====== SGLT2 Inhibitors (Gliflozins) ====== SGLT2 inhibitors are sodium-glucose cotransporter-2 inhibitors that act in the proximal tubule of the kidney. Originally developed for Type 2 Diabetes, they are now foundational therapies in: • [[cardio:heart_failure:start|Heart Failure]] • Chronic Kidney Disease • Type 2 Diabetes Mellitus Their cardiovascular and renal benefits extend beyond glucose lowering. -------------------------------------------------------------------- ===== Mechanism of Action ===== Location: • Proximal convoluted tubule Normal physiology: • SGLT2 reabsorbs ~90% of filtered glucose • Sodium and glucose are co-transported Drug effect: • Blocks SGLT2 • Increases urinary glucose excretion • Causes mild natriuresis • Reduces intraglomerular pressure Net physiologic effects: • ↓ Blood glucose • Mild osmotic diuresis • ↓ Preload • ↓ Blood pressure • ↓ Cardiorenal stress -------------------------------------------------------------------- ===== Available Agents ===== * • [[endocrine:sglt2:dapagliflozin|Dapagliflozin]] * • [[endocrine:sglt2:empagliflozin|Empagliflozin]] * • [[endocrine:sglt2:sotagliflozin|Sotagliflozin]] All share similar cardiorenal benefits. -------------------------------------------------------------------- ===== Indications ===== ==== Type 2 Diabetes Mellitus ==== • Improve glycemic control • Promote modest weight loss • Reduce cardiovascular events -------------------------------------------------------------------- ==== Heart Failure ★ ==== Indicated for: • HFrEF • HFpEF Benefits: • ↓ Heart failure hospitalization • ↓ Cardiovascular mortality • Effective regardless of diabetes status Part of the Four Pillars in HFrEF. → [[cardio:heart_failure:start|Heart Failure Module]] -------------------------------------------------------------------- ==== Chronic Kidney Disease ==== • Slows progression of CKD • Reduces albuminuria • Preserves GFR Renal benefit independent of diabetes. -------------------------------------------------------------------- ===== Adverse Effects ===== Common: • Genital mycotic infections • Polyuria • Volume depletion • Hypotension Serious (rare): • Euglycemic DKA • Fournier gangrene -------------------------------------------------------------------- ===== Contraindications / Cautions ===== • Type 1 diabetes (DKA risk) • Severe volume depletion • Advanced renal impairment (varies by agent) Hold during acute illness or prolonged fasting. -------------------------------------------------------------------- ===== SGLT2 vs Other Metabolic Agents ===== Compared to: • [[endocrine:glp1:start|GLP-1 Receptor Agonists]] SGLT2 inhibitors: * • Strong heart failure benefit * • Strong renal protection * • Mild diuretic effect GLP-1 receptor agonists: * • Greater weight loss * • Stronger atherosclerotic benefit -------------------------------------------------------------------- ===== Clinical Pearls ===== ✔ Act in the proximal tubule ✔ Mild diuretic effect ✔ Reduce HF hospitalization ✔ Slow CKD progression ✔ Benefit independent of diabetes status ✔ One of the Four Pillars of HFrEF -------------------------------------------------------------------- Related: → [[cardio:heart_failure:start|Heart Failure Module]] → [[cardio:intro:start|Cardiovascular Modules]] → [[endocrine:start|Endocrine Pharmacology]]