Comparative efficacy of sodium-glucose transporter 2 inhibitors on lipid profiles in nonalcoholic fatty liver disease (NAFLD): a comprehensive Bayesian network meta-analysis.

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is a global health concern associated with dyslipidemia, obesity, and type 2 diabetes mellitus (T2DM), necessitating effective therapeutic strategies. Sodium-glucose transporter 2 (SGLT-2) inhibitors have shown promise in improving metabolic parameters, but their comparative efficacy in NAFLD remains unclear.

Methods: We systematically searched PubMed, Cochrane Library, Scopus, and Embase for randomized controlled trials (RCTs) up to 31 December 2024, involving NAFLD patients treated with SGLT-2 inhibitors versus placebo or standard treatments. Outcomes included changes in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, triglycerides, BMI, and HbA1c. A Bayesian NMA was performed using a random-effects model, with mean differences (MD) and 95% credible intervals (CrI) reported. Treatments were ranked using Surface Under the Cumulative Ranking Curve (SUCRA) scores.

Results: We evaluated and compared the efficacy of SGLT-2 inhibitors in improving lipid profiles (LDL-C, HDL-C, total cholesterol, and triglycerides), BMI, and HbA1c in patients with NAFLD. Eleven RCTs involving 805 patients were included. Empagliflozin achieved the greatest LDL-C reduction (MD: -8.07 mg/dL, 95% CrI: -25.92 to 1.41; SUCRA: 95.38%), total cholesterol reduction (MD: -15.08 mg/dL, 95% CrI: -58.87 to 5.38; SUCRA: 94.32%), and HbA1c reduction (MD: -0.69%, 95% CrI: -1.52 to -0.06; SUCRA: 81.84%). Ipragliflozin non-significantly increased HDL-C (MD: 2.28 mg/dL, 95% CrI: -1.21 to 4.83; SUCRA: 85.11%) and significantly reduced triglyceride (MD: -22.39 mg/dL, 95% CrI: -39.25 to -7.27; SUCRA: 82.26%). Dapagliflozin resulted in significant BMI reduction (MD: -1.23 kg/m², 95% CrI: -2.11 to -0.41; SUCRA: 73.28%).

Conclusion: Empagliflozin and ipragliflozin demonstrated superior efficacy in improving lipid profiles, while dapagliflozin was most effective for BMI reduction in NAFLD patients. These findings align with their cardiovascular and metabolic benefits, offering a multifaceted approach to a complex disease. Further research is needed to confirm long-term effects and optimize treatment strategies for diverse NAFLD populations.