Abstract

Background Statins are first-line therapeutic agents for metabolic syndrome, but their muscular adverse effects increase the metabolic burden in Type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). QiShenYiQi dropping pills (QSYQ), a compound Chinese medicine, exerts cardioprotective and metabolic regulatory effects. However, whether it is beneficial to gut microbiota dysbiosis and statin-associated muscle symptoms (SAMS) remains unclear. Methods The disease model with T2DM complicated with CHD was established in APOE −/− mice. The mice were randomly divided into normal control (NC), disease model (DM), Simvastatin + Fenofibrate (SF), Simvastatin + Fenofibrate + QSYQ (SFQ), and Simvastatin + Fenofibrate + Trimetazidine (SFT) groups, with 90 days of intervention. Using 16S rRNA sequencing, untargeted metabolomics, and transcriptomics, we investigated the regulatory effects and mechanism of QSYQ on unbalanced microbiota composition and SAMS. Results Combination therapy with QSYQ markedly ameliorated glycemic and lipid profiles in animals with comorbid T2DM and CHD, and outperformed other treatment strategies in preserving hepatic and skeletal muscle function. These beneficial effects may be correlated to the regulation of gut microbiota, glycolipid metabolites and associated gene expression, including inflammation-related genes, apoptosis-related genes, as well as antioxidant and energy metabolism-related genes. Conclusion These findings suggested the potential value of QSYQ as a promising candidate for T2DM and CHD, attenuating the side effects of statins, providing a novel complementary strategy for clinical treatment.