PMID- 36568085 OWN - NLM STAT- MEDLINE DCOM- 20230110 LR - 20230126 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 13 DP - 2022 TI - Association between different GLP-1 receptor agonists and gastrointestinal adverse reactions: A real-world disproportionality study based on FDA adverse event reporting system database. PG - 1043789 LID - 10.3389/fendo.2022.1043789 [doi] LID - 1043789 AB - OBJECTIVE: 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. METHODS: 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. RESULTS: 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] 54-70) years old. Overall GLP-1 RAs were associated with increased risk of gastrointestinal system disorders (ROR, 1.46; 95% CI, 1.44-1.49), which were further attributed to liraglutide (ROR, 2.39; 95% CI, 2.28-2.51), dulaglutide (ROR, 1.39; 95% CI, 1.36-1.42), and semaglutide (ROR, 3.00; 95% CI, 2.89-3.11). 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, 7.10-7.74), diarrhea (ROR, 3.55; 95% CI, 3.35-3.77), vomiting (ROR, 6.67; 95% CI, 6.32-7.05), and constipation (ROR, 6.17; 95% CI, 5.72-6.66); liraglutide had the greatest risk of abdominal pain upper (ROR, 4.63; 95% CI, 4.12-5.21) and pancreatitis (ROR, 32.67; 95% CI, 29.44-36.25). 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%. CONCLUSION: 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. CI - Copyright (c) 2022 Liu, Chen, Wang, Chen and Chen. FAU - Liu, Lulu AU - Liu L AD - Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China. AD - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China. FAU - Chen, Jia AU - Chen J AD - Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China. AD - Department of Pharmacy, Sichuan Provincial People's Hospital Jinniu Hospital, Chengdu, China. FAU - Wang, Lei AU - Wang L AD - School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China. FAU - Chen, Chen AU - Chen C AD - West China School of Pharmacy, Sichuan University, Chengdu, China. FAU - Chen, Li AU - Chen L AD - Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China. AD - Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20221207 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 RN - 89750-14-1 (Glucagon-Like Peptide 1) RN - 0 (Glucagon-Like Peptide-1 Receptor) RN - 0 (Hypoglycemic Agents) RN - 839I73S42A (Liraglutide) SB - IM MH - Aged MH - Humans MH - Middle Aged MH - Abdominal Pain MH - Constipation/chemically induced MH - *Diabetes Mellitus, Type 2/chemically induced MH - Diarrhea/chemically induced MH - *Gastrointestinal Diseases/chemically induced/epidemiology MH - Glucagon-Like Peptide 1 MH - *Glucagon-Like Peptide-1 Receptor/agonists MH - *Hypoglycemic Agents/adverse effects MH - Liraglutide/adverse effects MH - Nausea/chemically induced MH - Pancreatitis/chemically induced MH - Vomiting/chemically induced MH - Adverse Drug Reaction Reporting Systems/statistics & numerical data MH - United States/epidemiology MH - United States Food and Drug Administration/statistics & numerical data MH - Databases, Factual/statistics & numerical data PMC - PMC9770009 OTO - NOTNLM OT - GLP-1 receptor agonists OT - adverse drug reactions OT - data mining OT - gastrointestinal toxicities OT - pharmacovigilance COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/12/27 06:00 MHDA- 2022/12/28 06:00 PMCR- 2022/01/01 CRDT- 2022/12/26 03:44 PHST- 2022/09/14 00:00 [received] PHST- 2022/11/21 00:00 [accepted] PHST- 2022/12/26 03:44 [entrez] PHST- 2022/12/27 06:00 [pubmed] PHST- 2022/12/28 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2022.1043789 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2022 Dec 7;13:1043789. doi: 10.3389/fendo.2022.1043789. eCollection 2022.