TL;DR: Metformin has been the poster drug for anti-aging research for over a decade, but it has not yet proven it can slow aging in healthy humans. SGLT2 inhibitors — particularly canagliflozin — have produced one of the most striking lifespan extensions in male mice from the NIA Interventions Testing Program, while also showing strong heart and kidney benefits in people with diabetes. As of 2026, neither drug is approved for longevity, and neither should be taken by healthy people for that purpose.
🐢 Tortoise Wisdom
"Metformin is a safe old drug with weak anti-aging proof. SGLT2 inhibitors have stronger organ-protection proof but no healthy-aging trial. Both are diabetes medicines, not longevity pills."
1. Metformin: The Original Longevity Candidate
Metformin is a biguanide used for type 2 diabetes since the 1950s. Its possible anti-aging mechanisms include:
- AMPK activation, which mimics some effects of calorie restriction.
- Reduced hepatic glucose production and improved insulin sensitivity.
- Modest reductions in inflammation, IGF-1 signalling and mTOR activity.
- Possible effects on the gut microbiome.
Human evidence
- TAME (Targeting Aging with Metformin) trial: designed to test whether metformin delays the onset of multiple age-related diseases in older adults. It is a landmark trial, but as of 2026 it has not reported primary results.
- Observational studies: some epidemiology suggests diabetics on metformin may live longer than those on other treatments, but these comparisons are confounded by disease severity and other drugs.
- UK Prospective Diabetes Study (UKPDS): metformin reduced cardiovascular events and mortality in overweight type 2 diabetics, but this is diabetes-specific evidence, not anti-aging evidence.
Read our deeper dive on metformin, the TAME trial and its risks.
2. SGLT2 Inhibitors: The New Contenders
Sodium-glucose cotransporter-2 (SGLT2) inhibitors block glucose reabsorption in the kidney proximal tubule, causing glucose to be excreted in urine. Examples include:
- Canagliflozin
- Dapagliflozin
- Empagliflozin
- Ertugliflozin
Beyond glucose lowering, they reduce blood pressure, body weight, uric acid and inflammation. Their real-world impact on heart failure and kidney disease has been transformative.
Mouse lifespan evidence
- Canagliflozin in the ITP: a 2020 JCI Insight study reported that canagliflozin extended lifespan in genetically heterogeneous male mice by approximately 14%. It also reduced body weight, fasting glucose and tumour burden. There was no significant lifespan extension in female mice (Harrison et al., 2020).
- Mechanistic overlap: a 2023 Life Sciences paper found that canagliflozin shares mTOR and MAPK signalling mechanisms with other lifespan-extending treatments (Jiang et al., 2023).
Senolytic-like effects
A 2024 Nature Aging study reported that SGLT2 inhibition can eliminate senescent cells and alleviate pathological aging in mouse models, suggesting senolytic or senomorphic activity may be part of the mechanism (Nature Aging 2024).
4. Could SGLT2 Inhibitors Be Better Geroprotectors?
Several features make SGLT2 inhibitors interesting beyond diabetes:
- Cardiorenal protection: large trials (DAPA-HF, EMPEROR, CREDENCE) show reduced heart failure hospitalisation and kidney disease progression even in non-diabetic patients.
- Anti-inflammatory effects: SGLT2 inhibitors lower inflammatory markers such as CRP and uric acid.
- Ketone elevation: they increase circulating ketones, which some researchers believe could provide alternative fuel for the heart and brain.
- Senescent-cell clearance: preclinical work suggests they may reduce senescent-cell burden in tissues.
However, these benefits have been demonstrated in people who already have cardiovascular or kidney disease. Whether they prevent aging in healthy people is unknown.
5. Risks and Realistic Use
Both drug classes are prescription medicines with real risks. In the UK:
- Metformin is first-line for type 2 diabetes and sometimes used for prediabetes/PCOS. It requires kidney-function monitoring.
- SGLT2 inhibitors are used for type 2 diabetes, heart failure with reduced ejection fraction and chronic kidney disease. They require monitoring for infections, dehydration and rare ketoacidosis.
⚠️ Important: Healthy people should not take prescription diabetes drugs for unproven longevity benefits. Doing so risks side effects, drug interactions and masking of real health problems. Join a clinical trial if you want to contribute to the science.
7. FAQ
What are SGLT2 inhibitors?
SGLT2 inhibitors are a class of type 2 diabetes drugs that block glucose reabsorption in the kidneys, lowering blood sugar. Examples include canagliflozin, dapagliflozin and empagliflozin.
Did SGLT2 inhibitors extend lifespan in mice?
Yes, in one ITP study canagliflozin extended lifespan in genetically heterogeneous male mice by approximately 14%. It did not significantly extend lifespan in female mice.
Is metformin proven to extend lifespan?
No. Metformin extends lifespan in some worm and mouse models, but human trials such as TAME are designed to measure delayed onset of age-related diseases, not lifespan. No definitive human longevity result has been published.
Are SGLT2 inhibitors safer than metformin?
Both have risks. SGLT2 inhibitors can cause genital infections, urinary tract infections, dehydration and rare ketoacidosis. Metformin commonly causes GI upset and is contraindicated in severe kidney disease. Neither is risk-free.
Should healthy people take these drugs for longevity?
No. These are prescription drugs for diabetes, heart failure or chronic kidney disease. Healthy people should not take them for unproven anti-aging benefits without enrolling in a clinical trial.