Ultimate Longevity Bible

Intervention

SGLT2 Inhibitors (Empagliflozin, Dapagliflozin, Canagliflozin)

Last updated Sun May 17 2026 00:00:00 GMT+0000 (Coordinated Universal Time)

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.

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).

More interventions