PPAR-alpha/gamma agonists, glucagon-like peptide-1 receptor agonists and metformin for non-alcoholic fatty liver disease: A network meta-analysis

Abstract

Objective To undertake a network meta-analysis to compare the relative efficacy of a dual peroxisome proliferator-activated receptor (PPAR)α and PPARγ agonist, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin in patients with non-alcoholic fatty liver disease (NAFLD). Methods Electronic databases, including Embase®, PubMed® and The Cochrane Library, were searched systematically for eligible studies from inception to 20 July 2022. Randomized controlled trials (RCTs) that investigated aspartate aminotransferase, alanine aminotransferase (ALT) and triglyceride levels were considered for inclusion. Data were extracted using a standardized data collection table. A network meta-analysis was performed. Relative risk and 95% confidence interval were calculated for continuous data and I2 was used to assess the heterogeneity of studies. Results A total of 22 RCTs involving 1698 patients were eligible for inclusion in the analysis. Both direct analysis and indirect analysis showed that saroglitazar was significantly superior to GLP-1RAs in improving ALT levels. Metformin improved ALT levels, but the effect was not as good as saroglitazar. Conclusion Saroglizatar was the most effective drug for improving NAFLD. INPLASY registration number: INPLASY202340066

The role of neuroinflammation in neurodegenerative diseases: current understanding and future therapeutic targets

“…However, GM-CSF has been controversial in treating ALS with mixed clinical findings showing that GM-CSF might not be important to ALS patients or at least not slow down the disease process (Mortada et al, 2021). Other drugs targeting PPAR-γ and GLP-1 have also been described for their neuroprotective and anti-neuroinflammatory actions besides GM-CSF (Zhang Z. et al, 2023). Modern research suggests that molecules might relieve AD and PD symptoms, by restoring Akt-1 and mTOR, and insulin Pathways in the brain.…”

Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases

“…The exploration of thyromimetics, which mimic thyroid hormone actions to regulate metabolism, demonstrates potential in ameliorating MASH-related liver damage, inflammation, and fibrosis, as evidenced by clinical trials with agents like resmetirom ( Sinha et al, 2020 ). Similarly, agents targeting metabolic pathways, such as GLP-1 receptor agonists and PPARα agonists, are under investigation for their capacity to correct metabolic abnormalities integral to MASH pathophysiology ( Zhu et al, 2021 ; Zhang et al, 2023 ). Moreover, the complex interplay between MASH and gut microbiota suggests that modulating the gut microbiome through probiotics, prebiotics, or faecal microbiota transplantation could offer a novel avenue for treatment, addressing dysbiosis and its contributions to liver inflammation and damage ( Xiang et al, 2022 ; Solanki et al, 2023 ).…”

Current Clinical Trial Status and Future Prospects of PPAR-Targeted Drugs for Treating Nonalcoholic Fatty Liver Disease

“…A recent meta-analysis of ten clinical studies demonstrated that the treatment with saroglitazar (4 mg/day; either monotherapy or in combination) could significantly improve liver enzyme levels, reduce liver stiffness, and improve metabolic parameters (serum glucose and lipid profile) in patients with NAFLD or NASH [ 54 ]. Another recent network meta-analysis of 22 randomized controlled studies revealed that saroglitazar was significantly superior to the GLP-1 receptor agonists, including semaglutide, in improving ALT levels [ 55 ]. Overall, saroglitazar may be equal to or more effective than semaglutide for treating NASH.…”