Reliability of Metformin’s protective effects against doxorubicin-induced cardiotoxicity: a meta-analysis of animal studies
Abstract
Background The protective effects of metformin (Met) against doxorubicin (Dox)-induced cardiotoxicity via potential hypotheses of mechanisms of action with unknown reliability and credibility. Objectives This study aimed to investigate the protective effects of Met against Dox-induced cardiotoxicity and the underlying mechanisms of action, as well as examine their reliability and credibility. Methods A comprehensive search was conducted within the PubMed, Embase, Web of Science, Science Direct, Scopus, and CNKI databases from inception to 31 December 2023. Animal experiments evaluating the efficacy of Met against Dox-induced cardiotoxicity were included in this study. The primary efficacy outcomes were markers of myocardial injury. Effect size was measured using the standardized mean difference for continuous variables. Data were pooled using a random-effects model in the Stata 18 statistical software package. Results Twenty-one studies involving 203–208 animals treated with Dox and 271–276 animals treated with Dox and Met were included in this analysis. Quality assessment revealed high-quality scores. Pooled results favored Met treatment based on the serum lactate dehydrogenase (LDH), creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI), and aspartate aminotransferase levels. Sensitivity analysis using the leave-one-out method demonstrated stable results. Funnel plots, Egger’s test, and Begg’s test confirmed potential publication bias. The oxidative stress…
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