Cao Chuqing, Yang Shuting, Zhou Zhiguang
Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
Key Laboratory of Diabetes Immunology, Central South University, Ministry of Education, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China.
Endocrine. 2020 Jun;68(3):518-525. doi: 10.1007/s12020-020-02223-6. Epub 2020 Feb 26.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been suggested to be associated with an increased risk of pancreatitis and pancreatic cancer. The aim of this meta-analysis was to collect data from large-scale cardiovascular outcome trials (CVOTs) to assess the effect of GLP-1RAs on the incidence of acute pancreatitis and pancreatic cancer.
Database of Medline, Embase, and the Cochrane Central Register of Controlled Trials were extensively searched up to October 10, 2019. Randomized controlled trials were eligible if they compared GLP-RA with placebo as add-on therapy to standard care in T2DM patients, and reported outcomes required for cardiovascular safety studies and events of acute pancreatitis and/or pancreatic cancer. Peto odds ratio (OR) with 95% confidence interval (CI) was calculated for acute pancreatitis and pancreatic cancer.
Seven CVOTs enrolling 56,004 patients with T2DM were identified, with a median follow-up time ranging from 1.3 to 5.4 years. A total of 180 cases of acute pancreatitis and 108 cases of pancreatic cancer were reported. The risk of either acute pancreatitis or pancreatic cancer with GLP-1-RA treatment was not significantly different from that observed in placebo arm (Peto OR [95% CI] 1.05 [0.78-1.40], P = 0.76, and 1.12 [0.77-1.63], P = 0.56, respectively), and the results remained robust to sensitivity analyses.
Pooled analysis of CVOTs did not suggest any increased risk of either acute pancreatitis or pancreatic cancer with GLP-1RA treatment in T2DM patients.
胰高血糖素样肽-1受体激动剂（GLP-1RAs）被认为与胰腺炎和胰腺癌风险增加有关。本荟萃分析的目的是收集大规模心血管结局试验（CVOTs）的数据，以评估GLP-1RAs对急性胰腺炎和胰腺癌发病率的影响。
对截至2019年10月10日的Medline、Embase和Cochrane对照试验中央注册库数据库进行了广泛检索。随机对照试验符合纳入标准，需满足将GLP-RA与安慰剂作为2型糖尿病患者标准治疗的附加疗法进行比较，并报告心血管安全性研究所需的结局以及急性胰腺炎和/或胰腺癌事件。计算急性胰腺炎和胰腺癌的Peto比值比（OR）及95%置信区间（CI）。
确定了7项纳入56004例2型糖尿病患者的CVOTs，中位随访时间为1.3至5.4年。共报告了180例急性胰腺炎和108例胰腺癌。接受GLP-1-RA治疗的患者发生急性胰腺炎或胰腺癌的风险与安慰剂组观察到的风险无显著差异（Peto OR [95% CI]分别为1.05 [0.78 - 1.40]，P = 0.76，以及1.12 [0.77 - 1.63]，P = 0.56），敏感性分析结果依然稳健。
CVOTs的汇总分析未提示2型糖尿病患者接受GLP-1RA治疗会增加急性胰腺炎或胰腺癌的风险。
