Abstract

EVIDENCE-BASED REVIEW OF SGLT2 INHIBITORS: INSIGHTS FROM CLINICAL TRIALS IN MULTISYSTEM DISEASE MANAGEMENT

Ragul Ezhumalai*, Pavithran G., Ragu Ram C. R., Sivaramaswamy N., Dharma M., Subaneshwaran S.

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Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, initially developed for glycemic control in type 2 diabetes (T2D), have emerged as a groundbreaking class of medications due to their profound and consistent cardiovascular and renal benefits. This review synthesizes the current understanding of SGLT2 inhibitors' mechanisms of action, approved agents, clinical pharmacology, and established therapeutic roles in T2D, heart failure (HF), and chronic kidney disease (CKD). Beyond their primary effect of increasing renal glucose excretion, SGLT2 inhibitors exert pleiotropic effects, including hemodynamic improvements (e.g., reduced intraglomerular pressure, plasma volume reduction), metabolic shifts (e.g., enhanced ketone body utilization), and anti-inflammatory/anti-fibrotic properties. Pivotal clinical trials have demonstrated significant reductions in cardiovascular death, hospitalization for heart failure across the ejection fraction spectrum (HFrEF and HFpEF), and progression of CKD (including end-stage kidney disease) in patients with and without T2D. While generally well-tolerated, common adverse effects include genitourinary infections and a rare risk of euglycemic diabetic ketoacidosis. The clinical pharmacist plays a vital role in patient education, drug interaction management, and monitoring parameters to optimize therapy. Future applications may extend to broader cardiorenal protection, obesity, non-alcoholic fatty liver disease, and polycystic kidney disease. SGLT2 inhibitors represent a triple threat against interconnected cardiometabolic and renal diseases, fundamentally reshaping evidence-based clinical practice and improving patient outcomes.

Keywords: SGLT2 inhibitors, Type 2 diabetes, Heart failure, Chronic kidney disease, Cardiorenal protection, Dapagliflozin, Empagliflozin, Canagliflozin, Ertugliflozin.