TY - JOUR
T1 - Review article
T2 - role of glucagon-like peptide-1 receptor agonists in non-alcoholic steatohepatitis, obesity and diabetes—what hepatologists need to know
AU - Barritt, A. Sidney
AU - Marshman, Emma
AU - Noureddin, Mazen
N1 - Funding Information:
This article was supported by Novo Nordisk Inc., who performed a medical accuracy review. Writing support was provided by Emma Marshman, a contract writer working on behalf of Axis, a division of Spirit Medical Communications Group Limited, and was funded by Novo Nordisk Inc. in accordance with Good Publication Practice 3 (GPP3) guidelines ( www.ismpp.org/gpp3 ). Emma Marshman and Laura Ward, a former employee of Axis, a division of Spirit Medical Communications Group Limited, performed the literature review, funded by Novo Nordisk Inc. Funding information
Funding Information:
This article was supported by Novo Nordisk Inc., who performed a medical accuracy review. Writing support was provided by Emma Marshman, a contract writer working on behalf of Axis, a division of Spirit Medical Communications Group Limited, and was funded by Novo Nordisk Inc. in accordance with Good Publication Practice 3 (GPP3) guidelines (www.ismpp.org/gpp3). Emma Marshman and Laura Ward, a former employee of Axis, a division of Spirit Medical Communications Group Limited, performed the literature review, funded by Novo Nordisk Inc. Declaration of personal interests: A. Sidney Barritt 4th conducts NASH-related clinical trials with support from Intercept, Genfit, Allergan, Celgene, Galmed, Pfizer, Bristol Myers Squibb, Viking and Gilead. He has provided consulting for Intercept and Target RWE in the past 12 months. Emma Marshman received funding from Novo Nordisk Inc. for medical writing support for this manuscript. Mazen Noureddin has served on the advisory boards for 89BIO, Gilead, Intercept, Pfizer, Novo Nordisk, Blade, EchoSens, Fractyl, Terns, Perspectum, Siemens and Roche Diagnostic. He has received research support from Allergan, Bristol Myers Squibb, Gilead, Galmed, Galectin, Genfit, Conatus, Enanta, Madrigal, Novartis, Shire, Viking and Zydus. He is a minor shareholder and has stocks in Anaetos, Rivus Pharma and Viking.
Publisher Copyright:
© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.
PY - 2022/4
Y1 - 2022/4
N2 - Background: Non-alcoholic steatohepatitis (NASH) 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 (GLP-1RAs) 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.
AB - Background: Non-alcoholic steatohepatitis (NASH) 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 (GLP-1RAs) 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.
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U2 - 10.1111/apt.16794
DO - 10.1111/apt.16794
M3 - Review article
C2 - 35266164
AN - SCOPUS:85125946198
SN - 0269-2813
VL - 55
SP - 944
EP - 959
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 8
ER -