Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: A retrospective cohort study.
Ontology highlight
ABSTRACT: Aims
To determine the association between metformin use and mortality and ARDS incidence in patients with COVID-19 and type 2 diabetes.Methods
This study was a multi-center retrospective analysis of COVID-19 patients with type 2 diabetes and admitted to four hospitals in Hubei province, China from December 31st, 2019 to March 31st, 2020. Patients were divided into two groups according to their exposure to metformin during hospitalization. The outcomes of interest were 30-day all-cause mortality and incidence of ARDS. We used mixed-effect Cox model and random effect logistic regression to evaluate the associations of metformin use with outcomes, adjusted for baseline characteristics.Results
Of 328 patients with COVID-19 and type 2 diabetes included in the study cohort, 30.5% (100/328) were in the metformin group. In the mixed-effected model, metformin use was associated with the lower incidence of ARDS. There was no significant association between metformin use and 30-day all-cause mortality. Propensity score-matched analysis confirmed the results. In the subgroup analysis, metformin use was associated with the lower incidence of ARDS in females.Conclusions
Metformin may have potential benefits in reducing the incidence of ARDS in patients with COVID-19 and type 2 diabetes. However, this benefit differs significantly by gender.
SUBMITTER: Jiang N
PROVIDER: S-EPMC7833191 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
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.
| S-EPMC7832552 | biostudies-literature
Project description: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.
| S-EPMC7537216 | biostudies-literature
Project description:BackgroundThe impact of obesity on outcomes in acute respiratory distress syndrome (ARDS) is not well understood and remains controversial. Recent studies suggest that obesity might be associated with higher morbidity and mortality in respiratory disease caused by SARS-CoV-2 (COVID-19 disease). Our objective was to evaluate the association between obesity and hospital mortality in critical COVID-19 patients.MethodsWe conducted a retrospective cohort study in a tertiary academic center located in Montréal between March and August 2020. We included all consecutive adult patients admitted to the ICU for COVID-19-confirmed respiratory disease. Our main outcome was hospital mortality. We estimated the association between obesity, using the body mass index as a continuous variable, and hospital survival by fitting a multivariable Cox proportional hazards model.ResultsWe included 94 patients. Median [q1, q3] body mass index (BMI) was 29 [26-32] kg/m2 and 37% of patients were obese (defined as BMI > 30 kg/m2). Hospital mortality for the entire cohort was 33%. BMI was significantly associated with hospital mortality (hazard ratio [HR] = 2.49 per 10 units BMI; 95% CI, from 1.69 to 3.70; p < 0.001) even after adjustment for sex, age and obesity-related comorbidities (adjusted HR = 3.50; 95% CI from 2.03 to 6.02; p < 0.001).ConclusionsObesity was prevalent in hospitalized patients with critical illness secondary to COVID-19 disease and a higher BMI was associated with higher hospital mortality. Further studies are needed to validate this association and to better understand its underlying mechanisms.
| S-EPMC8385700 | biostudies-literature
Project description:AimsThe relationship between metformin therapy and the risk of coronavirus disease (COVID-19) has not been reported among patients with type 2 diabetes mellitus (DM). We aimed to investigate whether metformin therapy was associated with the incidence of COVID-19 among type 2 DM patients in South Korea.MethodsThe National Health Insurance Service-COVID-19 cohort database, comprising COVID-19 patients from 1 January 2020 to 4 June 2020, was used for this study. Among them, adult patients with type 2 DM were included in this study. Metformin users were defined as those who had been prescribed continuous oral metformin for over a period of???90 days, and the control group was defined as all other patients.ResultsOverall, 27,493 patients with type 2 DM (7204, metformin user group; 20,289, control group) were included. After propensity score matching, 11,892 patients (5946 patients in each group) were included in the final analysis. In the logistic regression analysis, the odds of metformin users developing COVID-19 was 30% lower than that of the control group [odds ratio (OR): 0.70, 95% confidence interval (CI): 0.61-0.80; P?<?0.001]. However, in the multivariate model, metformin use was not associated with hospital mortality when compared with that of the control group (OR: 1.26, 95% CI: 0.81-1.95; P?=?0.301).ConclusionsMetformin therapy might have potential benefits for the prevention of COVID-19 among patients with type 2 DM in South Korea. However, it did not affect the hospital mortality of type 2 DM patients diagnosed with COVID-19.
| S-EPMC7882044 | biostudies-literature
Project description:AimsType 2 diabetes is considered to be one of the essential risks of adverse outcomes in coronavirus disease 2019 (COVID-19).1 Metformin and insulin were suggested to affect the outcomes. However, divergent views are still expressed. We aim to gain further insight into metformin and insulin in both pre-admission and in-hospital usage in COVID-19 patients with pre-existed type 2 diabetes.Main methodsThis is a multicentral retrospective study of the hospital confirmed COVID-19 patients between January 19 to April 09, 2020, who admitted to 3 main hospitals in Xiangyang city, China. The effect of type 2 diabetes, metformin, and insulin on COVID-19 were analyzed, respectively. Clinical characteristics, blood laboratory indices, clinical observational indices, and outcomes of these cases were collected.Key findingsA total of 407 confirmed COVID-19 patients (including 50 pre-existed type 2 diabetes) were eligible in our study. COVID-19 patients with type 2 diabetes had more adverse outcomes than non-diabetes (OR2: mortality: 1.46 [95% CI3 1.11, 1.93]; P < 0.001). Pre-admission metformin usage showed a declined intensive care unit admission rate in a dose-dependent fashion (OR 0.04 [95% CI 0.00, 0.99]; adjust P = 0.049). While in-hospital insulin usage attempted to increase the invasive ventilation (8 [34.8%] vs. 1 [3.7%], adjust P = 0.043), independent of age and blood glucose.SignificanceOur study indicated that pre-admitted metformin usage may have beneficial effects on COVID-19 with pre-existed type 2 diabetes, insulin should be used sparingly in the hospital stay.
