Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, China.
School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, China.
Front Endocrinol (Lausanne). 2022 Dec 7;13:1043789. doi: 10.3389/fendo.2022.1043789. eCollection 2022.
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.
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.
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%.
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.
胰高血糖素样肽-1 受体激动剂 (GLP-1 RA) 在改善血糖控制方面具有显著的临床效果。然而，关于不同 GLP-1 RA 之间胃肠道不良事件 (AE) 差异的真实世界数据仍然缺乏。本研究旨在基于真实世界数据，描述和比较不同市售 GLP-1 RA（艾塞那肽、利拉鲁肽、度拉糖肽、利司那肽和司美格鲁肽）的胃肠道 AE。
使用比例失衡分析评估 GLP-1 RA 与胃肠道不良事件之间的关联性。数据从 2018 年 1 月至 2022 年 9 月期间的美国 FDA 不良事件报告系统 (FAERS) 数据库中提取。进一步分析 GLP-1 RA 相关胃肠道 AE 的临床特征、发病时间和严重程度比例。
在 81752 份不良事件报告中，共分析了 21281 份胃肠道毒性报告，纳入患者的中位年龄为 62（四分位距 [IQR] 54-70）岁。总体而言，GLP-1 RA 与胃肠道系统疾病的风险增加相关（比值比 [OR]，1.46；95%置信区间 [CI]，1.44-1.49），这归因于利拉鲁肽（OR，2.39；95%CI，2.28-2.51）、度拉糖肽（OR，1.39；95%CI，1.36-1.42）和司美格鲁肽（OR，3.00；95%CI，2.89-3.11）。标签中发现的不良反应包括胃食管反流病、胃炎、胃石、口臭、腹腔内血肿等。此外，观察到司美格鲁肽引起恶心的风险最大（OR，7.41；95%CI，7.10-7.74）、腹泻（OR，3.55；95%CI，3.35-3.77）、呕吐（OR，6.67；95%CI，6.32-7.05）和便秘（OR，6.17；95%CI，5.72-6.66）；利拉鲁肽引起上腹痛的风险最大（OR，4.63；95%CI，4.12-5.21）和胰腺炎（OR，32.67；95%CI，29.44-36.25）。大多数胃肠道 AE 倾向于在一个月内发生。利拉鲁肽胃肠道 AE 的严重率最高（23.31%），而度拉糖肽的严重率最低，为 12.29%。
GLP-1 RA 与胃肠道 AE 显著相关，这种关联归因于利拉鲁肽、度拉糖肽和司美格鲁肽。此外，司美格鲁肽引起恶心、腹泻、呕吐、便秘和胰腺炎的风险最大，而利拉鲁肽引起上腹痛的风险最大。本研究为选择合适的 GLP-1 RA 以避免 GLP-1 RA 引起的胃肠道 AE 提供了有价值的证据。
