SGLT2 Inhibitors: A Novel Therapeutic Class for Diabetes Management

Abstract

This narrative review aims to analyze the efficacy, safety, and evolving roles of sodium-glucose cotransporter-2 (SGLT2) inhibitors in managing diabetes mellitus, focusing on their mechanisms of action, clinical benefits, cost-effectiveness, and extra-glycemic effects. SGLT2 inhibitors represent a groundbreaking advancement in treating type 2 diabetes, particularly in patients with cardiovascular risk factors. Despite the widespread use of metformin as first-line therapy and other antihyperglycemic agents, many patients fail to achieve optimal glycemic control, highlighting the need for additional treatment options. SGLT2 inhibitors, including empagliflozin, canagliflozin, and dapagliflozin, significantly reduce hemoglobin A1c levels by 0.5-1.0%, while also promoting weight loss and reducing blood pressure. These substantial metabolic improvements are associated with a significant decrease in major adverse cardiovascular events, heart failure hospitalizations, and renal disease progression. The mechanism of action involves inhibiting glucose reabsorption in the proximal tubule of the kidney, thereby enhancing urinary glucose excretion. Beyond their glucose-lowering effects, SGLT2 inhibitors offer additional metabolic benefits, including reduced inflammation, improved endothelial function, and favorable effects on lipid metabolism, factors that collectively contribute to lowering cardiovascular risk. Clinical trials have consistently demonstrated the safety and efficacy of SGLT2 inhibitors, with common adverse effects being mild genitourinary infections and no significant increase in hypoglycemia risk when used as monotherapy. However, the relatively high cost of SGLT2 inhibitors presents a significant barrier to their widespread adoption, limiting their cost-effectiveness, especially in patients without established cardiovascular disease. Emerging research also suggests potential roles for SGLT2 inhibitors in treating conditions beyond diabetes, such as heart failure with preserved ejection fraction and chronic kidney disease.