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