AUTHOR=Tang Gang , Zhang Jie , Zhang Linyu , Xia Lingying , Tang Xiaojuan , Chen Rui , Zhou Rongxing TITLE=Efficacy and safety of peroxisome proliferator-activated receptor agonists for the treatment of primary biliary cholangitis: a meta-analysis of randomized controlled trials JOURNAL=Frontiers in Pharmacology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1432814 DOI=10.3389/fphar.2024.1432814 ISSN=1663-9812 ABSTRACT=Background

Peroxisome proliferator-activated receptor (PPAR) agonists are recognised as a promising treatment for primary biliary cholangitis (PBC). However, the effects and safety of these agonists on PBC remain unexplored. Our study aimed to investigate the efficacy and safety of PPAR agonists in treating PBC.

Methods

We searched Cochrane Library, and Web of Science, PubMed, and Embase databases from inception to 15 March 2024 for randomised controlled studies (RCTs) that enrolled individuals with PBC treated with PPAR agonists compared with placebo. The primary outcomes were biochemical response and normalization of the alkaline phosphatase (ALP) level.

Results

Eight RCTs involving 869 participants in total were included. The meta-analysis revealed that compared to placebo, PPAR agonists increased the rate of biochemical response (RR: 5.53; 95% CI: 3.79, 8.06) and normalization of the ALP level (RR: 17.18; 95% CI: 5.61, 52.61). In addition, PPAR agonists can also reduce alanine aminotransferase (ALT) (MD: −12.69 U/L; 95% CI: −18.03, −7.35), aspartate aminotransferase (AST) (MD: −4.18 U/L; 95% CI: −7.28, −1.08), ALP (MD: −142.95 U/L; 95% CI: −167.29, −118.60), γ-glutamyltransferase (GGT) (MD: −63.03 U/L; 95% CI: −92.08, −33.98), and total cholesterol (TC) levels (SMD: −0.71; 95% CI: −1.38, −0.04), and there was no significant difference in overall adverse reactions (RR: 0.99; 95% CI: 0.92, 1.05), serious adverse reactions (RR: 1.10; 95% CI: 0.70, 1.72) between the two groups.

Conclusion

PPAR agonists are safe and well-tolerated in patients with PBC and are effective in improving the rate of biochemical response and related biomarkers.