April 1, 2026Open Access

Impact of SGLT2 Inhibitors on Mortality Across Different Populations: A Systematic Review and Meta-Analysis

Q: What does this research mean for the field?

SGLT2 inhibitors significantly reduce long-term all-cause and cardiovascular mortality in patients with heart failure, chronic kidney disease, and diabetes. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

SGLT2 inhibitors significantly reduced long-term all-cause mortality (RR 0.89) and cardiovascular mortality (RR 0.88) in patients with heart failure, chronic kidney disease, and diabetes.

Key Points

This review aims to evaluate the effect of SGLT2 inhibitors on mortality across different populations, focusing on both short and long-term outcomes.
Conducted a systematic search in four databases: PubMed, Scopus, WOS, and Cochrane CENTRAL.
Included randomized controlled trials comparing SGLT2 inhibitors to control regarding mortality outcomes.
Extracted outcomes included all-cause mortality, cardiovascular mortality, renal mortality, and in-hospital mortality.
Utilized RevMan and OpenMeta analyst software for meta-analysis and meta-regression.
SGLT2 inhibitors significantly reduced all-cause mortality with a relative risk (RR) of 0.89 for up to one year follow-up.
The most significant benefit was observed in patients treated during acute cardiac decompensation (RR = 0.76).
Beyond one year, there was a continued reduction in all-cause mortality (RR = 0.89), especially in individuals with chronic heart failure, CKD, and diabetes.
Cardiovascular mortality decreased overall with an RR of 0.88, primarily benefiting chronic heart failure and CKD subgroups.

Structured PICO

Do SGLT2 inhibitors reduce mortality across different patient populations?

Population

Patients across different populations, including those with acute cardiac decompensation, chronic heart failure, chronic kidney disease (CKD), and diabetes mellitus (DM) with established cardiovascular disease

Intervention

SGLT2 inhibitors

Comparator

Control

Outcome

All-cause mortality (up to one year and more than one year)hard clinical

SGLT2 inhibitors provide a consistent and significant reduction in all-cause and cardiovascular mortality across both short-term and long-term follow-up, with early benefits particularly evident during acute cardiac decompensation.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Sodium-glucose cotransporter-2 (SGLT2) inhibitors offer glucose-lowering, cardio-protective and reno-protective properties. Mortality rates constitute a central endpoint for understanding the overall clinical value of SGLT2 inhibitors. This systematic review and meta-analysis aims to compare mortality outcomes associated with SGLT2 inhibitors across different populations. A systematic search was performed in four databases—PubMed, Scopus, Web of Science (WOS) and Cochrane CENTRAL—in March 2025. We strictly included randomized controlled trials (RCTs) that compared patients who received SGLT2is to control patients regarding mortality outcomes. All-cause mortality up to one year, all-cause mortality more than one year, cardiovascular mortality, renal mortality and in-hospital mortality were the extracted outcomes. Finally, RevMan (5.4) was adopted for meta-analysis, and OpenMeta analyst software was adopted for meta-regression. Fifty clinical trials met the eligibility criteria of the current systematic review and meta-analysis. SGLT2 inhibitors significantly reduced all-cause mortality in studies with follow-up of up to one year (RR = 0.89, 95% CI 0.80–0.99, p = 0.03). This early survival benefit was primarily driven by the subgroup of patients treated during acute cardiac decompensation (RR = 0.76, 95% CI 0.60–0.97, p = 0.03). Furthermore, long-term follow-up beyond one year showed a significant reduction in all-cause mortality (RR = 0.89, 95% CI 0.85–0.94, p < 0.0001), particularly among patients with chronic heart failure, chronic kidney disease (CKD), and diabetes mellitus (DM) with established cardiovascular disease (CVD) (following sensitivity analyses). Cardiovascular mortality was also significantly reduced overall (RR = 0.88, 95% CI 0.84–0.94, p < 0.0001), with the greatest benefit observed in chronic heart failure and CKD subgroups. SGLT2 inhibitors as a class provide a consistent and significant reduction in all-cause mortality across both short-term (up to one year) and long-term follow-up. The early survival benefit is particularly evident when initiated during acute cardiac decompensation, while the long-term benefit extends to chronic heart failure, CKD, and high-risk DM. Future well-designed trials are needed to address the impact of less-explored SGLT2 inhibitors and understudied populations.