Section of Geriatric Cardiology and Medicine, Department of Cardiovascular Medicine, Careggi Teaching Hospital, Florence, Italy.
Curr Med Res Opin. 2011 Nov;27 Suppl 3:57-64. doi: 10.1185/03007995.2011.602964.
Dipeptidyl peptidase-4 inhibitors (DPP4i) have been recently associated with increased risk of pancreatitis and cancer. The aim of the present meta-analysis of randomized clinical trials is the assessment of the effect of DPP4i on the incidence of major cardiovascular events (MACE), cancer, and pancreatitis.
An extensive Medline and Embase search for 'vildagliptin', 'sitagliptin', 'saxagliptin', 'alogliptin', 'linagliptin', and 'dutogliptin' was performed, collecting all randomized clinical trials on humans up to March 1, 2011. The present meta-analysis was therefore performed including all randomized clinical trials with a duration of at least 24 weeks, enrolling patients with type 2 diabetes, comparing DPP4i with either placebo or active drugs. Completed but still unpublished trials were identified through a search of www.clinicaltrials.gov, Food and Drug Administration, and European Medicines Agency website.
Fifty-three trials enrolling 20,312 and 13,569 patients for DPP4i and comparators, respectively, were included, reporting 176 malignancies, 257 MACE, and 22 pancreatitis. DPP4i, compared with placebo or other treatment, were associated with a similar risk of cancer (MH-OR 1.020 [0.742-1.402]; p = 0.90) and pancreatitis (0.786 [0.357-1.734], p = 0.55), and with a reduced risk of MACE (MH-OR 0.689 [0.528-0.899], p = 0.006).
The present meta-analysis seems to exclude any relevant short term effect of DPP4i on the incidence of cancer and suggest a possible protection from cardiovascular events. This result should be interpreted with caution, as those events were not the principal endpoint, the trial duration was short, and the characteristics of patients included could be different from routine clinical practice.
二肽基肽酶-4 抑制剂（DPP4i）最近与胰腺炎和癌症风险增加有关。本随机临床试验荟萃分析的目的是评估 DPP4i 对主要心血管事件（MACE）、癌症和胰腺炎发生率的影响。
对 Medline 和 Embase 进行了广泛的“vildagliptin”、“sitagliptin”、“saxagliptin”、“alogliptin”、“linagliptin”和“dutogliptin”搜索，收集截至 2011 年 3 月 1 日的所有关于人类的随机临床试验。因此，本荟萃分析包括所有持续时间至少 24 周的随机临床试验，纳入 2 型糖尿病患者，比较 DPP4i 与安慰剂或活性药物的疗效。通过搜索 www.clinicaltrials.gov、美国食品和药物管理局以及欧洲药品管理局网站，确定了已完成但尚未公布的试验。
共纳入 53 项试验，分别纳入 20312 例和 13569 例患者接受 DPP4i 和对照药物治疗，报告了 176 例恶性肿瘤、257 例 MACE 和 22 例胰腺炎。与安慰剂或其他治疗相比，DPP4i 与癌症（MH-OR 1.020 [0.742-1.402]；p = 0.90）和胰腺炎（0.786 [0.357-1.734]，p = 0.55）的风险相似，与 MACE 的风险降低相关（MH-OR 0.689 [0.528-0.899]，p = 0.006）。
本荟萃分析似乎排除了 DPP4i 对癌症发生率的任何短期相关影响，并提示其可能对心血管事件具有保护作用。该结果应谨慎解释，因为这些事件不是主要终点，试验持续时间较短，纳入的患者特征可能与常规临床实践不同。
