Liraglutide and semaglutide led to histological resolution of in ~40% to 60% of patients.
GLP-1 receptor agonists significantly lower glucose levels and promote body weight loss in large trials involving type 2 diabetes.
In individuals with obesity without type 2 diabetes, liraglutide and semaglutide are associated with sustained body weight reduction.
Liraglutide reduced metabolic dysfunction, insulin resistance, and lipotoxicity in a phase II trial focused on NASH.
Statistically significant effects of GLP-1 receptor agonists on fibrosis in NASH have not been confirmed.
Gastrointestinal and gallbladder-related adverse events are associated with GLP-1 receptor agonists, possibly linked to weight loss.
Meta-analyses show no increased risk of acute pancreatitis, pancreatic cancer, or other malignancies with GLP-1 receptor agonists.
Simplified
BACKGROUND: Non-alcoholic steatohepatitis () is characterised by hepatic lipid accumulation, cell injury, inflammation and fibrosis. Insulin resistance, a hallmark of type 2 diabetes (T2D) and obesity, is a key pathogenic driver of NASH. Other than difficult-to-maintain lifestyle changes, there are no approved treatments for NASH. Due to their effects on multiple pathophysiological processes, glucagon-like peptide-1 receptor agonists () have been tested in disorders related to insulin resistance and metabolic defects.
AIMS: To summarise studies of GLP-1RAs relevant to the treatment of NASH.
METHODS: PubMed searches were performed and results were compiled.
RESULTS: Large trials with GLP-1RAs in T2D demonstrate highly effective glucose lowering, with body weight loss, and in some cases, reduced cardiovascular events and improved liver transaminases. The GLP-1RAs, liraglutide and semaglutide, were associated with clinically relevant, sustained body weight reduction in individuals with overweight or obesity and without T2D. In a phase II trial in NASH, liraglutide reduced metabolic dysfunction, insulin resistance and lipotoxicity in key organs associated with NASH pathogenesis. Furthermore, liraglutide and semaglutide led to histological resolution of NASH in ~40% to 60% of patients, although a statistically significant effect on fibrosis has not been confirmed. Regarding safety, GLP-1RAs are associated with gastrointestinal and gallbladder-related adverse events, with the latter perhaps related to weight loss. Meta-analyses do not indicate increased risk of acute pancreatitis, pancreatic cancer or other malignancies with GLP-1RAs.
CONCLUSIONS: These studies support the use of GLP-1RAs for the improvement of underlying metabolic dysfunction observed in NASH and suggest further long-term phase III trials are warranted.
Key numbers
39%
Resolution Rate Increase
Resolution of in patients treated with liraglutide vs. placebo.
14.9%
Weight Loss with Semaglutide
Mean percentage weight loss in adults with obesity treated with semaglutide vs. placebo.
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