Risk of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Among Patients with Type 2 Diabetes Mellitus on Anti-Hyperglycemic Medications

IF 3.4 2区医学 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

Clinical Epidemiology Pub Date : 2024-05-31 DOI:10.2147/clep.s458901

Oluwasolape Olawore, Lindsey E Turner, Michael D Evans, Steven G Johnson, Jared D Huling, Carolyn T Bramante, John B Buse, Til Stürmer

{"title":"Risk of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Among Patients with Type 2 Diabetes Mellitus on Anti-Hyperglycemic Medications","authors":"Oluwasolape Olawore, Lindsey E Turner, Michael D Evans, Steven G Johnson, Jared D Huling, Carolyn T Bramante, John B Buse, Til Stürmer","doi":"10.2147/clep.s458901","DOIUrl":null,"url":null,"abstract":"Background: Observed activity of metformin in reducing the risk of severe COVID-19 suggests a potential use of the anti-hyperglycemic in the prevention of post-acute sequelae of SARS-CoV-2 infection (PASC). We assessed the 3-month and 6-month risk of PASC among patients with type 2 diabetes mellitus (T2DM) comparing metformin users to sulfonylureas (SU) or dipeptidyl peptidase-4 inhibitors (DPP4i) users. Methods: We used de-identified patient level electronic health record data from the National Covid Cohort Collaborative (N3C) between October 2021 and April 2023. Participants were adults ≥ 18 years with T2DM who had at least one outpatient healthcare encounter in health institutions in the United States prior to COVID-19 diagnosis. The outcome of PASC was defined based on the presence of a diagnosis code for the illness or using a predicted probability based on a machine learning algorithm. We estimated the 3-month and 6-month risk of PASC and calculated crude and weighted risk ratios (RR), risk differences (RD), and differences in mean predicted probability. Results: We identified 5596 (mean age: 61.1 years; SD: 12.6) and 1451 (mean age: 64.9 years; SD 12.5) eligible prevalent users of metformin and SU/DPP4i respectively. We did not find a significant difference in risk of PASC at 3 months (RR = 0.86 [0.56; 1.32], RD = − 3.06 per 1000 [− 12.14; 6.01]), or at 6 months (RR = 0.81 [0.55; 1.20], RD = − 4.91 per 1000 [− 14.75, 4.93]) comparing prevalent users of metformin to prevalent users of SU/ DPP4i. Similar observations were made for the outcome definition using the ML algorithm. Conclusion: The observed estimates in our study are consistent with a reduced risk of PASC among prevalent users of metformin, however the uncertainty of our confidence intervals warrants cautious interpretations of the results. A standardized clinical definition of PASC is warranted for thorough evaluation of the effectiveness of therapies under assessment for the prevention of PASC. Plain Language Summary: Previous research suggests that metformin, due to its anti-viral, anti-inflammatory, and anti-thrombotic properties may reduce the risk of severe COVID-19. Given the shared etiology of COVID-19 and the post-acute sequelae of SARS-CoV-2 (PASC), and the proposed inflammatory processes of PASC, metformin may also be a beneficial preventive option. We investigated the benefit of metformin for PASC prevention in a population of type 2 diabetes mellitus patients with a COVID-19 diagnosis who were on metformin or two other anti-hyperglycemic medications prior to infection with SARS-CoV-2. Our results were consistent with a reduction in the risk of PASC with the use of metformin, however, the imprecise confidence intervals obtained warrants further investigation of this association of the potential beneficial effect of metformin for preventing PASC in patients with medication-managed diabetes. ","PeriodicalId":10362,"journal":{"name":"Clinical Epidemiology","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Epidemiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/clep.s458901","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Observed activity of metformin in reducing the risk of severe COVID-19 suggests a potential use of the anti-hyperglycemic in the prevention of post-acute sequelae of SARS-CoV-2 infection (PASC). We assessed the 3-month and 6-month risk of PASC among patients with type 2 diabetes mellitus (T2DM) comparing metformin users to sulfonylureas (SU) or dipeptidyl peptidase-4 inhibitors (DPP4i) users.
Methods: We used de-identified patient level electronic health record data from the National Covid Cohort Collaborative (N3C) between October 2021 and April 2023. Participants were adults ≥ 18 years with T2DM who had at least one outpatient healthcare encounter in health institutions in the United States prior to COVID-19 diagnosis. The outcome of PASC was defined based on the presence of a diagnosis code for the illness or using a predicted probability based on a machine learning algorithm. We estimated the 3-month and 6-month risk of PASC and calculated crude and weighted risk ratios (RR), risk differences (RD), and differences in mean predicted probability.
Results: We identified 5596 (mean age: 61.1 years; SD: 12.6) and 1451 (mean age: 64.9 years; SD 12.5) eligible prevalent users of metformin and SU/DPP4i respectively. We did not find a significant difference in risk of PASC at 3 months (RR = 0.86 [0.56; 1.32], RD = − 3.06 per 1000 [− 12.14; 6.01]), or at 6 months (RR = 0.81 [0.55; 1.20], RD = − 4.91 per 1000 [− 14.75, 4.93]) comparing prevalent users of metformin to prevalent users of SU/ DPP4i. Similar observations were made for the outcome definition using the ML algorithm.
Conclusion: The observed estimates in our study are consistent with a reduced risk of PASC among prevalent users of metformin, however the uncertainty of our confidence intervals warrants cautious interpretations of the results. A standardized clinical definition of PASC is warranted for thorough evaluation of the effectiveness of therapies under assessment for the prevention of PASC.

