The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review

Abstract

Background Non-alcoholic fatty liver disease (NAFLD) is becoming increasingly prevalent worldwide, emerging as a significant health issue on a global scale. Berberine exhibits potential for treating NAFLD, but clinical evidence remains inconclusive. This meta-analysis was conducted to assess the efficacy and safety of berberine for treating NAFLD. Methods This study was registered with PROSPERO (No. CRD42023462338). Identification of randomized controlled trials (RCTs) involved searching 6 databases covering the period from their initiation to 9 September 2023. The primary outcomes comprised liver function markers such as glutamyl transpeptidase (GGT), alanine transaminase (ALT), aspartate transaminase (AST), lipid indices including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment for insulin resistance (HOMA-IR) and body mass index (BMI). Review Manager 5.4 and STATA 17.0 were applied for analysis. Results Among 10 RCTs involving 811 patients, berberine demonstrated significant reductions in various parameters: ALT (standardized mean difference (SMD) = − 0.72), 95% confidence interval (Cl) [− 1.01, − 0.44], P < 0.00001), AST (SMD = − 0.79, 95% CI [− 1.17, − 0.40], P < 0.0001), GGT (SMD = − 0.62, 95% CI [− 0.95, − 0.29], P = 0.0002), TG (SMD = − 0.59, 95% CI [− 0.86, − 0.31], P < 0.0001), TC(SMD = − 0.74, 95% CI [− 1.00, − 0.49], P < 0.00001), LDL-C (SMD = − 0.53, 95% CI [− 0.88, − 0.18], P = 0.003), HDL-C (SMD = − 0.51, 95% CI [− 0.12, 1.15], P = 0.11), HOMA-IR (SMD = − 1.56, 95% CI [− 2.54, − 0.58], P = 0.002), and BMI (SMD = − 0.58, 95% CI [− 0.77, − 0.38], P < 0.00001). Importantly, Berberine exhibited a favorable safety profile, with only mild gastrointestinal adverse events reported. Conclusion This meta-analysis demonstrates berberine's efficacy in improving liver enzymes, lipid profile, and insulin sensitivity in NAFLD patients. These results indicate that berberine shows promise as an adjunct therapy for NAFLD. Trial registration The protocol was registered with PROSPERO (No. CRD42023462338). Registered on September 27, 2023 Graphical Abstract

NAFLD in the 21st Century: Current Knowledge Regarding Its Pathogenesis, Diagnosis and Therapeutics

“…Apart from pegozafermin and resmetiron, ZSP1601 is an investigational drug belonging to a first-in-class pan-phosphodiesterase (pan-PDE) inhibitor, which has been developed for the treatment of NASH [106]. This pan-PDE inhibitor has been suggested to decrease levels of TNF-α via its action on PDE-2, thus reducing inflammation in NASH [84]. Hu et al, in their phase 1b-2a RCT, enrolled 36 patients with NAFLD who received ZSP1601 50 mg once daily, 50 mg twice daily, 100 mg twice daily, or placebo.…”