What is the amylin receptor?

What the research literature says

The amylin-receptor complex is unusual among GPCRs in being formed by heterodimerisation rather than as a single dedicated receptor protein. The calcitonin receptor on its own is the high-affinity receptor for calcitonin; when calcitonin receptor associates with RAMP1, RAMP2, or RAMP3, the complex’s affinity profile shifts to favour amylin binding. The three RAMP isoforms produce three distinct amylin-receptor subtypes (AMY1, AMY2, AMY3) with different tissue distribution and pharmacology.

Cagrilintide is the synthetic long-acting amylin analogue characterised in the Kruse development paper (PMID 34288673). The Lau phase 2 dose-finding trial established the weight-management efficacy framework for cagrilintide monotherapy (PMID 34798060). The combined-formulation the cagrilintide-and-semaglutide combination (cagrilintide + semaglutide) was characterised in the Enebo phase 1b trial (PMID 33894838) and the Frias type 2 diabetes phase 2 trial (PMID 37364590).

Amylin-receptor pharmacology produces gastric-emptying-slowing, glucagon-suppression, and centrally-mediated satiety effects — actions complementary to insulin (which is co-secreted with amylin from pancreatic beta cells) but operating on different time courses and through different receptor pathways.

Why this matters in research context

The amylin receptor matters in peptide-research contexts as the second pharmacological arm of the cagrilintide-and-semaglutide combination. Researchers studying combined-mechanism weight-management approaches via the amylin + GLP-1 strategy should anchor protocol design to the dual-receptor framework; the amylin-receptor pharmacology is distinct from the incretin-receptor (GLP-1, GIP, glucagon) pharmacology that dominates the other long-acting peptide-therapeutic class.

Related compounds

Related research questions

• What is amylin?

References

1. Enebo LB 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]
2. Kruse T et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem 2021;64(15):11183-11194. [PMID 34288673]
3. Lau DCW 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]
4. Frias JP 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. Lancet 2023;402(10403):720-730. [PMID 37364590]