SGLT2 inhibitors reduce cardiorenal deaths

SGLT2 inhibitors reduced cardiovascular and kidney-related deaths, but not overall deaths, in pooled trial data.
*Systematic review and meta-analysis of RCTs; Level 1a.

Citation

Jaiswal V, Mashkoor Y, Waqas M, et al. All-cause and cause-specific mortality assessment in patients receiving sodium glucose co-transporter-2 inhibitors. The American Journal of Medicine. 2026;139:1032-1042.

Background

SGLT2 inhibitors are widely used for diabetes, heart failure, and chronic kidney disease because they reduce heart failure and kidney events. Their effect on different causes of death has been less consistent across trials.

Patients

Adults 18 years or older with diabetes, heart failure, or chronic kidney disease from 18 randomized trials. Excluded studies included animal studies, reviews, case reports, single-arm studies, pediatric studies, and studies without relevant mortality outcomes.

Intervention

SGLT2 inhibitors: canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, or sotagliflozin.

Control

Placebo or usual control therapy, generally added to standard background care.

Outcome

Primary outcome: all-cause mortality. Secondary outcomes: cardiovascular, non-cardiovascular, and kidney-related mortality.

Follow-up Period

Mean follow-up was 2.2 years.

Results

The analysis included 95,913 patients.

Outcome Result
Cardiovascular mortality Reduced; risk ratio 0.86 (95% confidence interval, 0.81-0.92)
Kidney-related mortality Reduced; risk ratio 0.31 (95% confidence interval, 0.11-0.90)
All-cause mortality in adults older than 65 years Reduced; risk ratio 0.93 (95% confidence interval, 0.87-0.98)
Non-cardiovascular mortality in adults younger than 65 years Reduced; risk ratio 0.87 (95% confidence interval, 0.78-0.96)

Overall all-cause mortality and overall non-cardiovascular mortality were not significantly reduced. The age-based findings were exploratory.

Limitations

Many included trials were not designed primarily to measure death, so event numbers were limited. The all-cause mortality analysis had substantial variation across studies. Kidney-related mortality came from only three trials. Subgroup findings used trial-level data and should not be treated as definitive patient-level evidence.

Funding

No funding disclosed; several authors reported industry relationships.

Clinical Application

Use SGLT2 inhibitors when indicated for heart failure, chronic kidney disease, or diabetes; mortality benefit is strongest for cardiovascular and kidney-related death.