SGLT2 inhibitors (empagliflozin, dapagliflozin) reduce cardiovascular mortality in type 2 diabetes independent of glycemic control. The primary mechanism responsible for their cardioprotective effect is thought to be:
- A Reduction of HbA1c and lowering of oxidative stress from hyperglycemia
- B Osmotic diuresis and natriuresis reducing preload and afterload, with possible direct myocardial metabolic benefits ✓
- C GLP-1 receptor agonism increasing cardiac myocyte energy efficiency
- D Beta-2 adrenergic stimulation increasing myocardial contractility
Explanation
SGLT2 inhibitors work by glucosuria and natriuresis (sodium-glucose cotransport inhibition in the proximal tubule), reducing plasma volume and preload. Sustained natriuresis reduces afterload. Additional proposed mechanisms include switching myocardial energy metabolism from glucose to ketones (more oxygen-efficient), reducing sympathetic activity via afferent renal denervation, and direct anti-fibrotic effects. These collectively reduce hospitalizations for heart failure and cardiovascular death. These effects are independent of glucose-lowering. GLP-1 agonism is the mechanism of GLP-1 receptor agonists (option C).
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.