Ismaiel Abdulrahman, Scarlata Giuseppe Guido Maria, Boitos Irina, Leucuta Daniel-Corneliu, Popa Stefan-Lucian, Al Srouji Nahlah, Abenavoli Ludovico, Dumitrascu Dan L
2nd Department of Internal Medicine, "Iuliu Hatieganu" University of Medicine and Pharmacy, Cluj-Napoca, Romania.
Department of Health Sciences, University "Magna Graecia", Catanzaro, Italy.
Int J Obes (Lond). 2025 Aug 13. doi: 10.1038/s41366-025-01859-6.
Overweight and obesity are major global health issues, increasing disease risk and straining healthcare systems. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for weight loss but cause gastrointestinal side effects, affecting adherence. Research often focuses on diabetics, leaving a gap in understanding their effects on non-diabetic individuals with overweight or obesity. This systematic review and dose-response network meta-analysis addresses this gap, analyzing gastrointestinal adverse events from GLP-1 RAs in non-diabetic subjects with overweight or obesity.
We evaluated available evidence by searching PubMed and EMBASE databases, according to specific inclusion and exclusion eligibility criteria to evaluate gastrointestinal adverse events associated with GLP-1 RAs in non-diabetic individuals with overweight or obesity. Quality assessment of included studies was conducted using Cochrane Collaboration's tool.
Thirty-nine articles were included in the review showing a total number of 33,354 individuals. Nausea, vomiting, diarrhea, and constipation were the most common gastrointestinal adverse effects. All evaluated GLP-1 RAs led to a significant increase in nausea risk, with orforglipron showing the highest risk, followed by exenatide, tirzepatide, semaglutide, and liraglutide. Additionally, liraglutide, orforglipron, semaglutide, and tirzepatide were associated with increased vomiting risk, while cagrilinitide and exenatide showed no significant increase. Exenatide, cagrilinitide, orforglipron were not associated with diarrhea risk. Finally, semaglutide and liraglutide were associated to increased constipation risk, while cagrilinitide and exenatide showed no significant increase.
GLP-1 RAs showed several adverse gastrointestinal effects in non-diabetic patients with overweight or obesity. Understanding the different risk profiles of GLP-1 RAs helps clinicians make informed treatment decisions by balancing therapeutic benefits with potential side effects.
超重和肥胖是主要的全球健康问题，会增加疾病风险并给医疗系统带来压力。胰高血糖素样肽-1受体激动剂（GLP-1 RAs）对减肥有效，但会引起胃肠道副作用，影响药物依从性。研究通常集中在糖尿病患者身上，在了解其对超重或肥胖的非糖尿病个体的影响方面存在空白。本系统评价和剂量反应网络荟萃分析填补了这一空白，分析了超重或肥胖非糖尿病受试者使用GLP-1 RAs后的胃肠道不良事件。
我们通过检索PubMed和EMBASE数据库评估现有证据，根据特定的纳入和排除标准来评估超重或肥胖非糖尿病个体中与GLP-1 RAs相关的胃肠道不良事件。使用Cochrane协作网的工具对纳入研究进行质量评估。
该评价纳入了39篇文章，共涉及33354名个体。恶心、呕吐、腹泻和便秘是最常见的胃肠道不良反应。所有评估的GLP-1 RAs均导致恶心风险显著增加，奥佛利肽的风险最高，其次是艾塞那肽、替尔泊肽、司美格鲁肽和利拉鲁肽。此外，利拉鲁肽、奥佛利肽、司美格鲁肽和替尔泊肽与呕吐风险增加有关，而卡格列净肽和艾塞那肽未显示出显著增加。艾塞那肽、卡格列净肽、奥佛利肽与腹泻风险无关。最后，司美格鲁肽和利拉鲁肽与便秘风险增加有关，而卡格列净肽和艾塞那肽未显示出显著增加。
GLP-1 RAs在超重或肥胖的非糖尿病患者中显示出多种不良胃肠道效应。了解GLP-1 RAs的不同风险特征有助于临床医生在平衡治疗益处和潜在副作用的基础上做出明智的治疗决策。
