Empagliflozin reduces cardiovascular mortality in patients with type 2 diabetes and established CVD (EMPA-REG OUTCOME trial). The proposed mechanism of cardiovascular benefit beyond glucose lowering involves:

• A Reduction of epicardial fat mass improving coronary perfusion
• B Lowering HbA1c by 1.5% reducing atherosclerosis progression
• C Direct inhibition of cardiac sodium-hydrogen exchanger 1 (NHE1) reducing cardiac hypertrophy ✓
• D SGLT2 inhibition in the kidney reducing podocyte loss

Explanation

Beyond glycosuria and glucose lowering, empagliflozin is thought to directly inhibit cardiac NHE1 (sodium-hydrogen exchanger type 1), reducing intracellular sodium and subsequently intracellular calcium overload in cardiomyocytes, a mechanism improving cardiac contractility and reducing hypertrophy independent of any metabolic effect. Additionally, the osmotic diuresis and natriuresis reduce preload and afterload. This direct cardiac effect is a leading explanation for the rapid (within weeks) onset of cardiovascular benefit seen in EMPA-REG.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.