| S-EPMC7972834 | biostudies-literature
Project description:Many factors influence whether the first-line oral anti-diabetic drug, metformin, should be initiated to a patient with type 2 diabetes mellitus (T2DM) early in the course of management in addition to lifestyle modifications. This study aims to evaluate the net effects of metformin monotherapy (MM) on the all-cause mortality and cardiovascular disease (CVD) events.A retrospective 5-year follow-up cohort study was conducted on Chinese adult patients with T2DM and without any CVD history under public primary care. Cox proportional hazard regressions were performed to compare the risk of all-cause mortality and CVD events (CHD, stroke, heart failure) between patients receiving lifestyle modifications plus MM (MM groups) and those with lifestyle modifications alone (control groups).3400 pairs of matched patients were compared. MM group had an incidence rate of 7.5 deaths and 11.3 CVD events per 1000 person-years during a median follow-up period of 62.5 months whereas control group had 11.1 deaths and 16.3 per 1000 person-years during a median follow-up period of 43.5-44.5 months. MM group showed a 29.5 and 30-35% risk reduction of all-cause mortality and CVD events (except heart failure) than control group (P < 0.001). MM group was more prone to progress to chronic kidney disease but this was not statistically significant.Type 2 diabetic patients who were started on metformin monotherapy showed improvement in many of the clinical parameters and a reduction in all-cause mortality and CVD events than lifestyle modifications alone. If there is no contraindication and if tolerated, diabetic patients should be prescribed with metformin early in the course of the diabetic management to minimize their risk of having the cardiovascular events and mortality in the long run.
| S-EPMC4600251 | biostudies-literature
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.
| S-EPMC8397144 | biostudies-literature
Project description:Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk-factor for severe disease. Inflammation is central to the aetiology of both conditions where immune responses influence disease course. Identifying at-risk groups through immuno-inflammatory signatures can direct personalised care and help develop potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leukocyte populations in circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia, of CD8+ lymphocytes, was associated with severe COVID-19 and intensive care admission in non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia of classical monocytes were specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Over-expression of inflammatory markers reminiscent of the type-1 interferon pathway underlaid the immunophenotype associated with T2D. These changes may contribute to severity of COVID-19 in T2D. These findings show characteristics of severe COVID-19 in T2D as well as provide evidence that type-1 interferons may be actionable targets for future studies.
| S-SCDT-EMM-2020-13038 | biostudies-other
Project description:Aims:To describe discontinuation and adherence to metformin in the United Kingdom. Methods:This was a retrospective analysis of data from the Clinical Practice Research Datalink database of type 2 diabetes patients aged ?18 years with ?1 metformin prescription in 2013. Metformin use was assessed in new and ongoing users, defined, respectively, as not having or having a prescription for metformin in the baseline period. Discontinuation was assessed in all patients and adherence in patients who did not discontinue metformin. Factors predictive of discontinuation and adherence were assessed. Results:Discontinuation among new and ongoing users was 35.9% and 23.1%, respectively. Among the continuers of metformin treatment, the adherence rate was 40.5% and 44.3% among new and ongoing users, respectively. Among new users, baseline use of DDP-4 inhibitors (HR 1.276) and diabetes duration (HR 1.013) were associated with an increased risk of discontinuation, whereas increased age (HR 0.997), concomitant lipid-lowering therapy (HR 0.956), macrovascular disease (HR 0.952), and chronic kidney disease (HR 0.952) were associated with a decreased risk of discontinuation among ongoing users. Variables positively associated with adherence in both user groups were (HR values for all patients) age (1.021), smoking status (1.188), and baseline comorbidities: chronic kidney disease, depression, dementia, and chronic obstructive pulmonary disease (1.106, 1.192, 2.27, and 1.211, respectively), while obesity (0.936) and HbA1c 8.0-8.9% (0.862; reference <6.5%) were negatively associated with adherence. Conclusions:About one-third of patients initiating metformin discontinued within 12 months and fewer than 50% of all patients are adherent to metformin.
| S-EPMC7240214 | biostudies-literature
Project description:Several descriptive studies have reported that higher neutrophil count (NC) may be correlated with poor prognosis in patients with confirmed COVID-19 infection. However, the findings from these studies are limited by methodology and data analysis. This study is a cohort study. We nonselectively and consecutively collected a total of 663 participants in a Chinese hospital from January 7 to February 28. Standardized and two-piecewise Cox regression model were employed to evaluate the association between baseline neutrophil count (bNC), neutrophil count change rate (NCR), and death. bNC had a U-shaped association with death. In the range of 0.1 to ≤1.49 × 109 /L (hazard ratio [HR] = 0.19, 95% confidence interval [CI] = 0.05-0.66) and >3.55 × 109 /L of bNC (HR = 2.82, 95% CI = 1.19-6.67), the trends on bNC with mortality were opposite. By recursive algorithm, the bNC at which the risk of the death was lower in the range of >1.49 to ≤3.55 × 109 /L (HR = 13.64, 95% CI = 0.25-74.71). In addition, we find that NCRs (NCR1 and NCR2) are not associated with COVID-19-related deaths. Compared with NCR, bNC has the potential to be used for early risk stratification in patients with COVID-19 infection. The relationship between bNC and mortality was U-shaped. The safe range of bNC was 1.64-4.0 × 109 /L. Identifying the correlation may be helpful for early risk stratification and medical decision-making.
| S-EPMC8014534 | biostudies-literature