RPB

Amylin

Islet amyloid polypeptide (IAPP), diabetes-associated peptide (DAP, historical), human amylin; related drugs: pramlintide (#65), cagrilintide (#32), petrelintide (#66), eloralintide (#67)

Metabolic & weight
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1What it is

Amylin was discovered in 1987 when two groups (Cooper in Oxford, Westermark in Sweden) worked out that the protein deposits found in the pancreatic islets of people with type 2 diabetes — known since 1901 as "islet hyalinosis" — were made of a previously unknown 37-amino-acid peptide. It turned out to be a hormone in its own right, stored in the same granules as insulin and released alongside it at a ratio of roughly 1:100. Its name reflects both facts: amyloid and insulin.

Amylin's job is to complement insulin. Insulin clears glucose from the blood; amylin slows how fast glucose arrives, by delaying stomach emptying, damping the glucagon surge that follows a meal, and telling the brain the meal is big enough. People with type 1 diabetes lose amylin along with insulin, which is part of why their post-meal glucose swings are so hard to control, and was the original rationale for pramlintide.

The native hormone has a chemical liability: human amylin aggregates readily into the same amyloid fibrils found in diabetic islets, and the aggregation process is toxic to beta cells. Rodent amylin, which differs at a few positions (notably prolines in the 25–29 region), does not aggregate. Every amylin medicine is therefore an engineered analogue — pramlintide copies the rat prolines, and the newer weekly agents add fatty-acid or protein tags. Native amylin is a laboratory and physiology-study reagent only. Community/self-directed use: essentially none documented; what circulates online under "amylin" is almost always cagrilintide or another analogue.

2How it's thought to work

Receptors. amylin has no receptor of its own. It binds the calcitonin receptor when that receptor is paired with one of three "receptor activity-modifying proteins" (RAMP1–3), producing the AMY1, AMY2 and AMY3 receptor complexes. This shared machinery is why amylin analogues also touch calcitonin and CGRP biology, and why the newer "dual amylin and calcitonin receptor " (DACRAs) exist.
Brainstem satiety. the key site is the area postrema, a region outside the blood–brain barrier that senses circulating hormones. Amylin acting there reduces meal size and, with chronic exposure, lowers body weight — in rodents it also increases sensitivity to leptin, which is the mechanistic basis for combining amylin analogues with other weight-loss hormones.
Gastric emptying. slows the delivery of food to the small intestine via vagal pathways, flattening the post-meal glucose peak.
Glucagon suppression. blunts the inappropriate glucagon rise after meals in diabetes, without affecting the protective glucagon response to hypoglycaemia.
Beta-cell toxicity (pathology). misfolded human amylin oligomers damage beta cells and may contribute to the progression of type 2 diabetes — a separate, harmful face of the same molecule.
The hormone released with insulin from the same beta cell. At the calcitonin receptor paired with a RAMP protein it slows stomach emptying, signals fullness, and holds back glucagon after a meal.Schematic — not to scale

3What the research shows

Post-meal glucose and satiety with native amylin

Infusion studies in the 1990s showed that human amylin at physiological-to-high concentrations slows gastric emptying and reduces post-meal glucose and glucagon in healthy volunteers and people with type 1 diabetes (Kolterman 1995, Diabetologia, using pramlintide as a stable surrogate; earlier native-amylin infusions reviewed in Young 2005, Adv Pharmacol). Because native amylin aggregates, almost all controlled human pharmacology was in fact done with pramlintide, and the native hormone's human evidence base is mostly observational: plasma levels, response to meals, and absence in type 1 diabetes. [3]
Graded B (observational)

Amylin deficiency and excess in disease

Amylin is absent or near-absent in type 1 diabetes and in late type 2 diabetes, and raised in obesity and insulin resistance in parallel with insulin (Ludvik 1991, Diabetes). Islet amyloid is found in the majority of people with long-standing type 2 diabetes at autopsy and correlates with beta-cell loss (Jurgens 2011, Am J Pathol). [5]

Weight loss with amylin analogues

This is where the hormone's biology has been translated. Pramlintide produced modest weight loss (~1–2 kg) alongside glucose benefits in type 1 and type 2 diabetes (Hollander 2003, Diabetes Care). The long-acting analogues do far more: cagrilintide alone gave ~10% weight loss at 26 weeks (Lau 2021, Lancet) and in combination with semaglutide (CagriSema) ~20–23% at 68 weeks in REDEFINE-1 (2024–2025 †); petrelintide in ZUPREME-1 (485 adults) produced 10.7% weight loss versus 1.7% with placebo at week 42, with nausea in 19.6% versus 6.2% and only 1.5% discontinuing for GI reasons; eloralintide's Phase 2 (reported November 2025) showed 9.5–20.1% weight loss at 48 weeks across doses with favourable tolerability, and it has moved to Phase 3 †. Full detail is in the individual profiles. [8]
Graded C/B

Amylin and leptin synergy

Rodent work showed amylin restores leptin sensitivity in diet-induced obesity (Roth 2008, PNAS); a small human study of pramlintide plus metreleptin produced ~12% weight loss over 20 weeks before the programme was stopped (Ravussin 2009, Obesity). This result underpins the modern combination strategy. [6][7]
Graded C/D

Islet amyloid toxicity

Transgenic mice expressing human amylin develop islet amyloid and diabetes; rodent amylin does not aggregate. Cell studies show oligomer-induced membrane damage, ER stress and inflammasome activation (Westermark 2011, Physiol Rev; Masters 2010, Nat Immunol). [2][9]

4Reported side effects and interactions

Literature-reported

Literature (native amylin infusions). nausea at higher infusion rates, transient flushing; studies were short and small. Nausea is the class-defining effect of every amylin-receptor .

