Kalathiya Urja N, Herrin Jeph, Swarna Kavya Sindu, Deng Yihong, Polley Eric C, Neumiller Joshua J, Galindo Rodolfo J, Umpierrez Guillermo E, Ross Joseph S, Mickelson Mindy M, McCoy Rozalina G
University of Maryland School of Medicine, Baltimore, MD.
Section of Cardiovascular Medicine, Department of Medicine, Yale School of Medicine, New Haven, CT.
Endocr Pract. 2025 Sep 11. doi: 10.1016/j.eprac.2025.09.004.
Evidence on acute pancreatitis and pancreatic cancer with glucagon-like peptide-1 receptor agonist [GLP-1RA] and dipeptidyl peptidase-4 inhibitor [DPP-4i] therapy is mixed and no studies examined this risk directly across all commonly used classes of type 2 diabetes (T2D) medications, particularly sodium-glucose cotransporter 2 inhibitors (SGLT2i) and sulfonylureas.
De-identified claims data from OptumLabs Data Warehouse and fee-for-service Medicare were used to emulate a target trial examining the risks of incident acute pancreatitis and pancreatic cancer among adults with T2D and moderate cardiovascular risk. Propensity scores (estimated using the SuperLearner ensemble method) and inverse probability of treatment weighting emulated random treatment assignment to GLP-1RA, DPP-4i, SGLT2i, or sulfonylurea.
The weighted study cohort included 388,262 patients starting GLP-1RA (N=44,084), DPP-4i (N=82,079), SGLT2i (N=56,463), or a sulfonylurea (N=205,636). SGLT2i was associated with lower risk of acute pancreatitis compared to DPP-4i (HR 0.82; 95% CI 0.68-0.98). Conversely, sulfonylurea was associated with higher risk compared to GLP-1RA (HR 1.28; 95% CI 1.03-1.56) and SGLT2i (HR 1.32; 95% CI 1.12-1.57). There was no difference in acute pancreatitis risk between GLP-1RA and DPP-4i or GLP-1RA and SGLT2i. The risk of pancreatic cancer was lower with GLP-1RA compared to DPP-4i (HR 0.56; 95% CI 0.40-0.77). In contrast, risk was higher with SGLT2i and sulfonylurea compared to GLP-1RA (HR 1.67; 95% CI 1.12-2.49 and HR 1.60; 95% CI 1.17-2.19, respectively).
GLP-1RA and DPP-4i therapy was not associated with increased risk of adverse pancreatic events. The lower risk of acute pancreatitis with SGLT2i therapy warrants further exploration.
关于胰高血糖素样肽-1受体激动剂[GLP-1RA]和二肽基肽酶-4抑制剂[DPP-4i]治疗急性胰腺炎和胰腺癌的证据不一，且尚无研究直接考察所有常用的2型糖尿病（T2D）药物类别中的这种风险，尤其是钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）和磺脲类药物。
使用来自OptumLabs数据仓库和按服务收费的医疗保险的去识别化索赔数据，模拟一项目标试验，以考察T2D且有中度心血管风险的成年人发生急性胰腺炎和胰腺癌的风险。倾向评分（使用SuperLearner集成方法估算）和治疗权重的逆概率模拟随机分配接受GLP-1RA、DPP-4i、SGLT2i或磺脲类药物治疗。
加权研究队列包括388,262例开始使用GLP-1RA（N = 44,084）、DPP-4i（N = 82,079）、SGLT2i（N = 56,463）或磺脲类药物（N = 205,636）的患者。与DPP-4i相比，SGLT2i与较低的急性胰腺炎风险相关（风险比[HR] 0.82；95%置信区间[CI] 0.68 - 0.98）。相反，与GLP-1RA相比（HR 1.28；95% CI 1.03 - 1.56）以及与SGLT2i相比（HR 1.32；95% CI 1.12 - 1.57），磺脲类药物与较高风险相关。GLP-1RA与DPP-4i之间或GLP-1RA与SGLT2i之间的急性胰腺炎风险无差异。与DPP-4i相比，GLP-1RA的胰腺癌风险较低（HR 0.56；95% CI 0.40 - 0.77）。相比之下，与GLP-1RA相比，SGLT2i和磺脲类药物的风险较高（分别为HR 1.67；95% CI 1.12 - 2.49和HR 1.60；95% CI 1.17 - 2.
