Amylin is a hormone the pancreatic beta cell releases alongside insulin after a meal. It slows gastric emptying, suppresses glucagon, and ends eating episodes through a route that has nothing to do with the incretin receptors described in the mechanism article. The effect on meal size is rapid and short-lasting, tracks the meal-induced rise in circulating amylin, and is mediated centrally rather than by peripheral receptors, with the area postrema in the caudal hindbrain identified as a key site.[1] That is a second satiety lever, and the entire commercial interest in this class rests on the premise that pulling it does something the first lever does not.
The receptor has been drugged before. What that attempt produced, and how far it sits from the figures now attached to the word amylin, is the most useful thing in the published record.
The approved one, and what it actually did
Pramlintide is a synthetic 37-amino-acid polypeptide that differs from human amylin by the replacement of three residues with proline, at positions 25, 28 and 29.[7] It was approved as an adjunct to insulin, not as a weight drug, and the obesity question was tested separately.
A phase 2 trial randomized 204 adults with obesity, with and without type 2 diabetes and none of them on insulin, to pramlintide at up to 240 mcg three times daily before meals or to placebo for 16 weeks, with no concomitant lifestyle intervention. Placebo-corrected weight reduction was 3.7 ± 0.5% (3.6 ± 0.6 kg; P < 0.001) and waist circumference fell 3.6 ± 1.1 cm (P < 0.01). About 31% of treated participants reached a 5% reduction against 2% on placebo, and 88% managed the escalation to the top dose.[2]
A longer trial randomized 411 adults with obesity across six pramlintide regimens or placebo alongside a structured lifestyle program for four months, with an eight-month extension. Placebo-corrected loss at month 4 was 3.1 ± 1.1% at 120 mcg three times daily and 3.1 ± 1.0% at 360 mcg twice daily; by month 12 those figures were 5.6 ± 2.1% and 6.8 ± 2.3%, with 40% and 43% of participants reaching a 10% reduction against 12% on placebo.[3]
The denominator is the part worth holding. Those 12-month figures rest on 146 evaluable participants out of 411 randomized — roughly two in three people are not in the number.[3] It is the same problem that shadows every long obesity trial, and it is why an estimand that counts only the people who stayed reads higher than one that counts everybody.
Nausea was not the mechanism, and the trial says so
The folk explanation of this entire drug class is that people eat less because they feel sick. The 16-week pramlintide trial reported the test directly: participants who did not report nausea lost 3.6 ± 0.5% of body weight and participants who did lost 3.9 ± 0.5%.[2] Those are indistinguishable. Whatever amylin agonism is doing to appetite, it is not operating through making people queasy, and the same distinction between a side effect and a mechanism is drawn in the nausea article.
What the register says about the only approval
All three pramlintide products sit under a single application, 021332, approved in March 2005 and September 2007. The Orange Book product file records every one of them with a marketing status of discontinued, and no abbreviated application for pramlintide appears anywhere in that file.[8] Drugs@FDA returns the same status.
So the position of this class, stated plainly: one molecule has ever been approved against the amylin receptor in the United States, it produced single-digit weight reduction on a three-times-daily schedule, and it is no longer marketed. Everything else discussed under the word amylin is in development. What that phrase does and does not mean is the subject of the approval-status article.
