Vascular pharmacologyDec 4, 2025

Targeting amylin receptors with new peptide treatments for obesity

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Jan 20, 2026

Abstract

Amylin receptor agonists (AMYRAs) may offer advantages over existing weight loss medications.

Obesity is characterized by an imbalance in energy regulation influenced by genetic and environmental factors.
GLP-1 receptor agonists have shown mild weight loss but face challenges with efficacy and tolerability.
Amylin, co-released with insulin, regulates hunger and energy metabolism through different receptor subtypes.
Emerging data suggest that peptide-based AMYRAs, such as pramlintide and cagrilintide, may enhance weight regulation.
Novel delivery methods and combination therapies with digital health technologies and bariatric surgery are explored.
While AMYRAs are associated with potential benefits for weight management, their definitive effects on disease modification are still uncertain.

Simplified

Obesity is a chronic, relapsing metabolic disorder driven by complex genetic and environmental factors, leading to an imbalance in energy regulation. Despite the presence of GLP-1 receptor agonists with induced mild weight loss, there are significant unmet clinical needs with poor efficacy and tolerability problems. Amylin, a neuroendocrine hormone co-released with insulin, controls hunger, gastric motility, glucagon secretion, and energy metabolism via divergent amylin receptor (AMYR) subtypes (1-3), namely the calcitonin receptor (CTR) and the receptor activity-modifying proteins (RAMPs). Novel insight into the molecular make-up of AMYRs and central signaling reinforces its key function in modulating homeostatic and hedonic feeding mechanisms. The article is a review of the emerging preclinical and clinical data regarding the application of peptide-based amylin receptor agonists (AMYRAs), including pramlintide and cagrilintide, KBP-series DACRAs, and investigational drugs, including ZP8396 and amycretin. The agents show enhanced pharmacokinetics, synergy with GLP-1 receptor agonist, and favorable impact on weight regulation and metabolic plasticity. Genetic CALCR and RAMP mutations, new delivery approaches, and dual therapy by digital health technologies and bariatric surgery are also discussed in this review. Of particular interest, amylin-derived medications can have advantages over weight loss but definite disease-modifying action remains to be determined. Taken together, AMYRAs represent a potential category of therapeutics with promising disease-modifying effects that goes beyond weight loss, providing fresh perspectives for precision obesity management by 2030.

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Targeting amylin receptors with new peptide treatments for obesity

Abstract

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Competing interests

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Abstract

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