Difference in Gastrointestinal Risk Associated with Use of GLP-1 Receptor Agonists: A Real-World Pharmacovigilance Study
Open accessAbstract
BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are promising weight-loss drugs, but real-world data concerning the liability of GLP-1RAs in gastrointestinal safety are lacking. We examined the differences in gastrointestinal safety between semaglutide and liraglutide. MATERIALS AND METHODS: We used the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database and retrieved data during the first three years of semaglutide and liraglutide approved by the FDA. Thirteen main gastrointestinal adverse drug reactions (GADRs) were evaluated. Patient demographics, treatment information, and outcome of events were summarized. Disproportionality analyses were conducted by estimating the reporting odds ratios (RORs) and 95% confidence intervals (CIs). RESULTS: In the reported cases of semaglutide (n = 2047) and liraglutide (n = 4175), semaglutide had a higher pooled ROR and later pooled time-to-onset median of GADRs compared with those of liraglutide (5.53, 95% CI 5.23-5.85 vs 3.95, 95% CI 3.81-4.10; 7 days, Q1-Q3: 0-48 vs 4 days, Q1-Q3: 0-34.5). The thirteen GADRs associated with these two GLP-1RAs showed a significant difference in the profile of reporting risk and time-to-onset. CONCLUSION: GLP-1RAs produce a spectrum of distinct classes of GADRs. The individual properties of GADRs between semaglutide and liraglutide might enable incretin-based treatment of obesity to be "tailored" to the needs of each patient.
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These findings are in line with recent reports highlighting semaglutide's association with multiple gastrointestinal disturbances.
“These findings are in line with recent reports highlighting semaglutide’s association with multiple GI disturbances [58].”
From Gastrointestinal adverse events associated with GLP-1 RA in non-diabetic patients with overweight or obesity: a systematic review and network meta-analysis (2025) · cites this paper as [58]
Discontinuations due to abdominal pain were reported in three publications and ranged from 0 to 1.4% (placebo-adjusted).
“Discontinuations due to abdominal pain were reported in three publications [12,36,104] and ranged from 0 to 1.4% (placebo-adjusted).”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [104]
In one RWE study using the FAERS database, the incidence of other serious AEs was 9.5% for liraglutide and 17.6% for semaglutide.
“In one RWE study using the FAERS database, the incidence of other serious AEs was 9.5% and 17.6% for liraglutide and semaglutide, respectively [104].”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [104]
SAEs occurring in >5% of patients were reported in 26 studies, with 9 publications reporting SAEs in >10% of patients.
“SAEs occurring in >5% of patients were reported in 26 studies [11][12][13][14]35,40,42,51,52,58,62,63,[65][66][67]70,74,77,[84][85][86]93,94,96,103,104], with 9 publications reporting SAEs in >10% of patients [11,14,66,67,85,86,89,103,104].”
From Symptomatic Adverse Events and Quality of Life Related to Incretin-Based Medicines for Obesity: A Systematic Review Involving >400,000 Subjects (2025) · cites this paper as [104]
A previous study reported only 13 semaglutide-associated gastrointestinal adverse events from the FAERS database in 2018-2020.
“In a previous study, only 13 semaglutide-associated gastrointestinal AEs were reported in 2018–2020 from the FAERS database (13)”
From Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system (2022) · cites this paper as [13]
The serious outcomes of gastrointestinal adverse events had not been reported and compared.
“The serious outcomes of gastrointestinal AEs had not been reported and compared.”
From Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system (2022) · cites this paper as [13]
A previous real-world disproportionality analysis of GLP-1 receptor agonist-associated gastrointestinal adverse events based on FAERS from 2018 to 2020 included 2,047 cases of semaglutide and 4,075 cases of liraglutide for the treatment of obesity.
“Another previous real-world disproportionality analysis of GLP-1RAs-associated gastrointestinal AEs based on the FDA Adverse Event Reporting System (FAERS) from 2018 to 2020 included 2,047 cases of semaglutide and 4,075 cases of liraglutide for the treatment of obesity (13).”
From Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system (2022) · cites this paper as [13]
The previous study demonstrated that semaglutide had a higher pooled reporting odds ratio and later pooled time-to-onset median of gastrointestinal adverse events compared with liraglutide.
“This study demonstrated that semaglutide had a higher pooled ROR and later pooled time-to-onset median of gastrointestinal AEs compared with those of liraglutide.”
From Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system (2022) · cites this paper as [13]
A real-world pharmacovigilance study of semaglutide demonstrated a pooled median time-to-onset of gastrointestinal adverse events of 7 days (IQR 0-48 days).
“A real-world pharmacovigilance study of semaglutide had also demonstrated a similar pooled median time-to-onset of gastrointestinal AEs (7 days, IQR 0–48 days), which further supported the findings of our analysis (13).”
From Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system (2022) · cites this paper as [13]
Gastrointestinal risks in type 2 diabetes mellitus occurred more often in females (52.32%).
“which was in line with the finding that gastrointestinal risks in T2DM occurred more often in females (52.32%) (13).”
From Gastrointestinal adverse events associated with semaglutide: A pharmacovigilance study based on FDA adverse event reporting system (2022) · cites this paper as [13]
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References 33 · Cited by 46
- Authors
- Zhou, Y., Chen, M., Liu, L., & Chen, Z.
- Affiliations
- Fujian Medical University (CN)
- Union Hospital (CN)
- Corresponding author
- Chen, Zhou
- Venue
- Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
- Publisher
- Informa UK Limited
- Published
- 2022-01
- Volume
- Volume 15
- Pages
- 155-163
- ISSN
- 1178-7007 (ISSN-L)
- PMC
- PMC8763271
- OpenAlex
- W4205591291
- Cited by
- 46
- References
- 33
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 18 · 2023: 3 · 2022: 4
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Diabetes Metabolic Syndrome and Obesity (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- Fujian Medical University (XRCZX2020003)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- GLP-1 receptor agonists, semaglutide, liraglutide, gastrointestinal adverse effects, pharmacovigilance, obesity treatment, reporting odds ratio, time to onset, FDA Adverse Event Reporting System
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