Peroxisome proliferator-activated receptor (PPAR) agonists improve key biomarkers of liver health in patients with primary biliary cholangitis (PBC), according to a recent analysis of several clinical trials. Findings were published in the International Journal of Hepatology.
PPAR agonists work by binding to receptors that regulate metabolism and energy use throughout the body. In the liver, these drugs help manage inflammation and control how the organ uses fatty acids. PPAR agonists include fenofibrate, seladelpar and elafibranor, among others.
To better understand the effectiveness of PPAR agonists in PBC, the authors analyzed eight clinical trials of PPAR agonists. The studies were published between 2004 and 2023 and included a total of 515 individuals with PBC.
PPARs include three subtypes: PPARα, PPARγ and PPARδ. Agonists may target any or all of these types. The analysis demonstrated that selective PPAR agonists, which target a specific PPAR, and multi-agonists, which act on multiple subtypes, both reduced alkaline phosphatase (ALP) levels. ALP is a biochemical marker of cholestasis (slow or blocked bile flow).
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Additionally, compared to those receiving a placebo, patients taking PPAR agonists had lower levels of gamma-glutamyl transferase (GGT), total bilirubin and triglycerides, which are all measures of liver health.
Levels of alanine transaminase (ALT) and aspartate aminotransferase (AST) did not differ between patients who received PPAR agonists and those who received a placebo.
Currently, ursodeoxycholic acid is the primary treatment for individuals with PBC. However, upwards of 40% of individuals do not respond to ursodeoxycholic acid, the researchers stated. Obeticholic acid (OCA), the first second-line therapy approved for PBC, was taken off the U.S. market in September 2025 due to safety concerns.
These findings highlight the potential of PPAR agonists as a viable treatment option for patients with PBC who may not respond to the first-line treatment. “Further research is necessary to fully understand the therapeutic potential and optimize the clinical use of PPAR agonists in managing PBC,” the authors concluded.
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