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All-cause and cause-specific mortality assessment in patients receiving sodium glucose co-transporter-2 inhibitors

Vikash Jaiswal1, Yusra Mashkoor2, Muhammad Waqas3

  • 1Endeavor Center for Cardiovascular Intervention Outcomes Research and Evaluation (ECCORE), Section of Interventional Cardiology, Endeavor Health Cardiovascular Institute, University of Chicago Pritzker School of Medicine, Ill, USA.

The American Journal of Medicine
|March 28, 2026
PubMed
Abstract

Insights

Sodium glucose co-transporter-2 inhibitors (SGLT2i) reduce cardiovascular and renal mortality in patients with diabetes, heart failure, and kidney disease. Exploratory analysis suggests SGLT2i may benefit all-cause mortality in older adults and non-cardiovascular mortality in younger patients.

Area of Science:

  • Cardiology
  • Nephrology
  • Endocrinology

Background:

  • Sodium glucose co-transporter-2 inhibitors (SGLT2i) are established for cardiovascular and renal benefits.
  • Previous trials show inconsistent effects of SGLT2i on all-cause and cause-specific mortality.
  • This study evaluates SGLT2i's impact on mortality in patients with diabetes mellitus, heart failure, or chronic kidney disease.

Purpose of the Study:

  • To systematically evaluate the association between SGLT2 inhibitors and all-cause mortality.
  • To assess the impact of SGLT2 inhibitors on cause-specific mortality.
  • To explore potential benefits across different age groups and conditions.

Main Methods:

  • Systematic literature search of randomized controlled trials (RCTs) up to September 10, 2025.
  • Meta-analysis using a random-effects model to calculate risk ratios (RRs) and 95% confidence intervals (CIs).
  • Analysis included 18 RCTs with a total of 95,913 patients.

Main Results:

  • SGLT2 inhibitors did not significantly reduce overall all-cause mortality (RR: 0.92 [95% CI, 0.80-1.05]).
  • A significant reduction in cardiovascular mortality (RR: 0.86 [95% CI, 0.81-0.92]) and renal mortality (RR: 0.31 [95% CI, 0.11-0.90]) was observed.
  • Subgroup analyses indicated a potential all-cause mortality benefit in older adults (>65 years) and non-cardiovascular mortality benefit in younger patients (<65 years).

Conclusions:

  • SGLT2 inhibitors are pivotal in cardiorenal therapy, significantly reducing cardiovascular and renal mortality.
  • Findings suggest potential personalized benefits of SGLT2i for all-cause mortality in older adults.
  • Exploratory results indicate possible non-cardiovascular mortality benefits in younger individuals, supporting lifespan therapy considerations.
Keywords:
Cardiovascular mortalityChronic kidney diseaseDiabetesHeart failureMortalityOutcome analysisSGLT2i

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