A 38-year-old woman with type 2 diabetes is started on empagliflozin. The EMPA-REG OUTCOME trial demonstrated that empagliflozin's cardiovascular benefit in diabetic patients with established CVD was primarily driven by which mechanism?
- A Reduction in atherosclerotic plaque progression via SGLT2-dependent lipid lowering
- B Osmotic diuresis leading to reduction in cardiac preload and afterload (haemodynamic effect) ✓
- C Direct anti-inflammatory effect on coronary endothelium via SGLT2 receptor signalling
- D Increased glucagon secretion reducing hepatic lipogenesis
Correct answer: B. Osmotic diuresis leading to reduction in cardiac preload and afterload (haemodynamic effect)
Explanation
The EMPA-REG OUTCOME trial showed that the early and steep separation of CV mortality curves (within weeks) strongly favours a haemodynamic rather than an atherosclerotic mechanism. SGLT2 inhibition causes glycosuria and natriuresis, reducing preload (plasma volume contraction) and afterload, which is particularly beneficial in heart failure with preserved and reduced ejection fraction. Options A and C are not the primary validated mechanisms; option D is incorrect as SGLT2 inhibitors increase glucagon but this does not account for CV benefit.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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