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Head-to-head

Canagliflozin vs Metformin

The two most talked-about 'off-label longevity' diabetes drugs — one has a human aging trial in progress that still hasn't reported, the other has only mouse data.

By Julian RothResearch & dataUpdated October 2026

Short answer

Canagliflozin rests on firmer ground than metformin, with approval-level evidence against human clinical data. Canagliflozin is marketed for type 2 diabetes, while metformin is marketed for longevity, healthspan and metabolic aging, with thinner evidence behind that use. For canagliflozin, major cardiovascular events cut, hazard ratio 0.86 vs placebo, in the CANVAS Program of about 10,000 people with type 2 diabetes.

Canagliflozin

Invokana

FDA-approved

FDA-approved SGLT2 inhibitor with real cardiovascular and renal outcome trials (CANVAS, CREDENCE) — but the longevity claim rests entirely on a 14% median-lifespan extension in male-only NIA ITP mice; no human longevity trial exists, and the drug carries real risks (amputation, Fournier's gangrene, euglycemic DKA) that apply the same whether it's prescribed for diabetes or taken off-label for aging.

Full Canagliflozin evidence review

Metformin

Clinical data

An approved diabetes drug with an intriguing longevity hypothesis — but the dedicated aging trial (TAME) is still pending; longevity in healthy people is unproven.

Full Metformin evidence review

Canagliflozin vs Metformin: head to head

FDA status / approved use

Canagliflozin

FDA-approved (Invokana) for type 2 diabetes; longevity use is off-label and untested in humans

Metformin

Decades-old diabetes drug; taking it for longevity is off-label and unproven
Marketed for

Canagliflozin

Type 2 diabetes (approved); explored off-label for longevity on mouse ITP data

Metformin

Longevity, healthspan, metabolic aging
Outcome areas

Canagliflozin

Blood sugar / insulin sensitivity; Cardiovascular; Longevity / lifespan

Metformin

Longevity / lifespan; Blood sugar / insulin sensitivity
Evidence grade

Canagliflozin

FDA-approved

Metformin

Clinical data
How it works

Canagliflozin

Blocks the kidney's SGLT2 transporter so glucose leaves the body in urine

Metformin

Activates AMPK and reduces mTOR signaling, nutrient-sensing pathways tied to aging
Route and dosing

Canagliflozin

Oral tablet, prescription only

Metformin

Not established
Headline human result

Canagliflozin

Major cardiovascular events cut, hazard ratio 0.86 vs placebo, in the CANVAS Program of about 10,000 people with type 2 diabetes

Metformin

Observational only: diabetics on metformin survived as long as matched non-diabetics; the TAME outcome trial has not reported
Strongest evidence

Canagliflozin

Miller 2020 NIA ITP, JCI InsightCanagliflozin evidence reviewPubMed 32990681

Metformin

MILES/TAME rationale 2014Metformin evidence reviewPubMed 25041462
Key safety signal

Canagliflozin

Ketoacidosis, genital infections, Fournier's gangrene, volume depletion and raised lower-limb amputation risk

Metformin

Not established
How it is obtained

Canagliflozin

Prescription drug

Metformin

Prescription drug

marks a row where the two differ. “Not established” marks a cell the available evidence does not answer. Evidence grades come from our evidence matrix, which grades each molecule on the human data for the use it is marketed for.

FDA-approved:
Approved by the FDA for a defined indication, on the strength of pivotal human trials.
Clinical data:
Tested in humans — but investigational, discontinued, or proven only on a surrogate marker (not the marketed outcome).

Our verdict

Metformin's longevity case rests on an observational survival signal and mechanistic plausibility, with the dedicated human aging trial (TAME) still not reporting results after years — so its longevity claim is not more human-proven than canagliflozin's, just older and more discussed. Canagliflozin's case is entirely mouse-only ITP data, more recent, and specifically male-skewed. Both are approved for diabetes with real outcome trials in that indication; neither has ever been shown, in a human trial, to extend healthy lifespan.

Canagliflozin fits if

You're drawn to the more recent, replicated ITP signal and are comfortable with SGLT2-class risks (amputation, genital infection, euglycemic DKA).

Metformin fits if

You want the more-discussed, longer-track-record option, understanding that 'more discussed' isn't the same as 'more proven' — TAME hasn't reported.

Canagliflozin vs Metformin: common questions

Which has stronger human evidence, canagliflozin or metformin?
Canagliflozin. It has approval-level evidence (key source: Miller 2020 NIA ITP, JCI Insight), while metformin has human clinical data (key source: MILES/TAME rationale 2014).
What results have canagliflozin and metformin shown in people?
For canagliflozin, major cardiovascular events cut, hazard ratio 0.86 vs placebo, in the CANVAS Program of about 10,000 people with type 2 diabetes. The headline human result for metformin is observational only: diabetics on metformin survived as long as matched non-diabetics; the TAME outcome trial has not reported.

Key studies behind each

Canagliflozin

  1. Miller RA, Harrison DE, Allison DB, et al. (2020). Canagliflozin extends life span in genetically heterogeneous male but not female mice. JCI Insight. PubMed 32990681
  2. Jayarathne HSM, Debarba LK, Jaboro JJ, Ginsburg BC, Miller RA, Sadagurski M. (2022). Neuroprotective effects of Canagliflozin: Lessons from aged genetically diverse UM-HET3 mice. Aging Cell. PubMed 35707855
  3. Neal B, Perkovic V, Mahaffey KW, et al. (2017). Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes (CANVAS Program). N Engl J Med. PubMed 28605608
  4. Perkovic V, Jardine MJ, Neal B, et al. (2019). Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy (CREDENCE). N Engl J Med. PubMed 30990260

Metformin

  1. Bannister CA, Holden SE, Jenkins-Jones S, et al. (2014). Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes Metab. PubMed 25041462
  2. Kulkarni AS, Gubbi S, Barzilai N. (2020). Benefits of Metformin in Attenuating the Hallmarks of Aging. Cell Metab. PubMed 32333835
  3. Kulkarni AS, Brutsaert EF, Anghel V, et al. (2018). Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults (MILES). Aging Cell. PubMed 29383869
  4. Barzilai N, Crandall JP, Kritchevsky SB, et al. (2016). Metformin as a Tool to Target Aging. Cell Metab. PubMed 27304507

The full evidence reviews

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