Cardiovascular Outcomes of Sglt-2 Inhibitors’ Subtypes in Type 2 Diabetes; an Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials Publisher



Ebrahimi P^{1, 10} ; Soleimani H² ; Mahalleh M³ ; Farisi P³ ; Taheri M⁴ ; Ramezani P⁵ ; Soltani P⁶ ; Nazari R⁶ ; Senobari N⁶ ; Mousavinezhad SM⁷ ; Payab M^{1, 10} ; Gooshvar M⁷ ; Zadeh AZ⁷ ; Hosseini K³ Show All Authors Show Affiliations
Source: Journal of Diabetes and Metabolic Disorders Published:2025

Abstract

Introduction: The effects of Sodium-glucose cotransporter-2 (SGLT-2) inhibitors on cardiac outcomes, cardiovascular mortality (CVM), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients have been reported heterogeneously in different studies. Methods: PubMed, Scopus, Embase, Cochrane Library, and Scholar databases were searched with relevant MeSH terms from January 1, 2010, to November 14, 2023. The study used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The primary outcomes in all trials included the risk of ACM, CVM, hospitalization for heart failure (HHF), myocardial infarction (MI), and cerebrovascular accidents (CVA) in T2DM patients who were treated with one of the SGLT-2 inhibitors. Heterogeneity between studies was evaluated using Cochran’s Q and I2 tests. The Egger’s test was used to check for publication bias. Results: Eighteen studies, including 70,830 participants, were included. A pooled estimate showed that SGLT-2 inhibitor treatment was significantly associated with reduced ACM (OR: 0.82, 95% CI: 0.75–0.90, p-value: 0.001, I2: 35.1%), CVM (OR: 0.88, 95% CI: 0.80–0.96, p-value: 0.001, I2: 0%), MI (OR: 0.88, 95% CI: 0.79–0.98, p-value: 0.001, I2: 0%), and HHF (OR: 0.67, 95% CI: 0.58–0.77, p-value: 0.001). SGL-2 inhibitor treatment had no significant relationship with CVA (stroke) (OR: 0.95, 95% CI: 0.8–1.10, p-value: 0.896). Subgroup analysis showed that the effect of SGLT-2 inhibitor treatment on outcomes varied based on the type of SGLT-2 inhibitor. Conclusion: SGLT-2 inhibitor treatment significantly reduced CVM, ACM, MI, and HHF. Empagliflozin, Canagliflozin, and Dapagliflozin significantly reduced ACM. Canagliflozin was significantly associated with a reduction in CVM. All SGLT-2 inhibitor treatments were associated with a reduction in HHF. © The Author(s), under exclusive licence to Tehran University of Medical Sciences 2024.