SGLT2 Inhibitors

These diabetes drugs lower glucose by flushing it through the kidneys — but that sugar-rich urine creates a perfect breeding ground for infections you need to anticipate.

SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin — all end in "-gliflozin") work by blocking the sodium-glucose cotransporter 2 in the proximal convoluted tubule of the kidney. Normally, SGLT2 reabsorbs about 90% of filtered glucose back into the blood. Blocking it causes glycosuria — the patient literally urinates out excess glucose. This mechanism is insulin-independent, meaning it works regardless of beta-cell function or insulin resistance. Beyond glucose lowering, SGLT2 inhibitors provide proven cardiovascular and renal protection: empagliflozin and dapagliflozin reduce heart failure hospitalizations and slow progression of chronic kidney disease, making them first-line add-ons for patients with type 2 diabetes and HFrEF or CKD. Because the mechanism is renal, efficacy decreases as GFR declines — most agents require eGFR ≥ 20-25 mL/min for initiation depending on indication. A1C reduction is modest (0.5–0.8%), but the cardiorenal benefits often drive prescribing.

Key Distinctions

Don't confuse SGLT2 inhibitors with sulfonylureas — SGLT2 inhibitors carry minimal hypoglycemia risk because they don't stimulate insulin secretion. Students commonly miss euglycemic diabetic ketoacidosis (euDKA): the patient presents with DKA symptoms but a near-normal blood glucose, which delays recognition. Unlike GLP-1 agonists (injectable, GI-heavy side effects), SGLT2 inhibitors are oral and their hallmark adverse effects are genitourinary — yeast infections and UTIs from glucose-laden urine.

Clinical Pearl

Think "pee out the sugar." Gliflozin = glycosuria. Teach patients that genital itching or burning on urination isn't just annoying — it's predictable and reportable.