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Canagliflozin (Invokana) — SGLT2 inhibitor
An SGLT2-inhibitor diabetes drug (Invokana) that lowers glucose by excreting it in urine. It extended lifespan in male mice in the NIA aging program, and the SGLT2 class has strong proven cardiovascular, kidney, and heart-failure benefits in humans. Longevity benefit itself is unproven; carries genital-infection and (rarely) ketoacidosis risks. Prescription drug, not a supplement.
Prescription medication — not a dietary supplement
Canagliflozin is a prescription (or investigational) drug, not a supplement. It is included here for reference because people research and discuss it (often used off-label) — not as a recommendation. Take it only under a qualified clinician's supervision and only as prescribed; do not source it from grey-market vendors, where identity, purity, and dosing are unverified. The evidence below reflects its clinical trials.
What the evidence says
Most Canagliflozin studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.
Most evidence is from high-quality meta-analyses and randomised trials published 2014–2026 with a typical study size of 2,573 participants.
Based on 162 studies · 22 meta-analyses · 131 RCTs · 860,331 total participants
Confidence
High confidenceBy outcome
Canagliflozin extended lifespan in male mice (NIA ITP) and the SGLT2 class has strong proven cardiovascular, heart-failure, and kidney benefits in humans — but those are not a demonstrated longevity outcome, the mouse effect is male-specific, and the class carries genital-infection and ketoacidosis risks, so the longevity use stays emerging.
148 rigorous studies
129 randomized trials · 15 meta-analyses · 12 systematic reviews
Our evidence rating for Canagliflozin is accountable to this entire body of rigorous research indexed in PubMed — not a hand-picked subset.
PubMed · as of Jul 2026
24 trials ongoing or recruiting · 126 completed on ClinicalTrials.gov
43 of the completed trials have posted results
Registered trials show research momentum for Canagliflozin, not proof of effect — a registration is a plan, and posted results are sponsor-reported, not peer-reviewed. They are never counted toward the evidence rating above.
Browse these trials on ClinicalTrials.govClinicalTrials.gov · as of Aug 2026
Canagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor — a 'gliflozin' — that lowers blood glucose by blocking renal glucose reabsorption, causing glucose (and calories) to be excreted in the urine.
Beyond glucose-lowering it induces mild caloric loss, modest weight and blood-pressure reduction, and a metabolic shift toward fat/ketone utilization.
In the NIA Interventions Testing Program, canagliflozin extended lifespan in genetically heterogeneous male (but not female) mice, and follow-up work suggested neuroprotective effects in aged mice — putting it on the geroprotector map.
Crucially, the broader SGLT2 class has among the strongest human outcome evidence of any 'metabolic' drug class: large randomized trials (with empagliflozin, dapagliflozin, and canagliflozin) show reduced cardiovascular death, heart-failure hospitalization, and progression of kidney disease — benefits that extend even to non-diabetics with heart failure or chronic kidney disease.
The honest distinction: those proven benefits are cardiovascular/renal, not a demonstrated lifespan/longevity extension, and the mouse lifespan result is male-specific.
Class risks include genital mycotic infections, volume depletion, a rare but serious euglycemic diabetic ketoacidosis, and (specific to canagliflozin in one trial) a debated amputation/fracture signal.
Canagliflozin is a prescription drug; using an SGLT2 inhibitor off-label for longevity is increasingly discussed but the longevity benefit is unproven. The score reflects genuinely strong human cardiovascular/renal outcome data plus a male-mouse lifespan signal, against unproven human longevity and real class risks.
Blocks renal SGLT2, so glucose (and ~200–300 kcal/day) is excreted in urine, lowering blood glucose independent of insulin.
Urinary calorie loss plus a shift toward fat/ketone utilization drives modest weight loss and metabolic effects proposed to underlie the longevity signal.
Hemodynamic and metabolic effects (reduced preload, improved cardiac energetics, lower intraglomerular pressure) underlie the proven heart-failure and kidney benefits.
