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Cgz4.5

Canagliflozin Research

Mostly mechanism / observationalLimited safety

7 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most Canagliflozin studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from medium-quality meta-analyses and randomised trials published 2015–2022 with a typical study size of 7,020 participants.

Based on 7 studies · 1 meta-analysis · 4 RCTs · 21,563 total participants

Confidence

Moderate

By outcome

Cardiovascular & heart failure
Mostly mechanism / observational5 studies
Glucose & weight
Mostly mechanism / observational4 studies
Lifespan & aging (preclinical)
Mostly mechanism / observational3 studies
Safety profile
Too few graded studies1 study

Steady research

2 studies in the last 5 years · Latest meta-analysis: 2020

20152022

1RCTn=7,020 · very large study2015

An SGLT2 inhibitor (empagliflozin) reduced cardiovascular death and all-cause mortality in type 2 diabetes.

Zinman, Wanner, Lachin, Fitchett, Bluhmki, Hantel · The New England journal of medicine (2015)

EMPA-REG OUTCOME randomized trial (empagliflozin, same class)
Reduced cardiovascular death, heart-failure hospitalization, and all-cause mortality
Landmark evidence for SGLT2-class cardiovascular benefit

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2RCT2021

An SGLT2 inhibitor reduced heart-failure events in patients with preserved ejection fraction.

Anker, Butler, Filippatos, Ferreira, Bocchi, Böhm · The New England journal of medicine (2021)

EMPEROR-Preserved randomized trial (empagliflozin)
Reduced heart-failure hospitalization even in HFpEF, including non-diabetics
Extends SGLT2 benefit beyond diabetes

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3RCTn=10,142 · very large study2017

In the CANVAS Program, canagliflozin reduced cardiovascular events but increased the risk of lower-limb amputation in type 2 diabetes.

Neal, Perkovic, Mahaffey, de Zeeuw, Fulcher, Erondu · The New England journal of medicine (2017)

CANVAS Program: canagliflozin vs placebo in 10,142 high-cardiovascular-risk type-2 diabetics
Reduced the composite of cardiovascular death, MI, and stroke, plus heart-failure and renal outcomes
Canagliflozin's OWN pivotal cardiovascular trial (distinct from the class evidence cited elsewhere)

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4RCTn=4,401 · very large study2019

In CREDENCE, canagliflozin reduced kidney failure and cardiovascular events in type 2 diabetes with nephropathy.

Perkovic, Jardine, Neal, Bompoint, Heerspink, Charytan · The New England journal of medicine (2019)

CREDENCE randomized trial in type-2 diabetics with albuminuric chronic kidney disease (n=4,401)
Reduced kidney failure, dialysis, and renal/cardiovascular death; stopped early for efficacy
The first dedicated renal-outcomes SGLT2 trial — establishes canagliflozin's renal protection directly

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5Meta-Analysis2020

SGLT2 inhibitors reduced events in patients with heart failure with reduced ejection fraction.

Zannad, Ferreira, Pocock, Anker, Butler, Filippatos · Lancet (London, England) (2020)

Meta-analysis of SGLT2 inhibitors in heart failure with reduced ejection fraction
Consistent reductions in cardiovascular death and heart-failure hospitalization
Quantitative confirmation of class cardiorenal benefit

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6Animal2020

Canagliflozin extended life span in genetically heterogeneous male but not female mice.

Miller, Harrison, Allison, Bogue, Debarba, Diaz · JCI insight (2020)

NIA Interventions Testing Program: canagliflozin extended lifespan in male mice
No lifespan benefit in females — a sex-specific effect
Linked to improved glucose handling and metabolic effects

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7Animal2022

Canagliflozin showed neuroprotective effects in aged genetically diverse mice.

Jayarathne, Debarba, Jaboro, Ginsburg, Miller, Sadagurski · Aging cell (2022)

Follow-up study of canagliflozin in aged UM-HET3 mice
Suggested neuroprotective/cognitive benefits with aging
Extends the geroprotector rationale beyond lifespan

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View in Research Library

Canagliflozin Research

Mostly mechanism / observational

Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes.

Empagliflozin in Heart Failure with a Preserved Ejection Fraction.

Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes.

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy.

SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials.

Canagliflozin extends life span in genetically heterogeneous male but not female mice.

Neuroprotective effects of Canagliflozin: Lessons from aged genetically diverse UM-HET3 mice.