Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea.
Endocrinol Metab (Seoul). 2023 Aug;38(4):426-435. doi: 10.3803/EnM.2023.1737. Epub 2023 Jul 20.
The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors over the course of long-term treatment remain unclear, and concerns have been raised regarding the role of DPP-4 inhibitors in carcinogenesis in the pancreas. Earlier studies of pancreatic adverse events have reported conflicting results.
This study analyzed Korean National Health Insurance Service data from January 2009 to December 2012. Patients who had type 2 diabetes mellitus and took two or more oral glucose-lowering drugs (GLDs) were included. Patients prescribed DPP-4 inhibitors (n=51,482) or other GLDs (n=51,482) were matched at a 1:1 ratio using propensity score matching. The risk of pancreatic cancer was calculated using Kaplan-Meier curves and Cox proportional-hazards regression analysis.
During a median follow-up period of 7.95 years, 1,051 new cases of pancreatic cancer were identified. The adjusted hazard ratio (HR) for DPP-4 inhibitor use was 0.99 (95% confidence interval [CI], 0.88 to 1.12) compared with the other GLD group. In an analysis limited to cases diagnosed with pancreatic cancer during hospitalization, the adjusted HR for the use of DPP-4 inhibitors was 1.00 (95% CI, 0.86 to 1.17) compared with patients who took other GLDs. Using the other GLD group as the reference group, no trend was observed for elevated pancreatic cancer risk with increased DPP-4 inhibitor exposure.
In this population-based cohort study, DPP-4 inhibitor use over the course of relatively long-term follow-up showed no significant association with an elevated risk of pancreatic cancer.
长期治疗过程中二肽基肽酶 4（DPP-4）抑制剂的作用尚不清楚，并且人们对 DPP-4 抑制剂在胰腺发生癌变中的作用表示担忧。早期关于胰腺不良事件的研究报告结果相互矛盾。
本研究分析了 2009 年 1 月至 2012 年 12 月期间的韩国国家健康保险服务数据。纳入患有 2 型糖尿病且服用两种或更多种口服降糖药（GLD）的患者。按倾向评分匹配，将服用 DPP-4 抑制剂（n=51482）或其他 GLD（n=51482）的患者进行 1:1 匹配。使用 Kaplan-Meier 曲线和 Cox 比例风险回归分析计算胰腺癌的风险。
在中位随访 7.95 年期间，发现 1051 例新的胰腺癌病例。与其他 GLD 组相比，DPP-4 抑制剂使用的调整后危险比（HR）为 0.99（95%置信区间[CI]，0.88 至 1.12）。在仅分析因住院而诊断为胰腺癌的病例的分析中，与服用其他 GLD 的患者相比，使用 DPP-4 抑制剂的调整后 HR 为 1.00（95%CI，0.86 至 1.17）。与使用其他 GLD 组作为参考组相比，随着 DPP-4 抑制剂暴露量的增加，并未观察到胰腺癌风险升高的趋势。
在这项基于人群的队列研究中，在相对长期的随访过程中使用 DPP-4 抑制剂与胰腺癌风险升高没有显著关联。
