The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis.
Humans
Male
Female
Middle Aged
Chalcones
/ therapeutic use
Fatty Liver
/ drug therapy
Liver
/ drug effects
Peroxisome Proliferator-Activated Receptors
/ agonists
Aged
Blood Glucose
/ metabolism
Cardiovascular Diseases
/ drug therapy
Adult
Blood Pressure
/ drug effects
Triglycerides
/ blood
Insulin Resistance
Adiponectin
/ metabolism
Lipid Metabolism
/ drug effects
Propionates
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
10 May 2024
10 May 2024
Historique:
received:
12
10
2023
accepted:
16
04
2024
medline:
11
5
2024
pubmed:
11
5
2024
entrez:
10
5
2024
Statut:
epublish
Résumé
Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary and exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid and glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging and histological grading) for all patients of the original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting glucose (FG), hs-CRP, ferritin, diastolic BP and steatosis improved significantly, independent of diabetes status: most patients with prediabetes returned to normal FG levels. Significant adiponectin increases correlated with hepatic and CMH marker improvement; patients had an average weight gain of 2.5 kg, with 49% gaining ≥2.5% weight. Therapeutic benefits were similar regardless of weight change. Here, we show that effects of lanifibranor on liver histology in MASH are accompanied with CMH improvement, indicative of potential cardiovascular clinical benefits.
Identifiants
pubmed: 38730247
doi: 10.1038/s41467-024-47919-9
pii: 10.1038/s41467-024-47919-9
doi:
Substances chimiques
Chalcones
0
Peroxisome Proliferator-Activated Receptors
0
2-(2,6-dimethyl-4-(3-(4-(methylthio)phenyl)-3-oxo-1-propenyl)phenoxyl)-2-methylpropanoic acid
0
Blood Glucose
0
Triglycerides
0
Adiponectin
0
Propionates
0
Banques de données
ClinicalTrials.gov
['NCT03008070']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
3962Informations de copyright
© 2024. The Author(s).
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