Incretin Hormones: Mechanisms, Therapeutic Implications, and Future Directions in Glucose Regulation and Diabetes Management

Type 2 diabetes (T2D) is a global health crisis, currently affecting over 540 million individuals. Its prevalence continues to rise due to aging populations, sedentary lifestyles, and unhealthy diets. T2D accounts for approximately 90–95% of all diabetes cases and is a leading cause of cardiovascular and metabolic morbidity. Incretin hormones—glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)—play essential roles in glucose homeostasis, insulin secretion, and metabolic regulation. Their dysfunction significantly contributes to the pathophysiology of T2D. This review aims to provide an updated synthesis of incretin hormone biology, emphasizing GLP-1 and GIP mechanisms in glucose regulation, β-cell function, and their therapeutic potential in T2D. Relevant studies from 2000 to 2024 were reviewed from databases including PubMed and Scopus, focusing on incretin physiology, receptor signaling, therapeutic applications, and mechanisms of secretion. GLP-1 and GIP stimulate glucose-dependent insulin release, reduce glucagon levels, delay gastric emptying, and contribute to satiety and cardiovascular benefits. Incretin-based therapies—including GLP-1 receptor agonists and DPP-4 inhibitors—demonstrate significant benefits in glycemic control, though limitations such as β-cell resistance and modest cardiovascular outcomes in some agents persist. Dual receptor agonists like tirzepatide show improved metabolic effects. Recent insights into nutrient sensing pathways and enteroendocrine activation offer promising therapeutic directions. Advancements in incretin therapy have transformed T2D treatment. Future strategies should target β-cell resistance, leverage dual agonists, personalize therapies, and develop pharmacologic methods to mimic the hormonal profile of bariatric surgery.