Gastrointestinal adverse events associated with GLP-1 receptor agonists in metabolic dysfunction-associated steatotic liver disease (MASLD): a systematic review and meta-analysis
Open accessAbstract
Background: Metabolic dysfunction-associated steatotic liver disease, a prevalent chronic liver condition, can cause severe complications like hepatitis, cirrhosis, and hepatocellular carcinoma. In recent years, glucagon-like peptide-1 receptor agonists (GLP - 1RA) have shown unique therapeutic advantages and may become a preferred treatment for it. This meta-analysis aims to systematically examine GLP-1RA associated adverse events, providing a basis for guiding patient clinical management. Methods: We conducted a search for randomized controlled trials (RCTs) investigating the therapeutic effects of GLP-1RA in the treatment of metabolic dysfunction-associated steatotic liver disease across four databases: PubMed, Embase, Web of Science, and Cochrane Library. The search period extended from the inception of each database until December 2023. Information pertaining to various adverse events was collected as outcome measures. Statistical analysis of the results and assessment of bias risk were conducted utilizing Review Manager (version 5.4.1) software. Results: An analysis of 10 studies encompassing 960 participants revealed a significantly higher overall incidence of adverse events in the GLP-1RA group compared to the control group (OR: 2.40 [1.10, 5.26], P = 0.03). Subgroup analysis based on treatment duration demonstrated a higher rate of adverse events in the GLP-1RA group during follow-ups of less than 30 weeks (P = 0.0005, OR: 3.58 [1.75, 7.32]), but no statistical difference was observed between the two groups in follow-ups exceeding 30 weeks. There was no statistically significant difference between the two groups in adverse events leading to discontinuation (P = 0.29, OR: 1.47 [0.72, 2.98]). However, a notable difference was observed in gastrointestinal adverse events (P < 0.00001, OR: 4.83 [3.36, 6.95]). Conclusion: GLP-1RA exhibits an overall higher incidence of adverse events in the treatment of metabolic dysfunction-associated steatotic liver disease, particularly in the gastrointestinal domain. Short-term use of GLP-1RA may be associated with a greater occurrence of adverse events, underscoring the importance of educating patients on preventive measures and establishing tolerance. However, there was no statistically significant difference between the two groups in severe adverse events and adverse events leading to discontinuation, confirming the safety profile of GLP-1RA application.
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The odds ratio for adverse GI events in individuals with metabolic dysfunction-associated steatotic liver disease using GLP-1RA versus placebo/other diabetes therapy was 4.83 (95% CI 3.36-6.95).
“The odds ratio for adverse GI events (e.g., nausea, vomiting, diarrhea, constipation) in individuals with metabolic dysfunction–associated steatotic liver disease using GLP-1RA versus placebo/other diabetes therapy was 4.83 (95% CI 3.36–6.95) (112)”
From The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications (2026) · cites this paper as [112]
Results §3.7 reports the claimed odds ratio for gastrointestinal adverse events in the GLP-1RA group versus controls: 4.83 [3.36, 6.95]. However, the included-study characteristics in Results §3.2 list a non-drug comparator as well as placebo and active treatments, so “placebo/other diabetes therapy” does not fully describe the control groups. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThere was no increased rate of adverse effects leading to discontinuation of treatment in GLP-1RA users compared with non-GLP-1RA users in that population.
“There was no increased rate of adverse effects leading to discontinuation of treatment in GLP-1RA users compared with non–GLP-1RA users (112).”
From The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications (2026) · cites this paper as [112]
Results §3.6 reports no statistically significant difference in discontinuation due to adverse events between the GLP-1RA and control groups (P = 0.29). The claim omits that uncertainty: the estimated odds ratio was 1.47, so the study does not establish that the rate was no higher. (LLM, conf=0.84)
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“There was no increased rate of adverse effects leading to discontinuation of treatment in GLP-1RA users compared with non–GLP-1RA users (112).”
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- Authors
- Huang, X., Wu, M., Huang, B., & Zhang, Y.
- Affiliations
- Fujian Medical University (CN)
- Corresponding author
- Zhang, Yi
- Venue
- Frontiers in Medicine
- Publisher
- Frontiers Media SA
- Published
- 2025-02-20
- Volume
- 12
- Pages
- 1509947-1509947
- ISSN
- 2296-858X (ISSN-L)
- PMC
- PMC11882565
- OpenAlex
- W4407798273
- Cited by
- 12
- References
- 44
- Citations by year
- 2026: 6 · 2025: 6
- FWCI
- 1.84
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Quanzhou City Science and Technology Program (2022NS066)
- 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
- GLP-1 receptor agonists, non-alcoholic fatty liver disease, gastrointestinal adverse effects, drug safety, treatment duration, drug tolerance, drug-induced liver injury, hepatotoxicity, drug-induced pancreatitis, drug-induced cholestasis, drug-induced skin reaction, drug-induced thrombocytopenia
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