{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T07:04:19Z","timestamp":1793689459409,"version":"4.5.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:00:00Z","timestamp":1670371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073921"],"award-info":[{"award-number":["82073921"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have significantly improved clinical effects on glycemic control. However, real-world data concerning the difference in gastrointestinal adverse events (AEs) among different GLP-1 RAs are still lacking. Our study aimed to characterize and compare gastrointestinal AEs among different marketed GLP-1 RAs (exenatide, liraglutide, dulaglutide, lixisenatide, and semaglutide) based on real-world data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Disproportionality analysis was used to evaluate the association between GLP-1 RAs and gastrointestinal adverse events. Data were extracted from the US FDA Adverse Event Reporting System (FAERS) database between January 2018 and September 2022. Clinical characteristics, the time-to-onset, and the severe proportion of GLP-1 RAs-associated gastrointestinal AEs were further analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 21,281 reports of gastrointestinal toxicity were analyzed out of 81,752 adverse event reports, and the median age of the included patients was 62 (interquartile range [IQR] 54\u201370) years old. Overall GLP-1 RAs were associated with increased risk of gastrointestinal system disorders (ROR, 1.46; 95% CI, 1.44\u20131.49), which were further attributed to liraglutide (ROR, 2.39; 95% CI, 2.28\u20132.51), dulaglutide (ROR, 1.39; 95% CI, 1.36-1.42), and semaglutide (ROR, 3.00; 95% CI, 2.89\u20133.11). Adverse events uncovered in the labels included gastroesophageal reflux disease, gastritis, bezoar, breath odor, intra-abdominal hematoma, etc. Furthermore, it was observed that semaglutide had the greatest risk of nausea (ROR, 7.41; 95% CI, 7.10\u20137.74), diarrhea (ROR, 3.55; 95% CI, 3.35\u20133.77), vomiting (ROR, 6.67; 95% CI, 6.32\u20137.05), and constipation (ROR, 6.17; 95% CI, 5.72\u20136.66); liraglutide had the greatest risk of abdominal pain upper (ROR, 4.63; 95% CI, 4.12\u20135.21) and pancreatitis (ROR, 32.67; 95% CI, 29.44\u201336.25). Most gastrointestinal AEs tended to occur within one month. Liraglutide had the highest severe rate of gastrointestinal AEs (23.31%), while dulaglutide had the lowest, with a severe rate of 12.29%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>GLP-1 RA were significantly associated with gastrointestinal AEs, and the association was further attributed to liraglutide, dulaglutide, and semaglutide. In addition, semaglutide had the greatest risk of nausea, diarrhea, vomiting, constipation, and pancreatitis, while liraglutide had the greatest risk of upper abdominal pain. Our study provided valuable evidence for selecting appropriate GLP-1 RAs to avoid the occurrence of GLP-1 RA-induced gastrointestinal AEs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2022.1043789","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T00:07:54Z","timestamp":1670371674000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":252,"title":["Association between different GLP-1 receptor agonists and gastrointestinal adverse reactions: A real-world disproportionality study based on FDA adverse event reporting system database"],"prefix":"10.3389","volume":"13","author":[{"given":"Lulu","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119","article-title":"Idf diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res Clin Pract"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2020.101102","article-title":"Glp-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-Art","volume":"46","author":"Nauck","year":"2021","journal-title":"Mol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1136\/postgradmedj-2019-137186","article-title":"An overview of glp-1 agonists and recent cardiovascular outcomes trials","volume":"96","author":"Sheahan","year":"2020","journal-title":"Postgrad Med J"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4103\/2230-8210.111625","article-title":"Glucagon-like peptide-1 analogues: An overview","volume":"17","author":"Gupta","year":"2013","journal-title":"Indian J Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(06)69705-5","article-title":"The incretin system: Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes","volume":"368","author":"Drucker","year":"2006","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14202","article-title":"Gastrointestinal adverse events with insulin Glargine\/Lixisenatide fixed-ratio combination versus glucagon-like peptide-1 receptor agonists in people with type 2 diabetes mellitus: A network meta-analysis","volume":"23","author":"Rayner","year":"2021","journal-title":"Diabetes Obes Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12872","article-title":"Upper and\/or lower gastrointestinal adverse events with glucagon-like peptide-1 receptor agonists: Incidence and consequences","volume":"19","author":"Horowitz","year":"2017","journal-title":"Diabetes Obes Metab"},{"key":"B8","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1089\/dia.2014.0188","article-title":"Gastrointestinal adverse events of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: A systematic review and network meta-analysis","volume":"17","author":"Sun","year":"2015","journal-title":"Diabetes Technol Ther"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12824","article-title":"Occurrence of nausea, vomiting and diarrhoea reported as adverse events in clinical trials studying glucagon-like peptide-1 receptor agonists: A systematic analysis of published clinical trials","volume":"19","author":"Bettge","year":"2017","journal-title":"Diabetes Obes Metab"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2022.102511","article-title":"Semaglutide for the treatment of type 2 diabetes mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes","volume":"16","author":"Zaazouee","year":"2022","journal-title":"Diabetes Metab Syndr"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1016\/j.clinthera.2017.07.036","article-title":"Gastrointestinal adverse events of dipeptidyl peptidase 4 inhibitors in type 2 diabetes: A systematic review and network meta-analysis","volume":"39","author":"Wu","year":"2017","journal-title":"Clin Ther"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.15386\/cjmed-804","article-title":"Acute pancreatitis during glp-1 receptor agonist treatment. 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