The long-acting analogs, given alone
Cagrilintide is the one with the largest monotherapy trial. A dose-finding phase 2 at 57 sites in ten countries randomized 706 adults without diabetes 6:1 to weekly cagrilintide at 0.3, 0.6, 1.2, 2.4 or 4.5 mg, to once-daily liraglutide 3.0 mg, or to placebo for 26 weeks. On the trial product estimand, weight reduction ran from 6.0% at the bottom dose to 10.8% (11.5 kg) at 4.5 mg against 3.0% (3.3 kg) on placebo.[4]
The active comparator is the number that matters. Cagrilintide 4.5 mg against liraglutide 3.0 mg was 10.8% against 9.0% — an estimated treatment difference of 1.8 percentage points, p = 0.03.[4] A new weekly molecule beat a daily one that had been on pharmacy shelves since 2014 by under two points, which is the comparison covered from the other side in the liraglutide article. Permanent discontinuation ran 10% across groups, 4% of it for adverse events.[4]
Eloralintide is a selective amylin receptor agonist and the only analog with a 48-week randomized monotherapy result in print. A phase 2 trial randomized 263 adults at 46 United States centers to placebo or to weekly eloralintide at 1, 3, 6 or 9 mg, or to escalations of 6–9 mg or 3–9 mg. Mean weight change on the efficacy estimand was −9% (95% CI, −12.6 to −6.3) at 1 mg, −12% (−14.9 to −9.8) at 3 mg, −18% (−20.7 to −14.5) at 6 mg and −20% (−22.7 to −17.5) at 9 mg, against −0.4% (−2.2 to 1.4) on placebo.[5]
Petrelintide has only phase 1 data. Two randomized, placebo-controlled trials covered single doses from 0.04 to 2.4 mg and sixteen weekly doses escalated to targets of 2.4, 4.8 and 9.0 mg. Body weight fell by up to 8.6% after 16 weeks, the half-life ran about 10 days, nausea occurred in 16.7% to 33.3% of petrelintide recipients against 16.7% on placebo in the multiple-dose part, and one participant discontinued for gastrointestinal events.[6] That is a tolerability signal from a study designed to produce one, in a sample sized for safety rather than for effect.
The tolerability claim, tested against its own numbers
This class is marketed on being easier to take than the incretins, and the mechanistic case for that is real: receptor selectivity, exposure kinetics and whether a compound also engages the calcitonin receptor may determine whether reduced eating reflects physiological satiation or aversive signaling, and those properties differ compound by compound.[9] The class-level generalization is what the data do not support.
In the eloralintide trial, nausea ran 11% at 1 mg, 13% at 3 mg, 64% at 6 mg, 33% at 9 mg, 54% on the 6–9 mg escalation and 25% on the 3–9 mg escalation, against 14% on placebo.[5] The dose with less weight loss had roughly twice the nausea of the dose with more. The 6 mg arm held 28 people, so the figure is unstable, but the shape of it is the point: nausea did not track dose, and the schedule that reached the top dose gradually reported less of it than the one that sat at 6 mg.
Fatigue moved the other way and moved steadily: 0% at 1 mg, 13% at 3 mg, 29% at 6 mg and 43% at 9 mg, against 12% on placebo.[5] Two in five people on the top dose reported it. Fatigue on these drugs is covered in the fatigue article, and a 43% rate is not a footnote to a 20% weight figure.
Where the field is, with the certainty attached
A 2026 network meta-analysis pooled six trials and 4,642 participants across 12 to 68 weeks. It ranked high-dose subcutaneous amycretin first at −23.95% against placebo, high-dose eloralintide second at −18.01% and high-dose cagrilintide-semaglutide third at −17.18%, all ahead of semaglutide 2.4 mg at −11.45% and liraglutide 3.0 mg at −6.4%. Gastrointestinal events, nausea, vomiting and constipation were all more common with the high-dose amylin-based arms, and only high-dose cagrilintide-semaglutide increased discontinuation for adverse events. The authors describe the network as sparse and low-certainty and the findings as preliminary.[10] Six trials is a hypothesis about what to test next, not a ranking to prescribe from.
Three absences define the rest. No amylin analog has published a phase 3 monotherapy result, so every figure above comes from phase 1 or phase 2. No cardiovascular outcome result exists for any of them. And no amylin analog other than pramlintide has ever held a United States approval, which means none of the newer ones has an approved dose, an approved indication or a contraindication list. The combination route — amylin plus a GLP-1 agonist, either as two molecules or as one — is where the larger figures come from, and it is covered in the CagriSema article and the amycretin article.
What a vial sold under one of these names would be
Because no long-acting amylin analog is a component of any FDA-approved drug, no pharmacy is preparing one against an approved reference. Compounded preparations in general are not FDA-approved, and the FDA does not review them for safety, efficacy or quality before they are dispensed. For a substance with no approved product anywhere in the country, there is additionally no label to check a concentration against and no reference standard to compare a sample with.
The practical consequence is that a purity claim about one of these peptides is an assertion rather than a finding. How figures on this site are established before publication is described in the methodology.