Cummings Tammy H, Magagnoli Joseph, Hardin James W, Sutton S Scott
Dorn Research Institute, Columbia Veterans Affairs Health Care System, Columbia, SC 29209, USA.
Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, SC 29208, USA.
Pathogens. 2022 Feb 19;11(2):270. doi: 10.3390/pathogens11020270.
Obesity is a risk factor for the development of influenza by leading to a chronic inflammatory state and T-cell dysfunction. Based upon preclinical research, metformin has influenza activity by restoring T-cell function and improving the immune response.
We aimed to evaluate the potential drug repurposing of metformin for the management of influenza among patients with obesity utilizing national claims data in an electronic health record database.
The VA Informatics and Computing Infrastructure (VINCI) was utilized to obtain individual-level information on demographics, administrative claims, and pharmacy dispensation. A cohort was created among individuals with laboratory confirmed diagnosis of influenza with a diagnosis of fever, cough, influenza, or acute upper respiratory infection in an outpatient setting. The study outcome was death after diagnosis of influenza. Cohorts were formed using diabetes status and metformin exposure prior to a positive influenza diagnosis. Hazard ratios for mortality were estimated using a cox proportional hazards model adjusting for baseline covariates and a sub-analysis was conducted utilizing propensity score matching. A greedy nearest neighbor algorithm was utilized to match 1 to 1 non-metformin diabetic controls and non-diabetic controls to diabetic patients receiving metformin.
A total of 3551 patients met the inclusion criteria and were evaluated in our study. The cohorts consisted of 1461 patients in the non-diabetic cohort, 1597 patients in the diabetic / metformin cohort, and 493 patients in the diabetic no metformin cohort. Compared to non-diabetic patients, diabetic patients with metformin had a lower rate of death (aHR 0.78, 95% CI 0.609-0.999). There was not a statistical difference between the non-diabetic patients and the diabetic patients without metformin (aHR 1.046, 95% CI 0.781-1.400). The propensity score matched cohorts revealed consistent results with the primary analysis.
Our results demonstrated patients with obesity and a history of metformin treatment have lower influenza mortality.
肥胖通过导致慢性炎症状态和T细胞功能障碍，成为流感发病的一个风险因素。基于临床前研究，二甲双胍可通过恢复T细胞功能和改善免疫反应而具有抗流感活性。
我们旨在利用电子健康记录数据库中的国家索赔数据，评估二甲双胍在肥胖患者中治疗流感的潜在药物再利用情况。
利用退伍军人事务部信息学和计算基础设施（VINCI）获取有关人口统计学、行政索赔和药房配药的个人层面信息。在门诊环境中，在实验室确诊为流感且诊断为发热、咳嗽、流感或急性上呼吸道感染的个体中创建一个队列。研究结局为流感诊断后的死亡情况。根据糖尿病状态和流感诊断阳性之前的二甲双胍暴露情况形成队列。使用Cox比例风险模型估计死亡率的风险比，并对基线协变量进行调整，同时利用倾向得分匹配进行亚分析。采用贪婪最近邻算法将1名非二甲双胍糖尿病对照和非糖尿病对照与接受二甲双胍治疗的糖尿病患者进行1:1匹配。
共有3551例患者符合纳入标准并在我们的研究中接受评估。队列包括非糖尿病队列中的1461例患者、糖尿病/二甲双胍队列中的1597例患者以及糖尿病未使用二甲双胍队列中的493例患者。与非糖尿病患者相比，使用二甲双胍的糖尿病患者死亡率较低（校正风险比0.78，95%可信区间0.609 - 0.999）。未使用二甲双胍的糖尿病患者与非糖尿病患者之间无统计学差异（校正风险比1.046，95%可信区间0.781 - 1.400）。倾向得分匹配队列的结果与初步分析一致。
我们的结果表明，有肥胖病史且接受过二甲双胍治疗的患者流感死亡率较低。
