Division of General Internal Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Lancet Healthy Longev. 2021 Jan;2(1):e34-e41. doi: 10.1016/S2666-7568(20)30033-7. Epub 2020 Dec 3.
Type 2 diabetes and obesity, as states of chronic inflammation, are risk factors for severe COVID-19. Metformin has cytokine-reducing and sex-specific immunomodulatory effects. Our aim was to identify whether metformin reduced COVID-19-related mortality and whether sex-specific interactions exist.
In this retrospective cohort analysis, we assessed de-identified claims data from UnitedHealth Group (UHG)'s Clinical Discovery Claims Database. Patient data were eligible for inclusion if they were aged 18 years or older; had type 2 diabetes or obesity (defined based on claims); at least 6 months of continuous enrolment in 2019; and admission to hospital for COVID-19 confirmed by PCR, manual chart review by UHG, or reported from the hospital to UHG. The primary outcome was in-hospital mortality from COVID-19. The independent variable of interest was home metformin use, defined as more than 90 days of claims during the year before admission to hospital. Covariates were comorbidities, medications, demographics, and state. Heterogeneity of effect was assessed by sex. For the Cox proportional hazards, censoring was done on the basis of claims made after admission to hospital up to June 7, 2020, with a best outcome approach. Propensity-matched mixed-effects logistic regression was done, stratified by metformin use.
6256 of the 15 380 individuals with pharmacy claims data from Jan 1 to June 7, 2020 were eligible for inclusion. 3302 (52·8%) of 6256 were women. Metformin use was not associated with significantly decreased mortality in the overall sample of men and women by either Cox proportional hazards stratified model (hazard ratio [HR] 0·887 [95% CI 0·782-1·008]) or propensity matching (odds ratio [OR] 0·912 [95% CI 0·777-1·071], p=0·15). Metformin was associated with decreased mortality in women by Cox proportional hazards (HR 0·785, 95% CI 0·650-0·951) and propensity matching (OR 0·759, 95% CI 0·601-0·960, p=0·021). There was no significant reduction in mortality among men (HR 0·957, 95% CI 0·82-1·14; p=0·689 by Cox proportional hazards).
Metformin was significantly associated with reduced mortality in women with obesity or type 2 diabetes who were admitted to hospital for COVID-19. Prospective studies are needed to understand mechanism and causality. If findings are reproducible, metformin could be widely distributed for prevention of COVID-19 mortality, because it is safe and inexpensive.
National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; Patient-Centered Outcomes Research Institute; Minnesota Learning Health System Mentored Training Program, M Health Fairview Institutional Funds; National Center for Advancing Translational Sciences; and National Cancer Institute.
2 型糖尿病和肥胖症作为慢性炎症状态，是 COVID-19 严重程度的危险因素。二甲双胍具有降低细胞因子和具有性别特异性的免疫调节作用。我们的目的是确定二甲双胍是否降低了 COVID-19 相关死亡率，以及是否存在性别特异性的相互作用。
在这项回顾性队列分析中，我们评估了 UnitedHealth Group（UHG）的临床发现索赔数据库中的去识别索赔数据。如果患者符合以下条件，则有资格纳入研究：年龄在 18 岁或以上；患有 2 型糖尿病或肥胖症（根据索赔定义）；在 2019 年至少有 6 个月的连续参保；因 COVID-19 住院，经 PCR 证实、UHG 手动病历审查或医院向 UHG 报告。主要结局是 COVID-19 院内死亡率。我们感兴趣的自变量是在家使用二甲双胍，定义为入院前一年中有 90 天以上的用药记录。协变量包括合并症、药物、人口统计学和州。通过性别评估效果的异质性。对于 Cox 比例风险模型，在 2020 年 6 月 7 日前基于入院后的索赔进行截尾，采用最佳结局法。采用倾向匹配的混合效应逻辑回归，按二甲双胍使用情况分层。
2020 年 1 月 1 日至 6 月 7 日期间，从药房索赔数据中筛选出 15380 名符合条件的患者，其中 6256 名（40.8%）为女性。在男女混合样本中，Cox 比例风险分层模型（风险比 [HR]0.887[95%CI 0.782-1.008]）或倾向匹配（比值比 [OR]0.912[95%CI 0.777-1.071]，p=0.15）均显示二甲双胍的使用与死亡率无显著降低。在女性中，Cox 比例风险模型（HR 0.785，95%CI 0.650-0.951）和倾向匹配（OR 0.759，95%CI 0.601-0.960，p=0.021）均显示二甲双胍与死亡率降低相关。男性死亡率无显著降低（HR 0.957，95%CI 0.82-1.14；p=0.689，Cox 比例风险）。
在因 COVID-19 住院的肥胖症或 2 型糖尿病女性中，二甲双胍与死亡率降低显著相关。需要进行前瞻性研究以了解其机制和因果关系。如果研究结果具有可重复性，那么二甲双胍可以广泛用于预防 COVID-19 死亡，因为它安全且价格低廉。
美国国立心肺血液研究所；医疗保健研究与质量局；患者中心结果研究所；明尼苏达州学习健康系统辅导培训计划，M 健康明尼阿波利斯机构资金；国家转化医学科学中心；和美国国家癌症研究所。
