SGLT2 inhibitors started as diabetes drugs. Outcome trial data showing 25–35% reductions in cardiovascular death and a 14% lifespan extension in male mice has pushed them into longevity discussions. Here's the complete picture.
SGLT2 inhibitors are the newest entry in the longevity drug conversation. Bryan Johnson added Jardiance (empagliflozin) and Brenzavvy (bexagliflozin) to the Immortals Rx platform. Peter Attia has discussed empagliflozin at length. The NIA Interventions Testing Program found that canagliflozin (same class) extended lifespan in male mice by 14% — one of the largest effects seen in the ITP's rigorous multi-site protocol.
This article explains what SGLT2 inhibitors do, what the human outcome trial data shows, and how to think about the risk-benefit calculation for non-diabetic longevity use.
SGLT2 (sodium-glucose cotransporter 2) is a protein in the kidney proximal tubule that reabsorbs ~90% of filtered glucose back into the bloodstream. SGLT2 inhibitors block this reabsorber, causing the kidneys to excrete 50–100g of glucose per day in the urine regardless of diet or insulin levels. The downstream effects:
Glucose and insulin: Fasting glucose falls 15–25 mg/dL; HbA1c falls 0.5–1.0%. Crucially, because the mechanism is insulin-independent, the drugs lower glucose without causing hypoglycemia.
Weight: Caloric loss from glycosuria causes 2–4 kg of weight loss over 6 months. The effect plateaus as the body adapts.