Division of Diabetology, Medical Department I, St. Josef-Hospital (Ruhr-Universität Bochum), Bochum, Germany.
Division of Gastroenterology, University Hospital of Geneva, Geneva, Switzerland.
Diabetes Care. 2017 May;40(5):647-654. doi: 10.2337/dc16-0984. Epub 2017 Mar 10.
To assess the risk of acute pancreatitis during treatment with glucagon-like peptide 1 receptor agonist dulaglutide, placebo, and active comparators across phase 2/3 dulaglutide trials.
A total of 6,005 patients with type 2 diabetes participated (dulaglutide group = 4,006 [dose range 0.1-3.0 mg]; active comparator group [metformin, sitagliptin, exenatide twice daily, insulin glargine] = 1,541; placebo group = 703; 245 placebo-treated patients subsequently received dulaglutide or sitagliptin and were also included in these groups) for up to 104 weeks. The following events were adjudicated: investigator-reported pancreatitis, adverse events (AEs) of severe or serious abdominal pain of unknown etiology, and confirmed asymptomatic increases in pancreatic enzymes ≥3× the upper limit of normal range.
Overall, 203 events from 151 patients underwent adjudication (dulaglutide group = 108; comparator group including placebo = 43). Acute pancreatitis was confirmed by adjudication in seven patients (dulaglutide = 3, placebo = 1, sitagliptin = 3). Exposure-adjusted incidence rates were as follows: dulaglutide group 0.85 patients/1,000 patient-years, placebo group 3.52 patients/1,000 patient-years, sitagliptin group 4.71 patients/1,000 patient-years. No events of pancreatitis were confirmed by adjudication in patients treated with exenatide twice daily, metformin, or glargine. Increases in median values of lipase and pancreatic amylase within the normal range were observed with all treatments except glargine. These changes were not associated with AEs.
The exposure-adjusted incidence rate of acute pancreatitis in dulaglutide-treated patients was similar to the rates with placebo, with few reported cases during the entire program.
评估在 2/3 期度拉糖肽试验中，接受胰高血糖素样肽 1 受体激动剂度拉糖肽、安慰剂和活性对照药物治疗的患者发生急性胰腺炎的风险。
共有 6005 例 2 型糖尿病患者参与（度拉糖肽组 = 4006 [剂量范围 0.1-3.0mg]；活性对照药物组 [二甲双胍、西格列汀、每日两次艾塞那肽、甘精胰岛素] = 1541；安慰剂组 = 703；703 名安慰剂治疗的患者随后接受了度拉糖肽或西格列汀治疗，也被纳入这些组），治疗时间最长达 104 周。以下事件经裁决后判定：研究者报告的胰腺炎、原因不明的严重或严重腹痛的不良事件（AE）和确证的无症状性胰腺酶升高≥正常上限的 3 倍。
总体而言，151 名患者中有 203 例事件进行了裁决（度拉糖肽组 = 108；包括安慰剂的对照药物组 = 43）。7 名患者的胰腺炎经裁决后确证（度拉糖肽组 3 例，安慰剂组 1 例，西格列汀组 3 例）。度拉糖肽组的调整暴露发生率为 0.85 例/1000 患者年，安慰剂组为 3.52 例/1000 患者年，西格列汀组为 4.71 例/1000 患者年。接受每日两次艾塞那肽、二甲双胍或甘精胰岛素治疗的患者中，未确证有胰腺炎事件。除甘精胰岛素外，所有治疗组的脂肪酶和胰淀粉酶中位值均在正常范围内升高。这些变化与 AE 无关。
在度拉糖肽治疗的患者中，急性胰腺炎的调整暴露发生率与安慰剂相似，在整个研究期间报告的病例很少。
