SGLT-2 inhibitors (gliflozins) reduce HbA1c by glucosuria but also confer cardiovascular and renal benefits independent of glycaemic control. The primary mechanism of their cardiorenal protection involves:
- A Reduction of tubuloglomerular feedback via decreased proximal sodium-glucose reabsorption ✓
- B Activation of GLP-1 receptors on cardiac myocytes
- C Direct beta-1 adrenoceptor antagonism reducing heart rate
- D Inhibition of DPP-4 preserving endogenous incretin levels
Explanation
SGLT-2 inhibitors block sodium-glucose co-transporter 2 in the proximal tubule, reducing glucose AND sodium reabsorption. Increased distal sodium delivery to the macula densa restores tubuloglomerular feedback, causing afferent arteriolar vasoconstriction, reducing intraglomerular hypertension and GFR hyperfiltration — the key mechanism of renal protection (CREDENCE/DAPA-CKD). The reduced plasma volume and osmotic diuresis also reduce cardiac preload. GLP-1 receptor activation is the mechanism of GLP-1 receptor agonists; DPP-4 inhibition is the mechanism of gliptins.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.