Canagliflozin — The SGLT2 Inhibitor for Metabolic Health
Canagliflozin is an SGLT2 inhibitor originally developed for type 2 diabetes that has gained attention for its lifespan-extending properties in animal models. By promoting glucose excretion and mimicking a fasting state, it activates key longevity pathways like AMPK while suppressing mTOR.
Mechanism of Action
Canagliflozin inhibits the sodium-glucose cotransporter 2 (SGLT2) in the proximal renal tubules, reducing glucose reabsorption and increasing urinary glucose excretion. This induces a fasting-like metabolic state, lowering insulin levels and activating AMPK. Consequently, mTORC1 signaling is suppressed, promoting cellular repair processes like autophagy. It has also been shown to reduce senescent cell burden in preclinical models.
Human Trial Evidence
No published human longevity trials. Animal/in-vitro evidence only. However, large-scale cardiovascular outcome trials in diabetic patients show significant reductions in heart failure and kidney disease progression.
Dosing Protocol
100 mg daily or 150 mg every 48 hours is commonly used in off-label longevity protocols. In clinical practice for diabetes, doses range from 100 to 300 mg daily. Requires a prescription.
Safety & Contraindications
Common adverse effects include urinary tract infections, genital mycotic infections, and increased urination. Rare but serious risks include euglycemic diabetic ketoacidosis, lower limb amputation, and Fournier's gangrene. Contraindicated in severe renal impairment and dialysis patients. Requires a prescription.