Intervention
SGLT2 Inhibitors (Empagliflozin, Dapagliflozin, Canagliflozin)
Last updated 2026-05-17· 1 min read
Reviewed by the Ultimate Longevity Bible editorial team. Educational reference — not medical advice. See disclaimer.
What they are
Sodium-glucose cotransporter-2 inhibitors block glucose reabsorption in the proximal renal tubule, causing glucosuria. Approved for type-2 diabetes, heart failure (regardless of diabetes), and chronic kidney disease.
Why they matter
- Mortality: empagliflozin reduced cardiovascular mortality by ~38% in T2D with established cardiovascular disease (EMPA-REG OUTCOME).
- Heart failure: large RCTs (DAPA-HF, EMPEROR) show ~25% reduction in heart-failure hospitalisation in HFrEF and HFpEF.
- Kidney disease: ~30–40% reduction in CKD progression in both diabetic and non-diabetic CKD.
- Longevity signal: canagliflozin extends male mouse lifespan in the NIA ITP.
Likely mechanisms
- Calorie loss via glucosuria (acts a bit like calorie restriction).
- Ketogenesis (mild ketosis improves cardiac fuel economy).
- Reduced glomerular hyperfiltration.
- Reduced inflammation, oxidative stress.
- Beneficial sodium handling and blood pressure.
Safety
- Genital mycotic infections (more common).
- Urinary tract infections.
- Euglycemic DKA (rare but serious, especially during illness or fasting).
- Volume depletion in frail older adults.
- Heart Failure (HFpEF / HFrEF) — Disease.
- Heart Failure with Preserved Ejection Fraction (HFpEF) — Disease.
- DAPA-HF & EMPEROR-Reduced — Trial.
- NT-proBNP (and BNP) — Biomarker.
Related entries
Cardiovascular disease, Chronic kidney disease, EMPA-REG OUTCOME, ITP.
References
- Zinman, B. et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes (EMPA-REG OUTCOME). N. Engl. J. Med. 373, 2117–2128 (2015).