Some epidemiological data have suggested an elevated risk of acute pancreatitis and pancreatic cancer after exposure to glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase (DPP)-4 inhibitors. Recently, such outcomes have been assessed and adjudicated as adverse events of special interest in cardiovascular outcomes studies. We performed a meta-analysis of cases of acute pancreatitis and pancreatic cancer as well as any malignant neoplasm reported in cardiovascular outcomes trials (CVOTs) with GLP-1 receptor agonists and DPP-4 inhibitors. The numbers of cases observed with active drug or placebo (both on a background of standard care) were related to patient-years of observation. Rate ratios and their confidence intervals were calculated for the individual agents as well as for the classes of GLP-1 receptor agonists and DPP-4 inhibitors. Neither data on individual CVOTs of GLP-1 receptor agonists nor their meta-analysis [rate ratio: 1.05 (0.78-1.41)] indicated a significantly elevated risk of acute pancreatitis. All individual DPP-4 inhibitors displayed a non-significant trend towards an increased risk of acute pancreatitis, which was significant in the meta-analysis [1.75 (1.14-2.70); P = 0.01]. Neither GLP-1 receptor agonists nor DPP-4 inhibitors were associated with a significantly elevated or reduced risk of pancreatic cancer or for the totality of all malignant neoplasms. Based on a large database of randomized, placebo-controlled, prospective cardiovascular outcomes studies with GLP-1 receptor agonists and DPP-4 inhibitors, no signal for pancreatic cancer or any malignant neoplasms were detected. However, a 75% risk increase for the development of an acute pancreatitis was seen in the meta-analysis of DPP-4 inhibitor CVOTs.

中文翻译：

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基于肠抑素的降糖药物和急性胰腺炎和恶性肿瘤的风险：基于心血管预后试验的荟萃分析。

一些流行病学数据表明，暴露于胰高血糖素样肽（GLP）-1受体激动剂和二肽基肽酶（DPP）-4抑制剂后，发生急性胰腺炎和胰腺癌的风险升高。最近，在心血管结局研究中，已将此类结局评估并裁定为特别令人关注的不良事件。我们对急性胰腺炎和胰腺癌以及GLP-1受体激动剂和DPP-4抑制剂在心血管结果试验（CVOT）中报告的任何恶性肿瘤病例进行了荟萃分析。使用活性药物或安慰剂观察到的病例数（均以标准护理为背景）与患者的观察年数相关。计算单个药剂以及GLP-1受体激动剂和DPP-4抑制剂类别的速率比及其置信区间。关于GLP-1受体激动剂的单个CVOT的数据或它们的荟萃分析[比率[1.05（0.78-1.41）]]均未显示急性胰腺炎的风险显着升高。所有单独的DPP-4抑制剂均显示出急性胰腺炎风险增加的非显着趋势，这在荟萃分析中很显着[1.75（1.14-2.70）；P = 0.01]。GLP-1受体激动剂和DPP-4抑制剂均未与胰腺癌或所有恶性肿瘤总数的显着升高或降低相关。基于大型的随机，安慰剂对照的数据库，使用GLP-1受体激动剂和DPP-4抑制剂进行的前瞻性心血管预后研究，未检测到胰腺癌或任何恶性肿瘤的信号。然而，在对DPP-4抑制剂CVOT的荟萃分析中发现，急性胰腺炎发生的风险增加了75％。