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Risk of Metformin in Patients With Type 2 Diabetes With COVID-19: A Preliminary Retrospective Report.

ABSTRACT: The current outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread across the world. No specific antiviral agents have been adequately evidenced for the treatment of coronavirus disease 2019 (COVID-19). Although metformin has been recommended as a host-directed therapy for COVID-19, there are some opposite views. The effects of metformin on the disease severity of patients with COVID-19 with diabetes during hospitalization remains unclear. This study aimed to determine the effect of metformin on disease severity. We enrolled 110 hospitalized patients with COVID-19 with diabetes prescribed either metformin or non-metformin hypoglycemic treatment for a case-control study. The primary outcome was the occurrence of life-threatening complications. There were no differences between the two groups in age, sex, comorbidities, and clinical severity at admission. Blood glucose and lactate dehydrogenase levels of the metformin group were higher than those of the non-metformin group at admission. Other laboratory parameters at admission and treatments after admission were not different between the two groups. Strikingly, the percentage of patients who experienced life-threatening complications was significantly higher in the metformin group (28.6% (16/56) vs. 7.4% (4/54), P = 0.004). Antidiabetic therapy with metformin was associated with a higher risk of disease progression in patients with COVID-19 with diabetes during hospitalization (adjusted odds ratio = 3.964, 95% confidence interval 1.034-15.194, P = 0.045). This retrospective analysis suggested a potential safety signal for metformin, the use of which was associated with a higher risk of severe COVID-19. We propose that metformin withdrawal in patients with COVID-19 be considered to prevent disease progression.

SUBMITTER: Gao Y

PROVIDER: S-EPMC7537216 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundType 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.MethodsIn 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.Findings6256 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).InterpretationMetformin 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.FundingNational 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.

Project description:The coronavirus disease 2019 (COVID-19) increases hyperinflammatory state, leading to acute lung damage, hyperglycemia, vascular endothelial damage, and a higher mortality rate. Metformin is a first-line treatment for type 2 diabetes and is known to have anti-inflammatory and immunosuppressive effects. Previous studies have shown that metformin use is associated with decreased risk of mortality among patients with COVID-19; however, the results are still inconclusive. This study investigated the association between metformin and the risk of mortality among diabetes patients with COVID-19. Data were collected from online databases such as PubMed, EMBASE, Scopus, and Web of Science, and reference from the most relevant articles. The search and collection of relevant articles was carried out between 1 February 2020, and 20 June 2021. Two independent reviewers extracted information from selected studies. The random-effects model was used to estimate risk ratios (RRs), with a 95% confidence interval. A total of 16 studies met all inclusion criteria. Diabetes patients given metformin had a significantly reduced risk of mortality (RR, 0.65; 95% CI: 0.54-0.80, p < 0.001, heterogeneity I2 = 75.88, Q = 62.20, and τ2 = 0.06, p < 0.001) compared with those who were not given metformin. Subgroup analyses showed that the beneficial effect of metformin was higher in the patients from North America (RR, 0.43; 95% CI: 0.26-0.72, p = 0.001, heterogeneity I2 = 85.57, Q = 34.65, τ2 = 0.31) than in patients from Europe (RR, 0.67; 95% CI: 0.47-0.94, p = 0.02, heterogeneity I2 = 82.69, Q = 23.11, τ2 = 0.10) and Asia (RR, 0.90; 95% CI: 0.43-1.86, p = 0.78, heterogeneity I2 = 64.12, Q = 11.15, τ2 = 0.40). This meta-analysis shows evidence that supports the theory that the use of metformin is associated with a decreased risk of mortality among diabetes patients with COVID-19. Randomized control trials with a higher number of participants are warranted to assess the effectiveness of metformin for reducing the mortality of COVID-19 patients.

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Risk of Metformin in Patients With Type 2 Diabetes With COVID-19: A Preliminary Retrospective Report.

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