Amylin receptors as therapeutic targets in obesity: Emerging peptide-based strategies
- Vascul Pharmacol. 2026 Mar:162:107563. doi: 10.1016/j.vph.2025.107563.
- 1. Department of Biology, College of Sciences, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
- 2. Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, Uttarakhand 248007, India. Electronic address: [email protected].
- 3. Institute of Biotechnology and Genetic Engineering (Health Division), The University of Agriculture, Peshawar 25000, Khyber Pakhtunkhwa, Pakistan.
- 4. Department of Chemistry and Biochemistry, School of Sciences, JAIN (Deemed to be University), Bangalore, Karnataka, 560069, India.
- 5. Department of General Medicine, IMS and SUM Hospital, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar, Odisha 751003, India.
- 6. Department of Chemistry, Sathyabama Institute of Science and Technology, Chennai, Tamil Nadu 600119, India.
- 7. University institute of Pharma Sciences, Chandigarh University, Mohali, Punjab 140413, India.
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.