Vetter Marion L, Johnsson Kristina, Hardy Elise, Wang Hui, Iqbal Nayyar
Bristol-Myers Squibb, Lawrenceville, NJ, USA.
Janssen Pharmaceutical Companies of Johnson & Johnson, Philadelphia, PA, USA.
Diabetes Ther. 2019 Aug;10(4):1249-1270. doi: 10.1007/s13300-019-0627-1. Epub 2019 May 10.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for treatment of type 2 diabetes mellitus; however, there have been concerns that GLP-1RA treatment may be associated with an increased incidence of pancreatitis. This study aimed to evaluate the incidence of pancreatitis in a pooled population of type 2 diabetes trials from the clinical development program of the GLP-1RA exenatide as well as to describe patient-level data for all reported cases.
The primary analysis examined pooled data among patients with type 2 diabetes from the controlled arms of 35 trials (ranging from 4 to 234 weeks' duration) in the integrated clinical databases for exenatide twice daily, once weekly, and once-weekly suspension, excluding comparator arms with other incretin-based therapies. The exposure-adjusted incidence rate (EAIR) of pancreatitis was calculated for exenatide and non-exenatide (non-incretin-based therapy or placebo) treatment groups. Patient-level data were described for all pancreatitis incidences.
The primary analysis included 5596 patients who received exenatide and 4462 in the non-exenatide group. The mean duration of study medication exposure for the exenatide and non-exenatide treatment groups was 57.0 and 47.9 weeks, respectively. Pancreatitis was diagnosed in 14 patients (exenatide, n = 8; non-exenatide, n = 6), of whom 13 recovered with or without sequelae. The pancreatitis EAIR was 0.1195 events per 100 patient-years [95% confidence interval (CI), 0.0516-0.2154] in the exenatide group versus 0.1276 events per 100 patient-years (95% CI 0.0468-0.2482) in the non-exenatide treatment group. The EAIR ratio for the exenatide versus non-exenatide treatment group was 0.761 (95% CI 0.231-2.510).
In this pooled analysis of 10,058 patients among studies comparing exenatide with other glucose-lowering medications or placebo, pancreatitis was rare. The EAIRs of pancreatitis were low and similar between exenatide and non-exenatide treatment groups. No evidence of an association between exenatide and pancreatitis was observed.
Bristol-Myers Squibb and AstraZeneca. Plain language summary available for this article.
胰高血糖素样肽-1受体激动剂（GLP-1RAs）被广泛用于治疗2型糖尿病；然而，有人担心GLP-1RA治疗可能与胰腺炎发病率增加有关。本研究旨在评估来自GLP-1RA艾塞那肽临床开发项目的2型糖尿病试验汇总人群中胰腺炎的发病率，并描述所有报告病例的患者层面数据。
主要分析检查了来自35项试验（持续时间为4至234周）对照臂中2型糖尿病患者的汇总数据，这些试验在艾塞那肽每日两次、每周一次和每周一次悬液的综合临床数据库中进行，不包括使用其他基于肠促胰岛素疗法的对照臂。计算了艾塞那肽和非艾塞那肽（非基于肠促胰岛素的疗法或安慰剂）治疗组胰腺炎的暴露调整发病率（EAIR）。描述了所有胰腺炎发病的患者层面数据。
主要分析纳入了5596例接受艾塞那肽治疗的患者和4462例非艾塞那肽组患者。艾塞那肽和非艾塞那肽治疗组的研究药物平均暴露持续时间分别为57.0周和47.9周。14例患者被诊断为胰腺炎（艾塞那肽组，n = 8；非艾塞那肽组，n = 6），其中13例康复，有或无后遗症。艾塞那肽组胰腺炎的EAIR为每100患者年0.1195例事件[95%置信区间（CI），0.0516 - 0.2154]，而非艾塞那肽治疗组为每100患者年0.1276例事件（95% CI 0.0468 - 0.2482）。艾塞那肽组与非艾塞那肽治疗组的EAIR比值为0.761（95% CI 0.231 - 2.510）。
在这项对10,058例患者进行的将艾塞那肽与其他降糖药物或安慰剂进行比较的研究汇总分析中，胰腺炎很罕见。艾塞那肽和非艾塞那肽治疗组的胰腺炎EAIR较低且相似。未观察到艾塞那肽与胰腺炎之间存在关联的证据。
百时美施贵宝公司和阿斯利康公司。本文提供通俗易懂的摘要。
