Effects of sodium-glucose cotransporter 2 inhibitors on cardiomyopathy: a meta-analysis.

Background: Cardiomyopathies can present at any age and affect individuals and families across the entire life course. Clinical effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cardiomyopathy have not yet been fully elucidated.

Objective: The primary objective of this study was to investigate whether SGLT2 inhibitors have an effect on cardiomyopathy compared to placebo.

Methods: We systematically searched for randomized double-blind placebo-controlled trials on PubMed, Web of Science, EU Clinical Trials Register, and ClinicalTrials.gov. We used the Mantel-Haenszel statistical method, fixed-effects model and risk ratio (RR) with 95% confidence intervals (CI) to analyze binary data.

Results: A total of 19 studies were included, covering 97,035 participants. Compared to placebo, SGLT2 inhibitors were associated with a reduced risk of cardiomyopathy (RR 0.72; 95% CI 0.56-0.92; P < 0.01; high certainty of evidence), with non-significant heterogeneity (P_{heterogeneity}=0.81; I² = 0%), especially observed in the empagliflozin subgroup (RR 0.66; 95% CI 0.46-0.94; P = 0.02), chronic kidney disease (RR 0.67; 95% CI 0.47-0.97; P = 0.03) population and heart failure (RR 0.46; 95% CI 0.23-0.91; P = 0.03) population. However, in type 2 diabetes mellitus population, the effect of SGLT2 inhibitors on cardiomyopathy incidence was less clear (RR 0.76; 95% CI 0.51-1.12; P = 0.17; moderate certainty of evidence). Additionally, SGLT2 inhibitors were associated with a reduced risk of primary cardiomyopathy (RR 0.43; 95% CI 0.21-0.87; P = 0.02) and slightly decreased the incidence of secondary cardiomyopathy compared to placebo (RR 0.75; 95% CI 0.56-1.01; P = 0.06).

Conclusions: SGLT2 inhibitors significantly reduced the risk of cardiomyopathy, which further enhances the cardiovascular benefits of SGLT2 inhibitors in clinical settings, especially for patients with heart failure and chronic kidney disease.