SGLT2 inhibitor cardiorenal benefit is established, but clinicians still hesitate in older patients, partly because trial populations skew younger and partly because hypotension and volume depletion feel more threatening with age. This individual participant data meta-analysis addressed the age question directly.
Investigators obtained subject-level datasets from CANVAS and CREDENCE through the Yale Open Data Access project and restricted the analysis to participants aged 50 or over — 3,955 from CANVAS and 4,035 from CREDENCE. Cox models were stratified by age tertile and trial-level results pooled.
For end-stage kidney disease, with 175 events, the pooled hazard ratio was 0.535 (95% CI 0.392 to 0.729), a 46.5% relative reduction. The CREDENCE-specific hazard ratio was 0.518 (0.376 to 0.714, p<0.001); CANVAS contributed little precision at 0.853 (0.250 to 2.916). The number needed to treat at three years in CREDENCE was 27.5.
Cardiovascular mortality, with 309 events, showed a pooled hazard ratio of 0.841 (95% CI 0.669 to 1.058) — favourable but not significant, which the authors attribute to limited power.
A number needed to treat of 27.5 over three years to prevent one case of end-stage kidney disease is among the more favourable figures in nephrology, and it applies to a population that is undertreated. In Indian practice, where dialysis access is limited and largely paid for privately, preventing kidney failure has a value that a number needed to treat does not capture: it is the difference between a chronic clinic patient and a family selling assets.
- Do not withhold an SGLT2 inhibitor on the basis of age alone in adults over 50 with diabetic kidney disease
- Quote the number needed to treat: about 28 patients over three years to prevent one case of end-stage kidney disease
- Expect the cardiovascular mortality benefit to be real but unproven in this age-restricted analysis
- Counsel on volume status, sick-day rules and genital mycotic infection at initiation, as with any SGLT2 inhibitor
- Note that almost all the kidney benefit here comes from CREDENCE, which enrolled patients with albuminuric diabetic kidney disease
The statistics, in plain English
The two trials contributed very unequally, and it shows. CANVAS gave a hazard ratio of 0.853 with an interval from 0.250 to 2.916 — so wide it carries almost no information, because CANVAS enrolled patients with far fewer kidney events. CREDENCE gave 0.518 with an interval of 0.376 to 0.714. The pooled figure of 0.535 is therefore essentially CREDENCE's result. That is not a flaw, but it does mean the finding applies most confidently to CREDENCE-like patients with albuminuric diabetic kidney disease. The cardiovascular mortality interval, 0.669 to 1.058, crosses 1.0 and should not be reported as a benefit.
Read the rest in the app
You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.
Scan to keep reading on your phone. No account needed to start.
Tomorrow morning, before your first patient
One edition a day for nephrology, written by the desk, every claim tied to its paper. Six minutes.
Get the app — free