St. Louis Veterans Health Administration Medical Center, St. Louis, Missouri.
Division of Public Health Sciences, Department of Surgery, and Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri.
Cancer Epidemiol Biomarkers Prev. 2020 Jan;29(1):169-175. doi: 10.1158/1055-9965.EPI-19-0781. Epub 2019 Nov 4.
The effect of metformin use on survival among patients with pancreatic ductal adenocarcinoma (PDAC) is controversial. Furthermore, there are no data on African American patients. To address these, we analyzed data from the United States Veterans Health Administration (VHA).
A population-based retrospective cohort study evaluating overall survival among 3,811 patients with PDAC with preexisting diabetes mellitus, diagnosed with PDAC within the VHA between 1998 and 2013. We calculated HRs and 95% confidence intervals (CI) using multivariable adjusted time-varying Cox proportional hazards regression to control for immortal time bias and confounders.
Metformin use was not associated with overall survival in the complete analyses (HR = 1.05; 95% CI, 0.92-1.14; = 0.28). However, among patients who were metformin naïve at the time of PDAC diagnosis ( = 1,158), metformin use was associated with improved overall survival in non-Hispanic white patients (HR = 0.78; 95% CI, 0.61-0.99; = 0.04), but not African American patients (HR = 1.20; 95% CI, 0.75-1.93; = 0.45). The survival benefit among non-Hispanic whites was limited to patients with metastatic disease (HR = 0.67; 95% CI, 0.44-1.01; = 0.06). Among African American patients with metastatic disease, HR was 1.30 (95% CI, 0.77-2.53; = 0.28). There was a suggestion of heterogeneity by race in patients with metastatic disease ( = 0.05).
We observed no associations between metformin use and survival in patients with PDAC, but there appears to be a survival benefit among non-Hispanic white patients who were metformin naïve at the time of PDAC diagnosis.
If confirmed in other studies, our findings suggest that metformin as an adjunctive treatment for PDAC may not improve survival among African American patients.
二甲双胍在胰腺导管腺癌(PDAC)患者中的生存影响存在争议。此外,尚无关于非裔美国患者的相关数据。为了解决这些问题,我们分析了美国退伍军人健康管理局(VHA)的数据。
这是一项基于人群的回顾性队列研究,评估了 3811 名患有 PDAC 且患有糖尿病的患者的总生存率,这些患者在 1998 年至 2013 年期间在 VHA 中被诊断为 PDAC。我们使用多变量调整的时间变化 Cox 比例风险回归来计算 HR 和 95%置信区间(CI),以控制不朽时间偏倚和混杂因素。
二甲双胍的使用与整体生存情况在完整分析中没有关联(HR=1.05;95%CI,0.92-1.14;P=0.28)。然而,在 PDAC 诊断时为二甲双胍初治患者中(n=1158),二甲双胍的使用与非西班牙裔白人患者的总生存率提高相关(HR=0.78;95%CI,0.61-0.99;P=0.04),但与非裔美国患者无关(HR=1.20;95%CI,0.75-1.93;P=0.45)。非西班牙裔白人患者的生存获益仅限于转移性疾病患者(HR=0.67;95%CI,0.44-1.01;P=0.06)。对于患有转移性疾病的非裔美国患者,HR 为 1.30(95%CI,0.77-2.53;P=0.28)。在患有转移性疾病的患者中,种族之间存在异质性的迹象(P=0.05)。
我们在 PDAC 患者中未观察到二甲双胍使用与生存之间的关联,但在 PDAC 诊断时为二甲双胍初治的非西班牙裔白人患者中似乎存在生存获益。
如果在其他研究中得到证实,我们的研究结果表明,二甲双胍作为 PDAC 的辅助治疗可能不会提高非裔美国患者的生存率。