Management of Diabetes Mellitus: The Role of Alpha-Amylase and Alpha-Glucosidase Enzymes

Diabetes mellitus is a chronic, progressive metabolic disorder characterized by persistent hyperglycemia arising from defects in insulin secretion, insulin action, or both. According to the International Diabetes Federation, an estimated 462 million individuals worldwide were affected by type 2 diabetes mellitus (T2DM) in 2017, representing 6.28% of the global population; this prevalence is projected to rise to 7,079 cases per 100,000 by 2030. The pathophysiology of diabetes involves a constellation of genetic, environmental, and lifestyle factors that culminate in metabolic dysregulation affecting carbohydrate, protein, and lipid homeostasis. Among the therapeutic targets for glycemic control, the carbohydrate-digesting enzymes α-amylase (EC 3.2.1.1) and α-glucosidase (EC 3.2.1.20) play pivotal roles in regulating postprandial glucose absorption. Pharmacological inhibition of these enzymes has emerged as a mechanistically rational strategy to delay carbohydrate breakdown and attenuate postprandial hyperglycemia — a major contributor to both microvascular and macrovascular diabetic complications. α-Amylase catalyzes the hydrolysis of internal α-1,4-glycosidic bonds in starch, while α-glucosidase hydrolyzes terminal bonds of oligosaccharides into absorbable monosaccharides. This review provides an in-depth synthesis of the physiological functions and biochemical mechanisms of these enzymes, the molecular basis of synthetic and plant-derived inhibitors, and the clinical-trial evidence base supporting enzyme-inhibitor therapy. Emphasis is placed on quantitative structure–activity relationships, recent randomized cardiovascular outcome trials, and emerging nanocarrier-based delivery platforms.