Amylin, a neuroendocrine hormone co-secreted with insulin from pancreatic β-cells, plays a crucial role in glucose homeostasis, satiety, and body weight regulation. It inhibits postprandial glucagon secretion, slows gastric emptying, and reduces appetite. Amylin and its analogs, pramlintide and cagrilintide, are being explored for their therapeutic potential in treating diabesity, a condition linking type 2 diabetes mellitus (T2DM) and obesity. Amylin acts through various mechanisms, including the activation of amylin receptors, which are structurally related to calcitonin receptors. These receptors are complex, involving combinations of calcitonin receptor (CTR) and receptor activity-modifying proteins (RAMP). Amylin analogs have shown efficacy in reducing postprandial glucose excursions, improving glycemic control, and promoting weight loss. Pramlintide, a synthetic amylin analog, is used in both T1DM and T2DM to manage postprandial hyperglycemia and is administered subcutaneously. It has a short half-life and is effective in reducing HbA1c levels and body weight. Cagrilintide, a long-acting amylin analog, is also being studied for its potential in treating obesity and T2DM. Both pramlintide and cagrilintide have shown safety and efficacy in clinical trials, with pramlintide being particularly effective in T2DM patients. Ongoing research aims to further elucidate the clinical pharmacology and therapeutic potential of amylin and its analogs in the treatment of diabesity. The combination of cagrilintide and semaglutide (CagriSema) is being tested for its potential in managing diabesity. Overall, amylin and its analogs represent promising therapeutic options for the treatment of diabesity, with further studies expected to provide more insights into their mechanisms and applications.Amylin, a neuroendocrine hormone co-secreted with insulin from pancreatic β-cells, plays a crucial role in glucose homeostasis, satiety, and body weight regulation. It inhibits postprandial glucagon secretion, slows gastric emptying, and reduces appetite. Amylin and its analogs, pramlintide and cagrilintide, are being explored for their therapeutic potential in treating diabesity, a condition linking type 2 diabetes mellitus (T2DM) and obesity. Amylin acts through various mechanisms, including the activation of amylin receptors, which are structurally related to calcitonin receptors. These receptors are complex, involving combinations of calcitonin receptor (CTR) and receptor activity-modifying proteins (RAMP). Amylin analogs have shown efficacy in reducing postprandial glucose excursions, improving glycemic control, and promoting weight loss. Pramlintide, a synthetic amylin analog, is used in both T1DM and T2DM to manage postprandial hyperglycemia and is administered subcutaneously. It has a short half-life and is effective in reducing HbA1c levels and body weight. Cagrilintide, a long-acting amylin analog, is also being studied for its potential in treating obesity and T2DM. Both pramlintide and cagrilintide have shown safety and efficacy in clinical trials, with pramlintide being particularly effective in T2DM patients. Ongoing research aims to further elucidate the clinical pharmacology and therapeutic potential of amylin and its analogs in the treatment of diabesity. The combination of cagrilintide and semaglutide (CagriSema) is being tested for its potential in managing diabesity. Overall, amylin and its analogs represent promising therapeutic options for the treatment of diabesity, with further studies expected to provide more insights into their mechanisms and applications.