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Cardiovascular outcomes of SGLT-2 inhibitors' subtypes in type 2 diabetes; an updated systematic review and
Pouya Ebrahimi1,2, Hamidreza Soleimani3, Mehrdad Mahalleh4
1Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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.
Insights
Sodium-glucose cotransporter-2 (SGLT-2) inhibitors significantly reduce cardiovascular mortality, all-cause mortality, myocardial infarction, and heart failure hospitalizations in type 2 diabetes mellitus patients. These SGLT-2 inhibitors show promising results for improving cardiac outcomes.
Area of Science:
- Cardiology
- Endocrinology
- Pharmacology
Background:
- Type 2 diabetes mellitus (T2DM) patients face heterogeneous outcomes with Sodium-glucose cotransporter-2 (SGLT-2) inhibitors regarding cardiac events and mortality.
- Previous studies on SGLT-2 inhibitors in T2DM have yielded varied results, necessitating a comprehensive analysis.
Purpose of the Study:
- To systematically evaluate the efficacy of SGLT-2 inhibitors in reducing major adverse cardiac events and mortality in T2DM patients.
- To synthesize evidence from multiple studies to provide a pooled estimate of SGLT-2 inhibitor effects on cardiovascular outcomes.
Main Methods:
- A systematic review and meta-analysis adhering to PRISMA guidelines was conducted.
- Searches were performed across PubMed, Scopus, Embase, Cochrane Library, and Scholar databases (January 2010 - November 2023).
- Primary outcomes included all-cause mortality, cardiovascular mortality, hospitalization for heart failure, myocardial infarction, and cerebrovascular accidents.
Main Results:
- Eighteen studies with 70,830 participants were analyzed.
- SGLT-2 inhibitors significantly reduced all-cause mortality (OR: 0.82), cardiovascular mortality (OR: 0.88), myocardial infarction (OR: 0.88), and hospitalization for heart failure (OR: 0.67).
- No significant association was found with cerebrovascular accidents (stroke) (OR: 0.95); however, subgroup analyses indicated varied effects based on specific SGLT-2 inhibitor agents.
Conclusions:
- SGLT-2 inhibitor treatment demonstrably lowers cardiovascular mortality, all-cause mortality, myocardial infarction, and hospitalization for heart failure in T2DM patients.
- Specific agents like Empagliflozin, Canagliflozin, and Dapagliflozin were associated with reduced all-cause mortality, while Canagliflozin also showed a significant reduction in cardiovascular mortality.
- All evaluated SGLT-2 inhibitors were effective in reducing hospitalization for heart failure.
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