Sglt2 receptor what is what sglt2 inhibitors
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SGLT2 receptor sodium glucose cotransporter 2 mechanism physiology kidney
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SGLT2 inhibitors drugs clinical use diabetes heart failure renal protection
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SGLT2 Receptor & SGLT2 Inhibitors
What is SGLT2?
Sodium-Glucose Cotransporter 2 (SGLT2) is a transport protein located in the proximal convoluted tubule of the kidney. Its role is to reabsorb glucose from the glomerular filtrate back into the bloodstream by co-transporting it with sodium.
- The kidneys normally filter ~180g of glucose per day
- Under normal conditions, virtually all of this glucose is reabsorbed — mainly via SGLT2 (~90%) and SGLT1 (~10%)
- SGLT2 is a low-affinity, high-capacity transporter — it handles the bulk of glucose reabsorption
- It is encoded by the SLC5A2 gene and is expressed almost exclusively in the kidney
What are SGLT2 Inhibitors?
SGLT2 inhibitors (also called gliflozins) are a class of oral medications that block the SGLT2 transporter, preventing glucose reabsorption. This causes excess glucose to be excreted in the urine (glucosuria), lowering blood sugar levels.
Common SGLT2 Inhibitors
| Drug | Brand Name | Notes |
|---|---|---|
| Empagliflozin | Jardiance | Major CV benefit (EMPA-REG trial) |
| Dapagliflozin | Farxiga / Forxiga | CV + renal benefit (DAPA-HF, DAPA-CKD) |
| Canagliflozin | Invokana | CV benefit (CANVAS trial) |
| Ertugliflozin | Steglatro | Newer agent |
Mechanisms & Effects
| Effect | Mechanism |
|---|---|
| Lower blood glucose | Blocks SGLT2 → glucosuria (~70–90g glucose/day excreted) |
| Weight loss | Caloric loss via urine |
| Lower blood pressure | Tubuloglomerular feedback → osmotic diuresis; reduces systolic BP by 3–6 mmHg |
| Lower serum urate | ~10% reduction (mild uricosuric effect) |
| Renal protection | Reduces intraglomerular pressure via tubuloglomerular feedback |
| Heart failure benefit | Diuresis + reduced preload/afterload |
Clinical Indications
- Type 2 Diabetes — as monotherapy or add-on (with metformin, sulfonylureas, insulin)
- Heart Failure (HFrEF and HFpEF) — dapagliflozin and empagliflozin are approved regardless of diabetes status
- Chronic Kidney Disease (CKD) — dapagliflozin shown to slow progression
- Cardiovascular risk reduction — especially in patients with established CV disease
Side Effects
| Side Effect | Details |
|---|---|
| Genitourinary infections | Most common — vaginal candidiasis, UTIs (due to glucosuria) |
| Dehydration / Dizziness | Osmotic diuresis; prevent with adequate fluid intake |
| Diabetic ketoacidosis (DKA) | Rare in T2DM; risk higher if insulin withheld (euglycemic DKA) |
| Fournier's gangrene | Rare but serious necrotizing perineal infection |
| Lower limb amputation | Noted with canagliflozin (CANVAS trial) |
| Fractures | Signal seen with canagliflozin |
Important Considerations
- Avoid with loop diuretics — additive diuretic effect increases dehydration risk
- Diminished efficacy in renal impairment — SGLT2 expression decreases as GFR falls; glucose-lowering effect is lost at eGFR <45 mL/min (though renal/cardiac protective effects may persist at lower eGFR for some agents)
- Hold before surgery — withhold 3–4 days prior to prevent euglycemic DKA
Sources: Type 2 Diabetes Glycaemic Management Algorithm (p. 7); supplemented from current pharmacology and cardiology/nephrology guidelines.
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