Plain Language Summary: Previous research suggests that metformin, due to its anti-viral, anti-inflammatory, and anti-thrombotic properties may reduce the risk of severe COVID-19. Given the shared etiology of COVID-19 and the post-acute sequelae of SARS-CoV-2 (PASC), and the proposed inflammatory processes of PASC, metformin may also be a beneficial preventive option. We investigated the benefit of metformin for PASC prevention in a population of type 2 diabetes mellitus patients with a COVID-19 diagnosis who were on metformin or two other anti-hyperglycemic medications prior to infection with SARS-CoV-2. Our results were consistent with a reduction in the risk of PASC with the use of metformin, however, the imprecise confidence intervals obtained warrants further investigation of this association of the potential beneficial effect of metformin for preventing PASC in patients with medication-managed diabetes.

查看原文本刊更多论文

服用降糖药物的 2 型糖尿病患者出现 SARS-CoV-2 感染急性后遗症 (PASC) 的风险

背景：观察到二甲双胍在降低严重 COVID-19 风险方面的活性，这表明这种抗高血糖药有可能用于预防 SARS-CoV-2 感染的急性后遗症（PASC）。我们将二甲双胍使用者与磺脲类药物（SU）或二肽基肽酶-4 抑制剂（DPP4i）使用者进行了比较，评估了 2 型糖尿病（T2DM）患者 3 个月和 6 个月的 PASC 风险：我们使用了 2021 年 10 月至 2023 年 4 月期间来自国家 Covid 队列协作组织 (N3C) 的去标识化患者级电子健康记录数据。参与者为≥18 岁的 T2DM 成人，他们在 COVID-19 诊断前至少在美国的医疗机构就诊过一次。PASC 的结果是根据是否存在疾病诊断代码或使用基于机器学习算法的预测概率来定义的。我们估算了 3 个月和 6 个月的 PASC 风险，并计算了粗略和加权风险比 (RR)、风险差异 (RD) 和平均预测概率差异：我们分别发现了 5596 名（平均年龄：61.1 岁；SD：12.6）和 1451 名（平均年龄：64.9 岁；SD：12.5）符合条件的二甲双胍和 SU/DPP4i 流行用户。我们没有发现二甲双胍的流行用户与 SU/DPP4i 的流行用户在 3 个月时的 PASC 风险（RR = 0.86 [0.56; 1.32]，RD = - 3.06 per 1000 [- 12.14; 6.01]）或 6 个月时的 PASC 风险（RR = 0.81 [0.55; 1.20]，RD = - 4.91 per 1000 [- 14.75, 4.93]）有明显差异。使用 ML 算法对结果定义也得出了类似的观察结果：我们研究中观察到的估计值与二甲双胍的普遍使用者发生 PASC 的风险降低相一致，但我们的置信区间存在不确定性，因此对结果的解释需要谨慎。需要对 PASC 进行标准化的临床定义，以便对正在评估的预防 PASC 的疗法的有效性进行全面评估。白话摘要：以往的研究表明，二甲双胍因其抗病毒、抗炎和抗血栓的特性，可降低严重 COVID-19 的风险。鉴于 COVID-19 和 SARS-CoV-2 后遗症（PASC）的病因相同，且 PASC 存在炎症过程，二甲双胍可能也是一种有益的预防选择。我们在确诊为 COVID-19 的 2 型糖尿病患者中调查了二甲双胍对预防 PASC 的益处，这些患者在感染 SARS-CoV-2 之前服用过二甲双胍或其他两种降糖药物。我们的研究结果表明，使用二甲双胍可降低PASC的发病风险，但由于置信区间不精确，因此需要进一步研究二甲双胍对药物治疗糖尿病患者预防PASC的潜在有益作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Clinical Epidemiology Medicine-Epidemiology

CiteScore

6.30

自引率

5.10%

发文量

169

审稿时长

16 weeks

期刊介绍： Clinical Epidemiology is an international, peer reviewed, open access journal. Clinical Epidemiology focuses on the application of epidemiological principles and questions relating to patients and clinical care in terms of prevention, diagnosis, prognosis, and treatment. Clinical Epidemiology welcomes papers covering these topics in form of original research and systematic reviews. Clinical Epidemiology has a special interest in international electronic medical patient records and other routine health care data, especially as applied to safety of medical interventions, clinical utility of diagnostic procedures, understanding short- and long-term clinical course of diseases, clinical epidemiological and biostatistical methods, and systematic reviews. When considering submission of a paper utilizing publicly-available data, authors should ensure that such studies add significantly to the body of knowledge and that they use appropriate validated methods for identifying health outcomes. The journal has launched special series describing existing data sources for clinical epidemiology, international health care systems and validation studies of algorithms based on databases and registries.