How Canagliflozin works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Caution — combined with carb restriction, SGLT2 inhibition can raise ketoacidosis risk.
Monitor for volume depletion and falls.
May be a poor fit — glucosuria promotes recurrence.
Additive volume depletion / hypotension.
Increased hypoglycemia risk (and ketoacidosis if insulin is reduced too much).
Tip: Glucosuria promotes yeast; hygiene and prompt treatment help.
Tip: Stay hydrated; caution with diuretics or in the elderly.
Tip: Can occur at near-normal glucose; seek care for nausea/malaise/rapid breathing, especially when fasting or ill.
Canagliflozin has an evidence score of 4.5/10 — emerging evidence based on 136 indexed studies, including 1 meta-analysis. An SGLT2-inhibitor diabetes drug (Invokana) that lowers glucose by excreting it in urine. It extended lifespan in male mice in the NIA aging program, and the SGLT2 class has strong proven cardiovascular, kidney, and heart-failure benefits in humans. Longevity benefit itself is unproven; carries genital-infection and (rarely) ketoacidosis risks. Prescription drug, not a supplement. Representative study: PMID 32877652.
The commonly studied dose of Canagliflozin is Off-label use mirrors diabetes dosing (e.g. 100–300 mg once daily before the first meal) under a clinician. A prescription drug; not an approved longevity regimen.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
The best time to take Canagliflozin is in the morning. It can be taken on an empty stomach. Taken before the first meal of the day; ensure adequate hydration and genital hygiene to limit infection risk.
Canagliflozin should be used with caution — talk to a healthcare provider before taking it. The most commonly reported side effects are genital yeast infection, volume depletion / dizziness, euglycemic diabetic ketoacidosis. Use caution if any of these apply to you: Type 1 diabetes (ketoacidosis risk); Severe renal impairment / dialysis; History of recurrent diabetic ketoacidosis.
Berberine
Likely helpsActivates AMPK to regulate blood sugar, improve insulin sensitivity, and support lipid metabolism — comparable to metformin in some trials.
Orlistat
Mostly mechanism / observationalA gastrointestinal lipase inhibitor that blocks roughly 30% of dietary fat from being absorbed. It is the only weight-loss drug sold both on prescription (Xenical 120 mg) and over the counter (Alli 60 mg). The evidence base is large and old: across 16 long-term randomised trials it produces about 2.9 kg more weight loss than placebo, and in the 4-year XENDOS trial it cut new type 2 diabetes from 9.0% to 6.2%, though exploratory analysis found the effect was detectable ONLY in the ~21% of participants who already had impaired glucose tolerance. The trade-off is that the unabsorbed fat leaves in the stool — oily spotting, faecal urgency and steatorrhoea — and it measurably impairs fat-soluble vitamin absorption, which is what drives its real drug interactions (warfarin, levothyroxine, ciclosporin). Modest, unglamorous, and hard to stay on.
Empagliflozin
Mostly mechanism / observationalAn SGLT2-inhibitor diabetes drug (Jardiance) with the strongest human outcome evidence of its class — it cuts cardiovascular death, heart-failure hospitalization, and kidney-disease progression even in non-diabetics. The most widely used SGLT2 for off-label 'longevity,' though longevity itself is unproven (the lifespan data are for sibling canagliflozin in mice). A prescription drug, not a supplement.
Dapagliflozin
Mostly mechanism / observationalAn SGLT2-inhibitor diabetes drug (Farxiga/Forxiga) with broad, robust human outcome evidence — it cuts heart-failure hospitalization and cardiovascular death across the ejection-fraction spectrum and slows kidney-disease progression, including in non-diabetics. The sibling of empagliflozin, used off-label for 'longevity,' though longevity itself is unproven (the lifespan data are for sibling canagliflozin in mice). A prescription drug, not a supplement.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 162 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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