Literature (analogues). nausea, vomiting, reduced appetite, injection-site reactions; pramlintide carries a boxed warning for severe insulin-induced hypoglycaemia when used with insulin. See the analogue profiles.

Community-reported

none documented for native amylin.

Theoretical. chronic exposure to aggregation-prone human amylin could in principle promote islet amyloid; this is why no native-sequence product exists. Amylin receptors overlap with calcitonin receptors — bone turnover is a theoretical consideration with long-term agonism, not confirmed as a clinical problem.

Interactions. additive slowing of gastric emptying with GLP-1 agonists; hypoglycaemia risk when combined with insulin or sulfonylureas (established for pramlintide); delayed absorption of oral medicines that need rapid onset.

Markers researchers commonly monitor

Native amylin is not administered clinically; the markers below come from amylin physiology and the analogue trials:

MarkerWhy it's watched
Fasting and post-meal plasma amylinresearch assay; low or absent in type 1 diabetes, raised with insulin resistance. Not a routine clinical test.
Post-meal glucose excursions (CGM or meal tests)the physiological readout of amylin's gastric-emptying and glucagon effects.
Post-meal glucagonsuppressed by amylin agonism.
Gastric emptying (breath test or scintigraphy)slowed by amylin and its analogues.
Body weight and appetite/nausea scoresprimary pharmacodynamic measures in analogue trials.
HbA1clong-term glycaemic effect when analogues are used in diabetes.
Calcium and bone turnover markersa reasonable research precaution given shared calcitonin-receptor signalling; no clinical signal to date.

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5Reconstitution and handling

Native human amylin is a research-grade peptide for laboratory use only. It aggregates in aqueous solution within hours at room temperature and is usually handled in hexafluoroisopropanol or freshly dissolved immediately before use in cell and animal experiments. There is no pharmaceutical presentation, no validated handling guidance for people, and no self-administered dose. The site calculator is not applicable.

6Commonly studied alongside

Pramlintide, cagrilintide (with semaglutide as CagriSema), petrelintide, eloralintide — the analogues that carry its biology into medicine; semaglutide and tirzepatide (combination partners and comparators); leptin / metreleptin (synergy studies); calcitonin and CGRP (same receptor family); PYY3-36 and oxyntomodulin (fellow satiety hormones in multi-hormone research).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

RegionStatus (checked —)
United StatesNative amylin not approved. Pramlintide (Symlin) FDA-approved for type 1 and type 2 diabetes with mealtime insulin
European UnionNative amylin not authorised; pramlintide never marketed in the EU; long-acting analogues investigational
United KingdomNot licensed; analogues investigational
AustraliaNot approved
South AfricaNot registered
SportNot specifically listed by WADA; a non-approved substance would fall under S0 †

8Open questions

  • How much of the weight loss from long-acting amylin analogues comes from brainstem satiety signalling versus slowed gastric emptying?
  • Does chronic amylin-receptor agonism carry any long-term bone or calcitonin-related effects in humans?
  • Can blocking amylin aggregation in the islet slow progression of type 2 diabetes — the pathological side of the molecule?
  • Do analogues with different AMY/calcitonin receptor balance (DACRAs) offer better tolerability than selective amylin ?

9References

  1. 1Cooper GJ et al. (1987). Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. Proc Natl Acad Sci USA. PubMed · DOI
  2. 2Westermark P, Andersson A, Westermark GT (2011). Islet amyloid polypeptide, islet amyloid, and diabetes mellitus. Physiol Rev. PubMed · DOI
  3. 3Young A (2005). Amylin: physiology and pharmacology. Adv Pharmacol (volume 52, Academic Press). PubMed
  4. 4Hay DL et al. (2015). Amylin: pharmacology, physiology, and clinical potential. Pharmacol Rev. PubMed · DOI
  5. 5Ludvik B et al. (1991). Amylin: history and overview / plasma islet amyloid polypeptide in obesity and diabetes. Diabetes. PubMed
  6. 6Roth JD et al. (2008). Leptin responsiveness restored by amylin agonism in diet-induced obesity: evidence from nonclinical and clinical studies. Proc Natl Acad Sci USA. PubMed · DOI
  7. 7Ravussin E et al. (2009). Enhanced weight loss with pramlintide/metreleptin: an integrated neurohormonal approach to obesity pharmacotherapy. Obesity. PubMed · DOI
  8. 8Lau DCW et al. (2021). 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. PubMed · DOI
  9. 9Masters SL et al. (2010). Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes. Nat Immunol. PubMed · DOI
  10. 10Zealand Pharma (2025). ZUPREME-1 Phase 2b topline results for petrelintide (company release) [verify]. PubMed
  11. 11Eli Lilly (2025). Lilly's selective amylin agonist eloralintide demonstrated meaningful weight loss and favorable tolerability in a Phase 2 study of adults with obesity or overweight (company release, November 2025). PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

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11Page history

30 Oct 2026Profile published — awaiting medical review

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