Abstract
The identification of amylin as a glucoregulatory peptide hormone with roles in meal-ending satiation sparked a surge of experimental development, which culminated in the amylin mimetic drug pramlintide. Pramlintide was approved by the FDA in 2005 for the treatment of type 1 diabetes mellitus and insulin-requiring type 2 diabetes, and was also explored as a novel anti-obesity treatment. Despite this exciting potential, efforts to develop an amylin-based anti-obesity therapeutic stalled owing to challenges around dosage frequency, safety and formulation. Generally, anti-obesity therapies have displayed modest efficacy and mixed safety profiles, leaving a clear unmet clinical need that requires addressing. Advances in peptide chemistry have reinvigorated the amylin field by enabling the manufacture of effective new amylin-based molecules, resulting in therapeutics that are now on the cusp of approval. At present, there are growing concerns around GLP1 receptor agonist-based therapeutics, in particular their association with loss of lean body mass. Additionally, treatment of patients with overweight or obesity without associated comorbidities is increasingly common. The widespread pharmacotherapy of otherwise healthy populations with overweight or obesity with the goal of improving future health requires further regulatory and ethical consideration. This Review describes how amylin controls energy homeostasis and provides a current overview of amylin-based therapeutic development.
Key points
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Amylin is a neuroendocrine peptide hormone, biosynthesized mainly in the pancreatic islet β-cells and co-secreted with insulin, that circulates in the blood and controls food intake, glucose homeostasis and energy metabolism.
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There are at least three amylin receptors, AMY1, AMY2 and AMY3, each of which is composed of the calcitonin receptor bound to one of three corresponding receptor activity-modifying proteins.
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Amylin acts as a natural satiety signal that suppresses appetite, delays gastric emptying and reduces food intake by activating specific amylin receptors present in many regions of the brain.
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Treatment with amylin mimetics induces weight loss in humans and rodent models.
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Amylin receptors are considered proven drug targets and amylin mimetics are emerging as novel treatments for overweight, obesity and diabetes mellitus.
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The authors acknowledge funding support from the New Zealand Ministry of Business, Innovation & Employment Hīkina Whakatutuki (UOAX1809; UOA24102).
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Walker, C.S., Aitken, J.F., Vazhoor Amarsingh, G. et al. Amylin: emergent therapeutic opportunities in overweight, obesity and diabetes mellitus. Nat Rev Endocrinol (2025). https://doi.org/10.1038/s41574-025-01125-9
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DOI: https://doi.org/10.1038/s41574-025-01125-9
