Rankings / Longevity — Supplements
SGLT2 inhibitors (canagliflozin / empagliflozin / dapagliflozin)
Longevity · SGLT2 inhibitor / glucoretic
Also known as: Invokana ·Jardiance ·Farxiga ·gliflozin ·flozin ·empagliflozin ·dapagliflozin ·canagliflozin
Tier C+
Bottom line
Read Off Label grades SGLT2 inhibitors (canagliflozin / empagliflozin / dapagliflozin) as C+ (5.5/10) based on moderate evidence, med benefit magnitude, and a med-risk safety profile.
The strongest repurposed-drug geroscience case after rapamycin and metformin.
Typical use: Oral once daily (empagliflozin 10-25 mg, dapagliflozin 10 mg, canagliflozin 100-300 mg) — Rx.
What this is
The strongest repurposed-drug geroscience case after rapamycin and metformin. NIA Interventions Testing Program: canagliflozin extended median male-mouse lifespan ~14% (males only; Miller et al., JCI Insight 2020). Katsuumi (Nature Aging 2024): canagliflozin works as an indirect senolytic — clearing senescent cells by restoring immune surveillance — and extended lifespan in progeroid mice even when started in middle age. In humans, SGLT2 inhibitors cut all-cause mortality and heart-failure/kidney events across DECLARE-TIMI 58, EMPA-REG OUTCOME, DAPA-HF and the CKD trials, including in the very old (AGING-HF, mean age 90: mortality HR 0.67). The healthy-longevity benefit is extrapolated from disease populations and mice — no healthspan RCT yet; the male-only mouse lifespan effect is unexplained.
Mechanism
Block sodium-glucose cotransporter 2 in the kidney's proximal tubule, spilling glucose into urine; beyond glucose-lowering they shift fuel use toward ketones, lower inflammation, and act as an indirect senolytic — enhancing immune clearance of senescent cells
Dose & route
Oral once daily (empagliflozin 10-25 mg, dapagliflozin 10 mg, canagliflozin 100-300 mg)
Citations
- https://doi.org/10.1038/s43587-024-00642-y
- https://doi.org/10.1056/NEJMoa1812389
- https://doi.org/10.1161/CIRCHEARTFAILURE.125.012794
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Common questions
- Does SGLT2 inhibitors (canagliflozin / empagliflozin / dapagliflozin) work?
- Read Off Label rates the evidence for SGLT2 inhibitors (canagliflozin / empagliflozin / dapagliflozin) as Moderate and the benefit magnitude as med, producing an overall grade of C+ (5.5/10). The strongest repurposed-drug geroscience case after rapamycin and metformin.
- Is SGLT2 inhibitors (canagliflozin / empagliflozin / dapagliflozin) safe?
- SGLT2 inhibitors (canagliflozin / empagliflozin / dapagliflozin) has a med risk profile in published human data. Legal status: Rx (FDA-approved for T2D, heart failure, CKD — Invokana / Jardiance / Farxiga; off-label as a geroprotector). This is not medical advice — see the disclaimer.
- What is the typical dose for SGLT2 inhibitors (canagliflozin / empagliflozin / dapagliflozin)?
- Oral once daily (empagliflozin 10-25 mg, dapagliflozin 10 mg, canagliflozin 100-300 mg)
- How does SGLT2 inhibitors (canagliflozin / empagliflozin / dapagliflozin) work?
- Block sodium-glucose cotransporter 2 in the kidney's proximal tubule, spilling glucose into urine; beyond glucose-lowering they shift fuel use toward ketones, lower inflammation, and act as an indirect senolytic — enhancing immune clearance of senescent cells
This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.