Glucagon-Like Peptide-1 Receptor Agonists and Gastrointestinal Adverse Events: A Systematic Review and Meta-Analysis.

However, there are concerns regarding their association with serious gastrointestinal adverse events, although findings have been inconsistent.

然而，人们担心它们与严重的胃肠道不良事件有关，尽管研究结果并不一致。

Methods

We systematically searched 5 databases for placebo-controlledrandomized 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.

我们系统地检索了5个数据库，以评估在2型糖尿病、超重/肥胖或代谢功能障碍相关性脂肪性肝炎/代谢功能障碍相关性脂肪性肝病患者中使用GLP-1RAs的安慰剂对照随机对照试验。

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.

我们纳入了报告胆囊炎、胆石症、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。

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.

使用随机效应模型进行了荟萃分析，通过亚组分析评估了基于患者人群、GLP-1RA与双重激动剂配方、减重特性、剂量和作用持续时间的风险。

Results

We included 55 randomized controlled trials involving 106,395 participants.

我们纳入了55项涉及106,395名参与者的随机对照试验。

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.

与安慰剂相比，GLP-1RAs增加了胆石症的风险（风险比[RR]，1.46；95%置信区间，1.09-1.97；每1000人中多2例）并且可能增加了胃食管反流病（GERD）的风险（RR，2.19；95%置信区间，1.48-3.25；每1000人中多4例）。

GLP-1RAs probably have little or no effect on the risk of other gastrointestinal or biliary events.

GLP-1RAs可能对其他胃肠道或胆道事件的风险影响不大或没有影响。

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.

亚组分析显示，在包括超重/肥胖个体或与代谢功能障碍相关的脂肪性肝炎/代谢功能障碍相关的脂肪性肝病、减重诱导的GLP-1RAs或高剂量制剂的试验中，胆石症和胃食管反流病的风险增加更为显著，尽管这些亚组效应在统计上并不显著。

Conclusions

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.

GLP-1RAs与胆石症和胃食管反流病的风险增加有关，但似乎并不增加其他胃肠道或胆道不良事件的风险。