Comparison of efficacy and safety of pioglitazone and SGLT2 inhibitors in treating Asian patients in MASLD associated with type 2 diabetes: A meta-analysis

Objective: To comprehensively evaluate the therapeutic efficacy of pioglitazone and SGLT2 inhibitors (SGLT2i) in patients with MASLD and Type 2 Diabetes(T2DM). Methods: Electronic databases, including Web of Science, PubMed, the Cochrane Library, China National Knowledge Internet (CNKI), Wan-Fang Digital Database, and China Science and Technology Journal Database (VIP) were searched from inception to December 2024. Two reviewers independently assessed study eligibility, performed continuous data extraction, and independently evaluated bias risks. Liver ultrasonography, computed tomography (CT), and biochemical indices were utilized to determine the impact of treatment in both groups. Improvement in liver biomarkers and fibrosis as primary outcome indicators; Improvement in body composition, metabolic parameters, glucose parameters, and incidence of adverse effects as a secondary outcome indicator. For continuous variables, mean and standard deviation (SD) were extracted. RevMan 5.4 software was used to systematically analyze the literature, including heterogeneity testing, odds ratios (OR) calculation, and 95 % confidence intervals (CI) for each influencing factor. Results: Nine randomly controlled trials with 755 Asian participants were included. Our research showed that SGLT2i was more effective than pioglitazone in improving fibrosis-4 score (SMD 0.41 [95%CI 0.18,0.64] p = 0.005), visceral fat area (SMD 0.34 [95%CI 0.14,0.54] p = 0.0007), BMI (SMD 0.29 [95%CI 0.03,0.56] p = 0.03), and low-density lipoprotein levels (SMD 0.21 [95%CI 0.04,0.38] p = 0.01). In contrast, no statistically significant differences were observed in other outcomes. Conclusions: Our study demonstrated that in patients with MASLD and T2DM, SGLT2i was more effective overall in improving liver fibrosis, blood lipids, liver fat, and body composition in the short term. These findings establish a theoretical basis for safe and rational drug use in clinical practice. Additionally, they may contribute to new insights into the pathogenesis of MASLD and type 2 diabetes and drug discovery and development efforts.