Department of Pharmacology, Alma Mater Studiorum-University of Bologna, Via Irnerio, 48, 40126, Bologna, BO, Italy.
Acta Diabetol. 2013 Aug;50(4):569-77. doi: 10.1007/s00592-011-0340-7. Epub 2011 Oct 19.
In patients with diabetes, disease per se, co-morbidities and drugs, including novel agents acting on the incretin system, have all been associated with pancreatitis with controversial data. We investigated the publicly available FDA Adverse Event Reporting System (FDA_AERS) database to gain insight into the possible association between antidiabetic agents and pancreatitis. To this aim, a case/non-case method was retrospectively performed on the FDA_AERS database (2004-2009 period). Cases were defined as reports of pancreatitis according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology. All other reports associated with antidiabetics were considered non-cases. The Reporting Odds Ratio (RORs), with corresponding 95% confidential interval (CI) and Mantel-Haenszel corrected P value, was calculated as a measure of disproportionality, with subsequent time-trend analysis. We retrieved 86,938 reports related to antidiabetics, corresponding to 159,226 drug-report combinations: 2,625 cases and 156,601 non-cases. Disproportionality was found only for exenatide (number of cases, 709; ROR, 1.76; 95% CI, 1.61-1.92; P MH < 0.001) and sitagliptin (128; 1.86; 1.54-2.24; <0.001). For exenatide, significant disproportionality appeared in the first quarter of 2008 (ROR, 1.24; 95% CI, 1.10-1.40; P MH < 0.001), soon after the FDA alert; for sitagliptin in the second quarter of 2008 (1.41; 1.05-1.90; 0.021). This temporal analysis found a striking influence of relevant FDA warnings on reporting of pancreatitis (the so-called notoriety bias) and is, therefore, recommended to avoid transforming a pharmacovigilance signal of alert automatically into an alarm. The precise quantification of the risk of pancreatitis associated with antidiabetics deserves assessment through specific disease-based registries.
在糖尿病患者中，疾病本身、合并症和药物（包括作用于肠促胰岛素系统的新型药物）都与胰腺炎有关，但相关数据存在争议。我们调查了公开的美国食品和药物管理局不良事件报告系统（FDA_AERS）数据库，以深入了解抗糖尿病药物与胰腺炎之间可能存在的关联。为此，我们对 FDA_AERS 数据库（2004-2009 年期间）进行了回顾性病例/非病例分析。根据监管活动医学词典（MedDRA）术语，病例定义为胰腺炎报告。所有与抗糖尿病药物相关的其他报告均被视为非病例。报告比值比（ROR）及其相应的 95%置信区间（CI）和修正 Mantel-Haenszel P 值被计算为一种衡量比例失调的指标，并随后进行时间趋势分析。我们检索了 86938 份与抗糖尿病药物相关的报告，涉及 159226 种药物报告组合：2625 例病例和 156601 例非病例。仅发现艾塞那肽（病例数 709 例；ROR 1.76；95%CI 1.61-1.92；P MH <0.001）和西他列汀（128 例；1.86；1.54-2.24；<0.001）存在比例失调。对于艾塞那肽，在 2008 年第一季度（ROR 1.24；95%CI 1.10-1.40；P MH <0.001）观察到显著的比例失调，这是在美国食品和药物管理局发出警报后不久；对于西他列汀，在 2008 年第二季度（1.41；1.05-1.90；0.021）观察到显著的比例失调。这种时间分析发现，相关的美国食品和药物管理局警告对胰腺炎报告具有显著影响（所谓的恶名偏见），因此建议避免将药物警戒信号的警报自动转化为警报。通过特定的基于疾病的登记处来评估与抗糖尿病药物相关的胰腺炎风险的精确量化是值得的。
