and dosing risks ¹⁸. That is the same channel that sold semaglutide and tirzepatide before them, and our guide to what "research use only" means explains why the label does not make a vial safe or legal to inject.

A vial sold this way is not the drug in the trials. Nothing outside the regulated supply confirms what it contains, how much, or whether it is sterile, and the phase 2 trial reached its doses either at a fixed level or by planned escalation under medical supervision, with nausea in up to 64% of one group ¹⁴.

What to watch

Two events will set the field's direction. The first is the FDA's decision on CagriSema, which would make it the first amylin-based weight-loss drug if approved ¹⁰. The second is the eloralintide phase 3 program, whose week-64 results will show whether an amylin agonist on its own can match the GLP-1 drugs in large trials ¹⁵.

Frequently asked questions

What is amylin?

A peptide hormone that the pancreas releases with insulin after meals. It slows stomach emptying and holds back glucagon, which is why drugs that copy it can reduce appetite and blood sugar after eating.

Is any amylin drug approved for weight loss?

No, as of October 2, 2026. Pramlintide was approved for diabetes in 2005 and is now listed as discontinued. CagriSema, cagrilintide combined with semaglutide, has been under FDA review since December 2025.

How much weight do amylin drugs take off?

Alone, cagrilintide reduced weight by up to 10.8% at 26 weeks, petrelintide by 7.9% to 9.8% at 28 weeks and eloralintide by up to 20% at 48 weeks. CagriSema reached 20.4% at 68 weeks, and amycretin 24.3% at 36 weeks on its highest weekly dose.

What are the side effects of amylin drugs?

Gastrointestinal effects, mostly nausea, are the most common in every trial. In the eloralintide phase 2 trial nausea ranged from 11% to 64% across dose groups, and fatigue reached 46% in one group.

Related on Grey Peptides

• Eloralintide and EloraTZP
• CagriSema
• Pramlintide

Sources

1. Nyholm, B., et al. (1999). The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus. Metabolism, 48(7), 935-41. PMID: 10421239
2. Kruse, T., et al. (2021). Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem, 64(15), 11183-11194. PMID: 34288673
3. Carvas, A. O., et al. (2025). Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine, 118, 105836. PMID: 40609154
4. Briere, D. A., et al. (2025). Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept. Mol Metab, 102, 102271. PMID: 41109426
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6. Ratner, R. E., et al. (2002). Adjunctive therapy with the amylin analogue pramlintide leads to a combined improvement in glycemic and weight control in insulin-treated subjects with type 2 diabetes. Diabetes Technol Ther, 4(1), 51-61. PMID: 12017421
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8. Garvey, W. T., et al. (2025). Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med, 393(7), 635-647. PMID: 40544433
9. Davies, M. J., et al. (2025). Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med, 393(7), 648-659. PMID: 40544432
10. CNBC. Healthy Returns: What's next for Novo Nordisk's next-generation obesity drug CagriSema after trial miss, February 24, 2026; read October 2, 2026.
11. Clinical Trials Arena. Novo Nordisk's CagriSema bested by Lilly's Zepbound in head-to-head trial, February 23, 2026; read October 2, 2026.
12. Garvey, W. T., et al. (2026). Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol, . PMID: 42810355
13. Bhattachar, S., et al. (2026). Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: Phase 1 proof of concept. Diabetes Obes Metab, 28(4), 2651-2660. PMID: 41559929
14. Billings, L. K., et al. (2025). Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial. Lancet, 406(10520), 2631-2643. PMID: 41207310
15. ClinicalTrials.gov. Registry records for the eloralintide (LY3841136) ENLIGHTEN phase 3 program and the EloraTZP phase 2b trial NCT06603571; read October 2, 2026.
16. Dahl, K., et al. (2025). Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study. Lancet, 406(10499), 149-162. PMID: 40550231
17. Gasiorek, A., et al. (2025). Safety, tolerability, pharmacokinetics, and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist, amycretin: a first-in-human, phase 1, double-blind, randomised, placebo-controlled trial. Lancet, 406(10499), 135-148. PMID: 40550229
18. Superpower. Eloralintide and amycretin: amylin and GLP-1 receptor agonists (consumer health guide); read October 2, 2026.

Educational information, not medical advice. Each dose in this guide names its source, an approved label or a published study. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose.