Optum Epidemiology, Boston, Massachusetts.
Global Safety, Novo Nordisk A/S, Copenhagen, Denmark.
Diabetes Obes Metab. 2019 Aug;21(8):1837-1848. doi: 10.1111/dom.13739. Epub 2019 May 24.
Both acute pancreatitis (AP) and pancreatic cancer (PC) have been areas of focus for studies of incretin drugs. This 5-year prospective cohort study aimed to quantify possible associations between liraglutide and risk of AP and PC as compared to other antidiabetic drugs (ADs).
Patients initiating liraglutide or other ADs who were enrolled in a US health plan (2010-2014) were included. Comparisons of AP and PC incidence rates were made between matched cohorts of liraglutide initiators and initiators of other ADs. Adjudicated AP cases and algorithm-based PC cases were identified. Propensity score-matched intention-to-treat (ITT) and time-on-drug (TOD) analyses were completed using Poisson regression. A latency analysis was performed for PC.
Median follow-up was 405 days for AP cohorts (9995 liraglutide, 1:1 matched to all comparators) and 503 days for PC cohorts (35 163 liraglutide, 1:1 matched to all comparators). In the primary AP analysis, "current" use of liraglutide was not significantly associated with elevated risk across comparators (all comparators relative risk [RR] = 1.2; 95% confidence interval [CI], 0.6-2.3). ITT results were similar where, in the primary analysis, no RRs were significantly associated with PC (all comparators RR = 0.7; 95% CI, 0.3-1.4); latency and TOD analyses did not alter findings. There was no evidence of a dose-response effect.
Liraglutide was not associated with an increased risk of AP or PC, although risk estimates were more variable for AP, and numbers of cases for both outcomes were limited because of the rarity of outcomes.
急性胰腺炎(AP)和胰腺癌(PC)一直是肠降血糖素类药物研究的重点。本 5 年前瞻性队列研究旨在定量比较利拉鲁肽与其他抗糖尿病药物(AD)相比,AP 和 PC 风险的可能关联。
纳入 2010-2014 年在美国健康计划中开始使用利拉鲁肽或其他 AD 的患者。在利拉鲁肽和其他 AD 起始者的匹配队列之间比较 AP 和 PC 的发病率。通过裁定的 AP 病例和基于算法的 PC 病例进行识别。使用泊松回归完成倾向评分匹配的意向治疗(ITT)和药物使用时间(TOD)分析。进行了 PC 的潜伏期分析。
AP 队列的中位随访时间为 405 天(9995 例利拉鲁肽,与所有对照物 1:1 匹配),PC 队列为 503 天(35163 例利拉鲁肽,与所有对照物 1:1 匹配)。在主要的 AP 分析中,与所有对照物相比,“当前”使用利拉鲁肽与风险升高无关(所有对照物相对风险 [RR] = 1.2;95%置信区间 [CI],0.6-2.3)。在主要分析中,ITT 结果也相似,没有 RR 与 PC 显著相关(所有对照物 RR = 0.7;95%CI,0.3-1.4);潜伏期和 TOD 分析并未改变结果。没有证据表明存在剂量反应关系。
利拉鲁肽与 AP 或 PC 的风险增加无关,尽管 AP 的风险估计更为多变,并且由于结局罕见,两种结局的病例数都有限。