Diabetes mellitus, particularly type 2 diabetes (T2DM), is a significant chronic metabolic disease affecting millions globally. The gut-brain axis plays a crucial role in maintaining glucose and energy homeostasis, involving various peptides. Amylin, a neuroendocrine anorexigenic polypeptide co-secreted with insulin from pancreatic β-cells, has emerged as a potential therapeutic target for managing T2DM and obesity. This review summarizes the current evidence and ongoing studies on amylin and its analogs, pramlintide and cagrilintide, in the field of diabetology, endocrinology, and metabolism disorders. Amylin is a 37-amino-acid peptide that shares structural similarities with calcitonin gene-related peptides (CGRP) and is structurally related to calcitonin. It is synthesized as a preprohormone and undergoes cleavage to form pro-amylin, which is then amidated and forms disulfide bonds. Amylin is released in response to food consumption and has a short half-life in the plasma. Its primary functions include inhibiting postprandial glucagon secretion, slowing gastric emptying, and inducing satiety. Amylin also affects energy expenditure and body weight, making it a promising therapeutic target for managing obesity and T2DM. Pramlintide, a synthetic amylin analog, is available for both T1DM and T2DM patients. It is administered subcutaneously during mealtime and modulates postprandial glucose levels by suppressing glucagon secretion, inhibiting gastric emptying, and promoting satiety. Pramlintide is used in combination with insulin to manage postprandial hyperglycemia and has shown efficacy in reducing HbA1c levels and body weight. However, it may cause gastrointestinal symptoms such as nausea, vomiting, and anorexia. Cagrilintide, a stable lipidated non-selective long-acting amylin analog, is another promising drug under investigation. It is administered subcutaneously weekly and has demonstrated greater efficiency in treating obesity and controlling fasting glucose and HbA1c levels compared to amylin therapy. Cagrilintide is a dual amylin and calcitonin receptor agonist (DACRA) and has shown potential in combination therapies, such as CagriSema (cagrilintide + semaglutide), which has shown significant improvements in glycemic control and weight loss in clinical trials. Overall, the evidence suggests that both pramlintide and cagrilintide are safe and effective in reducing body weight and regulating glucose homeostasis in patients with T2DM. Further research is needed to fully understand their clinical pharmacology and therapeutic potentials.Diabetes mellitus, particularly type 2 diabetes (T2DM), is a significant chronic metabolic disease affecting millions globally. The gut-brain axis plays a crucial role in maintaining glucose and energy homeostasis, involving various peptides. Amylin, a neuroendocrine anorexigenic polypeptide co-secreted with insulin from pancreatic β-cells, has emerged as a potential therapeutic target for managing T2DM and obesity. This review summarizes the current evidence and ongoing studies on amylin and its analogs, pramlintide and cagrilintide, in the field of diabetology, endocrinology, and metabolism disorders. Amylin is a 37-amino-acid peptide that shares structural similarities with calcitonin gene-related peptides (CGRP) and is structurally related to calcitonin. It is synthesized as a preprohormone and undergoes cleavage to form pro-amylin, which is then amidated and forms disulfide bonds. Amylin is released in response to food consumption and has a short half-life in the plasma. Its primary functions include inhibiting postprandial glucagon secretion, slowing gastric emptying, and inducing satiety. Amylin also affects energy expenditure and body weight, making it a promising therapeutic target for managing obesity and T2DM. Pramlintide, a synthetic amylin analog, is available for both T1DM and T2DM patients. It is administered subcutaneously during mealtime and modulates postprandial glucose levels by suppressing glucagon secretion, inhibiting gastric emptying, and promoting satiety. Pramlintide is used in combination with insulin to manage postprandial hyperglycemia and has shown efficacy in reducing HbA1c levels and body weight. However, it may cause gastrointestinal symptoms such as nausea, vomiting, and anorexia. Cagrilintide, a stable lipidated non-selective long-acting amylin analog, is another promising drug under investigation. It is administered subcutaneously weekly and has demonstrated greater efficiency in treating obesity and controlling fasting glucose and HbA1c levels compared to amylin therapy. Cagrilintide is a dual amylin and calcitonin receptor agonist (DACRA) and has shown potential in combination therapies, such as CagriSema (cagrilintide + semaglutide), which has shown significant improvements in glycemic control and weight loss in clinical trials. Overall, the evidence suggests that both pramlintide and cagrilintide are safe and effective in reducing body weight and regulating glucose homeostasis in patients with T2DM. Further research is needed to fully understand their clinical pharmacology and therapeutic potentials.