The future of incretins in the treatment of obesity and non-alcoholic fatty liver disease
Open accessAbstract
In the last few decades, glucagon-like peptide-1 receptor (GLP-1R) agonists have changed current guidelines and improved outcomes for individuals with type 2 diabetes. However, the dual glucose-dependent insulinotropic polypeptide receptor (GIPR)/GLP-1R agonist, tirzepatide, has demonstrated superior efficacy regarding improvements in HbA 1c and body weight in people with type 2 diabetes. This has led to increasing scientific interest in incretin hormones and incretin interactions, and several compounds based on dual- and multi-agonists are now being investigated for the treatment of metabolic diseases. Herein, we highlight the key scientific advances in utilising incretins for the treatment of obesity and, potentially, non-alcoholic fatty liver disease (NAFLD). The development of multi-agonists with multi-organ targets may alter the natural history of these diseases.
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GLP-1RAs have potential benefits in the treatment of NAFLD, NASH, and type 2 diabetes mellitus by regulating appetite, insulin secretion, and lipid metabolism.
“By regulating appetite, insulin secretion, and lipid metabolism, GLP-1RAs have potential benefits in the treatment of NAFLD, NASH, and T2DM.130,492,493”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [492]
The sections “Incretin hormones in the regulation of body weight” and “Incretins: a potential therapy in NAFLD” support GLP-1R agonists’ effects on appetite, their use in type 2 diabetes, and their potential for NAFLD/NASH. The NAFLD section discusses insulin-related hepatic effects, but attributes the stated improvements in lipid metabolism specifically to dual and triple agonists, not GLP-1R agonists alone. Page numbers are unavailable in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIncretin hormone-based drugs, first and foremost GLP-1RA, have emerged as a pivotal treatment option for managing both obesity and type 2 diabetes.
“Among these, incretin hormone‐based drugs, first and foremost glucagon‐like peptide 1 receptor agonists (GLP‐1RA), 11 have emerged as a pivotal treatment option for managing both obesity and T2D. 12 , 13 , 14 , 15”
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References 99 · Cited by 44
Research works printed but not linked: 3
- [30]30. Pi-Sunyer X, Astrup A, Fujioka K et al (2015) A randomized, con- trolled trial of 30 mg of liraglutide in weight management. N Engl J Med 373(1):11-22. https:// doi. org/ 10. 1056/ NEJMo a1411 892
- [48]48. Amgen (2022) Amgen presents new AMG 133 Phase 1 clini- cal data at WCIRDC 2022. Available from: www. amgen. com/ newsr oom/ press-relea ses/ 2022/ 12/ amgen-prese nts-new-amg- 133-phase-1-clini cal-data-at-wcirdc-2022. Accessed: 2 March 2023
- [101]101. Juluri R, Vuppalanchi R, Olson J et al (2011) Generalizability of the NASH CRN histological scoring system for nonalcoholic fatty liver disease. J Clin Gastroenterol 45(1):55-58. https:// doi. org/ 10. 1097/ MCG. 0B013 E3181 DD1348
- Authors
- Andreasen, C. R., Andersen, A., & Vilsbøll, T.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Vilsbøll, Tina
- Venue
- Diabetologia
- Published
- 2023-07-27
- Volume
- 66
- Issue
- 10
- Pages
- 1846-1858
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W4385295951
- Cited by
- 44
- References
- 99
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 16 · 2023: 6
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- Funders
- Steno Diabetes Center Copenhagen (SDCC 3.F CMP)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- incretins, GLP-1 receptor agonists, GIP receptor, tirzepatide, obesity, non-alcoholic fatty liver disease, type 2 diabetes, weight loss, HbA1c
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Diabetes Mellitus, Type 2, Gastric Inhibitory Polypeptide, Humans, Obesity, Glucagon-Like Peptide 1, Incretins, Non-alcoholic Fatty Liver Disease
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