Future Perspectives on GLP-1 Receptor Agonists and GLP-1/glucagon Receptor Co-agonists in the Treatment of NAFLD
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Along the obesity pandemic, the prevalence of non-alcoholic fatty liver disease (NAFLD), often regarded as the hepatic manifestation of the metabolic syndrome, increases worldwide representing now the prevalent liver disease in western countries. No pharmacotherapy is approved for the treatment of NAFLD and, currently, the cornerstone treatment is lifestyle modifications focusing on bodyweight loss, notoriously difficult to obtain and even more difficult to maintain. Thus, novel therapeutic approaches are highly demanded. Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are approved for the treatment of type 2 diabetes and obesity. They exert their body weight-lowering effect by reducing satiety and food intake. GLP-1RAs have also been shown to reduce liver inflammation and fibrosis. Furthermore, glucagon receptor agonism is being investigated for the treatment of NAFLD due to its appetite and food intake-reducing effects, as well as its ability to increase lipid oxidation and thermogenesis. Recent studies suggest that glucagon receptor signaling is disrupted in NAFLD, indicating that supra-physiological glucagon receptor agonism might represent a new NAFLD treatment target. The present review provides (1) an overview in the pathophysiology of NAFLD, including the potential involvement of GLP-1 and glucagon, (2) an introduction to the currently available GLP-1RAs and (3) outlines the potential of emerging GLP-1RAs and GLP-1/glucagon receptor co-agonists in the treatment of NAFLD.
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GLP‐1 and glucagon receptor co‐agonists have been successfully used in preclinical studies for metabolic diseases.
“More recently, GLP‐1 and glucagon receptor co‐agonists have been successfully used in preclinical studies for metabolic diseases 158, but additional research is necessary to demonstrate their efficacy in humans.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [158]
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- Authors
- Seghieri, M., Christensen, A. S., Andersen, A., Solini, A., Knop, F. K., & Vilsbøll, T.
- Affiliations
- University of Pisa (IT)
- University of Copenhagen (DK)
- Corresponding author
- Vilsbøll, Tina
- ORCID
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2018-11-06
- Volume
- 9
- Pages
- 649-649
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC6232120
- OpenAlex
- W2899627734
- Cited by
- 92
- References
- 82
- Citations by year
- 2026: 8 · 2025: 6 · 2024: 9 · 2023: 16 · 2022: 8 · 2021: 19 · 2020: 18 · 2019: 7 · 2017: 1
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Steno Diabetes Center Copenhagen (SDCC 3.F CMP)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- non-alcoholic fatty liver disease, GLP-1 receptor agonists, glucagon receptor agonist, obesity, metabolic syndrome, weight loss, satiety, liver fibrosis, liver inflammation, lipid oxidation, thermogenesis, GLP-1 signaling
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