Chiang Cho-Hung, Jaroenlapnopparat Aunchalee, Colak Sena Cakir, Yu Chun-Chiao, Xanthavanij Nutchapon, Wang Tsu-Hsien, See Xin Ya, Lo Shao-Wei, Ko Albert, Chang Yu-Cheng, Song Junmin, Hsia Yuan Ping, Chiang Cho-Han
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Digestive Health Institute, Orlando Health, Orlando, Florida.
Gastroenterology. 2025 Nov;169(6):1268-1281. doi: 10.1053/j.gastro.2025.06.003. Epub 2025 Jun 9.
BACKGROUND & AIMS: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for glycemic control or weight management in patients with type 2 diabetes mellitus or overweight/obesity. However, there are concerns regarding their association with serious gastrointestinal adverse events, although findings have been inconsistent.
We systematically searched 5 databases for placebo-controlled randomized controlled trials assessing GLP-1RAs in patients with type 2 diabetes mellitus, overweight/obesity, or metabolic dysfunction-associated steatohepatitis/metabolic dysfunction-associated steatotic liver disease. We included trials that reported cholecystitis, cholelithiasis, cholangitis, cholestasis, pancreatitis, gastroesophageal reflux disease (GERD), gastritis, esophagitis, gastrointestinal ischemia, gastrointestinal hemorrhage, intestinal obstruction, paralytic ileus, gastrointestinal ulceration, gastrointestinal perforation, or gastroparesis. Meta-analyses were performed using a random-effects model, with subgroup analyses evaluating risks based on patient population, GLP-1RA vs dual-agonist formulation, weight-loss profile, dosing, and duration of action.
We included 55 randomized controlled trials involving 106,395 participants. GLP-1RAs increased the risk of cholelithiasis (risk ratio [RR], 1.46; 95% CI, 1.09-1.97; 2 more cases per 1000) and probably increased the risk of GERD (RR, 2.19; 95% CI, 1.48-3.25; 4 more cases per 1000) compared with placebo. GLP-1RAs probably have little or no effect on the risk of other gastrointestinal or biliary events. Subgroup analyses showed that the increased risks of cholelithiasis and GERD were more pronounced in trials including individuals with overweight/obesity or metabolic dysfunction-associated steatohepatitis/metabolic dysfunction-associated steatotic liver disease, weight-loss-inducing GLP-1RAs, or high-dose formulations, although these subgroup effects were not statistically significant.
GLP-1RAs are associated with an increased risk of cholelithiasis and GERD, but do not appear to increase the risk of other gastrointestinal or biliary adverse events.
胰高血糖素样肽-1受体激动剂（GLP-1RAs）被广泛用于2型糖尿病或超重/肥胖患者的血糖控制或体重管理。然而，尽管研究结果并不一致，但人们对其与严重胃肠道不良事件的关联仍存在担忧。
我们系统检索了5个数据库，以查找评估GLP-1RAs在2型糖尿病、超重/肥胖或代谢功能障碍相关脂肪性肝炎/代谢功能障碍相关脂肪性肝病患者中应用的安慰剂对照随机对照试验。我们纳入了报告胆囊炎、胆结石、胆管炎、胆汁淤积、胰腺炎、胃食管反流病（GERD）、胃炎、食管炎、胃肠道缺血、胃肠道出血、肠梗阻、麻痹性肠梗阻、胃肠道溃疡、胃肠道穿孔或胃轻瘫的试验。采用随机效应模型进行荟萃分析，并进行亚组分析，根据患者人群、GLP-1RA与双激动剂剂型、减肥效果、给药剂量和作用持续时间评估风险。
我们纳入了55项随机对照试验，涉及106395名参与者。与安慰剂相比，GLP-1RAs增加了胆结石风险（风险比[RR]，1.46；95%置信区间[CI]，1.09 - 1.97；每1000人多2例），并且可能增加了GERD风险（RR，2.19；95% CI，1.48 - 3.25；每1000人多4例）。GLP-1RAs可能对其他胃肠道或胆道事件的风险几乎没有影响或没有影响。亚组分析表明，在纳入超重/肥胖或代谢功能障碍相关脂肪性肝炎/代谢功能障碍相关脂肪性肝病患者、具有减肥作用的GLP-1RAs或高剂量剂型的试验中，胆结石和GERD风险增加更为明显，尽管这些亚组效应无统计学意义。
GLP-1RAs与胆结石和GERD风险增加相关，但似乎不会增加其他胃肠道或胆道不良事件的风险。
