Which is the optimal antiobesity agent for patients with nonalcoholic fatty liver disease?

Abstract

Nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease and affects a considerable proportion of the general population worldwide. Obesity is a major risk factor for development and progression of NAFLD and weight loss is an effective intervention for the management of NAFLD. However, few patients achieve substantial and sustained weight loss with lifestyle measures. Therefore, antiobesity agents are frequently considered in patients with NAFLD but there are limited data on their safety and efficacy. In the present review, we discuss the role of antiobesity agents in the management of NAFLD. All approved antiobesity agents appear to reduce transaminase levels and to improve steatosis in patients with NAFLD. However, their effects on fibrosis are less well studied and whether they affect liver-related outcomes, including progression to cirrhosis and hepatocellular cancer, is unknown. The glucagon-like peptide-1 receptor agonists, liraglutide and semaglutide, appear to represent a first-line option in obese patients with NAFLD and type 2 diabetes mellitus (T2DM) since they induce considerable weight loss and have been extensively studied in patients with T2DM. However, more studies are needed to evaluated their effects on liver-related and cardiovascular outcomes in patients with NAFLD, particularly in those without T2DM.

Current Therapeutical Approaches Targeting Lipid Metabolism in NAFLD

“…At the moment, though, it seems that semaglutide is not effective in resolving or ameliorating liver fibrosis once it is present [ 125 ], whereas it seems to decrease steatosis and liver inflammation in vivo in Ldrl −/− mice [ 126 ]. Comparative studies and meta-analyses are currently being carried out in order to identify the most effective drug and its posology, which seems to also vary according to the patients’ metabolic status and compliance [ 127 , 128 , 129 , 130 ].…”

Hydroxytyrosol Linoleoyl Ether Ameliorates Metabolic-Associated Fatty Liver Disease Symptoms in Obese Zucker Rats

“…8,9 The investigation for new therapeutic approaches for MAFLD starts with anti-obesity agents that induce considerable weight loss and reduction of fat tissue, with consequent beneficial effects such as the decrease in transaminase levels and hepatic steatosis. 10 Unfortunately, these types of drugs lack efficacy against the potential worsening of steatosis toward steatohepatitis followed by advanced fibrosis and progression to cirrhosis and hepatocellular cancer. Even the newly designed GLP-1 receptor agonists, which have revolutionized the treatment of obesity, are limited and insufficient to improve MAFLD.…”

“…To date, there are no pharmacological treatments effective enough that reverse or prevent the development of MAFLD, and so far, the most frequent medical indication against hepatic steatosis is the use of fibrates and a balanced diet follow-up. , The investigation for new therapeutic approaches for MAFLD starts with anti-obesity agents that induce considerable weight loss and reduction of fat tissue, with consequent beneficial effects such as the decrease in transaminase levels and hepatic steatosis . Unfortunately, these types of drugs lack efficacy against the potential worsening of steatosis toward steatohepatitis followed by advanced fibrosis and progression to cirrhosis and hepatocellular cancer.…”