A 52-year-old man with type 2 diabetes and an eGFR of 48 mL/min/1.73 m² is started on empagliflozin. The primary mechanism by which this drug reduces cardiovascular mortality (as shown in the EMPA-REG OUTCOME trial) is BEST explained by:

• A Reduction in HbA1c leading to decreased atherosclerotic plaque formation
• B Direct inhibition of myocardial SGLT1 channels reducing intracellular calcium overload
• C Stimulation of erythropoietin production improving myocardial oxygen delivery
• D Haemodynamic unloading via osmotic diuresis and natriuresis reducing cardiac preload and afterload ✓

Explanation

The EMPA-REG OUTCOME trial demonstrated a 38% reduction in CV death with empagliflozin; the predominant mechanism is haemodynamic — SGLT2 inhibition causes glucosuria-driven osmotic diuresis and natriuresis, reducing plasma volume, preload, afterload, and myocardial wall stress. The benefit was too rapid to be explained by HbA1c reduction or atherosclerosis regression. SGLT1 is primarily a myocardial and intestinal transporter, distinct from SGLT2 in the kidney.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.