← SGLT2 inhibitors × cardiovascular events

TrialJournal of the American Geriatrics Society2025

The Efficacy and Safety of Canagliflozin by Frailty Status in Participants of the CANVAS and CREDENCE Trials.

Tu N Nguyen et al.PubMed ↗Full text ↗Publisher ↗

  • Canagliflozincuts both waysLower major heart events, fewer Cardiovascular deaths, fewer deaths.Weak evidence: one subgroup.

What the trial testedrandomised · 14,543 people · 2025

One subgroup

May have lowered major heart events in frail

−20%−30% to −10%

canagliflozin vs placebo, in frail

Bigger than 4 in 10 for cardiovascular events

As reported

HR 0.80, 95% CI 0.70–0.90 · the paper's word: Major adverse cardiovascular events (MACE)

One subgroup

May have reduced Cardiovascular deaths in frail

−21%−33% to −5%

canagliflozin vs placebo, in frail

Bigger than 5 in 10 for cardiovascular events

As reported

HR 0.79, 95% CI 0.67–0.95 · the paper's word: Cardiovascular mortality

One subgroup

May have reduced deaths in frail

−19%−30% to −6%

canagliflozin vs placebo, in frail

Bigger than 6 in 10 for all-cause mortality

As reported

HR 0.81, 95% CI 0.70–0.94 · the paper's word: all-cause mortality

One subgroup

May have raised osmotic diuresis in frail

1.7×1.2× to 2.3×

canagliflozin vs placebo, in frail

Bigger than 7 in 10 for adverse events & safety

As reported

HR 1.67, 95% CI 1.22–2.28

+4 more in the walkthrough ↓

Who was studied, and how

14,543people with cardiovascular disease, in this paper

Among frail, the trial randomly assignedassigned by chance

canagliflozin
placebo

May have lowered major heart events−20%

May have reduced Cardiovascular deaths−21%

May have reduced deaths−19%

randomised · one subgroup

Among non-frail, the trial randomly assignedassigned by chance

canagliflozin
placebo

May have raised osmotic diuresis3×

No clear effect on major heart events−9%

No clear effect on Cardiovascular deaths−6%

randomised · one subgroup

the abstract, start to end

… and non-frail subgroups: HRs for MACE 0.80 (95% CI 0.70-0.90) in the frail versus 0.91 (95% CI 0.75-1.09) in the non-frail (p for interaction = 0.27); HRs for cardiovascular mortality 0.79 (95% CI 0.67-0.95) in the frail versus 0.94 (95% CI 0.70-1.27) in the non-frail (p for interaction = 0.38); HRs for all-cause mortality 0.81 (95% CI 0.70-0.94) in the frail versus 0.93 (95% CI 0.74-1.16) in the …

… except for osmotic diuresis (HRs 1.67, 95% CI 1.22-2.28 in the frail vs. 3.05, 95% CI 2.13-4.35 in the …

← favours treatmentfavours comparator →
could be chance
Major adverse cardiovascular events (MACE)canagliflozin vs placebo, in frail
HR 0.800.70–0.90
Major adverse cardiovascular events (MACE)canagliflozin vs placebo, in non-frail
HR 0.910.75–1.09
Cardiovascular mortalitycanagliflozin vs placebo, in frail
HR 0.790.67–0.95
Cardiovascular mortalitycanagliflozin vs placebo, in non-frail
HR 0.940.70–1.27
All-cause mortalitycanagliflozin vs placebo, in frail
HR 0.810.70–0.94
All-cause mortalitycanagliflozin vs placebo, in non-frail
HR 0.930.74–1.16
Osmotic diuresiscanagliflozin vs placebo, in frail
HR 1.671.22–2.28
Osmotic diuresiscanagliflozin vs placebo, in non-frail
HR 3.052.13–4.35
SGLT2 inhibitorsCardiovascular eventsAll-cause mortalityAdverse events & safety

SGLT2 inhibitors × cardiovascular eventshelps?mixed

unlikelylikely
0.500.50 without it

SGLT2 inhibitors × adverse events & safetyharms?mixed

unlikelylikely
0.000.00 without it

SGLT2 inhibitors × all-cause mortalityhelps?mixed

unlikelylikely
0.500.50 without it
← favours treatmentfavours comparator →
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4 papers cite it

2025
2026
this papercites it

3 trials

NCT01032629phase 34,330 enrolled2009NCT01989754phase 45,813 enrolled2014NCT02065791phase 34,401 enrolled2014
Full record →Abstract, authors, funding and every citing paper · PMID 40105285