Metformin Use Is Associated with Decreased Mortality in COVID-19 Patients with Diabetes: Evidence from Retrospective Studies and Biological Mechanism

Background and Aims: 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. Methods: 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. Results: 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). Conclusion: 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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Glucagon-like peptide-1 mimetics, optimal for Asian type 2 diabetes patients with and without overweight/obesity: meta-analysis of randomized controlled trials

Scientific Reports ◽

10.1038/s41598-017-16018-9 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 4

Author(s):

Fang Zhang ◽

Lizhi Tang ◽

Yuwei Zhang ◽

Qingguo Lü ◽

Nanwei Tong

Keyword(s):

Type 2 Diabetes ◽

Randomized Controlled Trials ◽

Meta Analysis ◽

Controlled Trials ◽

Randomized Controlled ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Diabetes Patients

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Meta-analysis of the insulin dosage in Chinese type 2 diabetes patients receiving insulin treatment

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(16)31453-x ◽

2016 ◽

Vol 120 ◽

pp. S196

Author(s):

Xiaoling Cai ◽

Wenjia Yang ◽

Xueying Gao ◽

Lingli Zhou ◽

Xueyao Han ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Treatment ◽

Meta Analysis ◽

Insulin Dosage ◽

Diabetes Patients

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The Association of Coagulation Indicators and Coagulant Agents With 30-Day Mortality of Critical Diabetics

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/10760296211026385 ◽

2021 ◽

Vol 27 ◽

pp. 107602962110263

Author(s):

Yingxin Huang ◽

Zhihua Zhong ◽

Fanna Liu

Keyword(s):

Subgroup Analysis ◽

Medical Information ◽

Cardiovascular Effects ◽

World Health ◽

Coagulation System ◽

Hospital Death ◽

Hazard Regression ◽

Risk Of Mortality ◽

Patients With Diabetes ◽

Diabetes Patients

Diabetes, regarded as a global health concerned disease, was focused by the World Health Organization (WHO). Patients with diabetes may have a hypercoagulable and hypo-fibrinolysis state. There is lots of research about cardiovascular effects on diabetes patients, but less about the coagulation system. This study is designed to investigate the relationship between coagulation indicators and 30-day mortality of critical diabetes patients. In this retrospective, single-center study, we included adult patients diagnosed with diabetes. Data, including demographic, complication, laboratory tests, scoring system, and anticoagulant treatment, were extracted from Medical Information Mart for Intensive Care (MIMIC-III). The receiver operating characteristic (ROC) curve and Kaplan-Meier curve were applied to predict the association of mortality and coagulation indicators. Cox hazard regression model and subgroup analysis were used to analyze the risk factors associated with 30-day mortality. A total of 4026 patients with diabetes mellitus were included in our study, of whom 3312 survived after admitted to the hospital and 714 died. Cox hazard regression showed anticoagulant therapy might decrease the risk of 30-day mortality after adjusted. In age <70 subgroup analysis, we found that patients with PTT <26.8 s or lightly increased PT may increase odds of 30-day hospital death (HR, 95%CI, 2.044 (1.376, 3.034), 1.562 (1.042, 2.343)). When age >70, lightly increased PTT may reduce the risk of mortality, but PT >16.3 s, a high level of hypo-coagulation state, increase risk of mortality (HR, 95%CI, 0.756 (0.574, 0.996), 1.756 (1.129, 2.729)). Critical diabetes patients may benefit from anticoagulant agents. The abnormal coagulant function is related to the risk of 30-day mortality.

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Sitagliptin improves vascular endothelial function in Japanese type 2 diabetes patients without cardiovascular disease

Journal of Diabetes Mellitus ◽

10.4236/jdm.2012.23053 ◽

2012 ◽

Vol 02 (03) ◽

pp. 338-345 ◽

Cited By ~ 8

Author(s):

Kazunari Suzuki ◽

Kentaro Watanabe ◽

Tatsuya Suzuki ◽

Motoshi Ouchi ◽

Shoko Futami-Suda ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Endothelial Function ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

Diabetes Patients

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PCN11 Decreased Risk of Prostate Cancer in Type 2 Diabetes Patients: A Meta-Analysis of Cohort Studies

Value in Health ◽

10.1016/j.jval.2012.08.309 ◽

2012 ◽

Vol 15 (7) ◽

pp. A655

Author(s):

B. Dipika ◽

K. Gudala ◽

K. Undela ◽

T. Pramil ◽

A. Bhansali

Keyword(s):

Prostate Cancer ◽

Type 2 Diabetes ◽

Cohort Studies ◽

Meta Analysis ◽

Diabetes Patients

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Association of VEGF Gene Polymorphisms with Susceptibility to Diabetic Retinopathy: A Systematic Review and Meta-Analysis

Hormone and Metabolic Research ◽

10.1055/a-1143-6024 ◽

2020 ◽

Vol 52 (05) ◽

pp. 264-279

Author(s):

Xiaorong Li ◽

Juping Liu ◽

Qianhui Yang ◽

Yan Zhang ◽

Xiaomin Zhang

Keyword(s):

Diabetic Retinopathy ◽

Gene Polymorphisms ◽

Meta Analysis ◽

Vascular Endothelial ◽

Nucleotide Polymorphisms ◽

Vegf Gene ◽

Asian Populations ◽

Increased Risk ◽

Endothelial Growth Factor

AbstractThe associations between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of type 2 diabetic retinopathy (DR) – proliferative diabetic retinopathy (PDR), and nonproliferative diabetic retinopathy (NPDR) – remain unclear. A systematic search and meta-analysis using odds ratio (OR) with 95% confidence interval (CI) was performed to evaluate the association. Our study concluded 26 studies containing 10 single nucleotide polymorphisms (SNPs). In Asian populations, rs3025039 polymorphism was associated with DR risk, while in overall populations and Caucasians, the DR risk was increased by association with rs2010963. There was a significant association between rs25648 and rs833061 and DR risk in Caucasians. DR risks were found to be significantly associated between rs3025021, rs13207351, and rs2146323 in either overall populations, Caucasians or Asians. Besides, in overall and Asian populations, rs699947 and rs3025039 were associated with PDR risk. rs1570360, rs3025039, and rs833061 played a key role in PDR etiology in Caucasians. rs2010963 was associated with increased risk of PDR in overall populations. A significant association between rs699947, rs3025039, and rs833061 and NPDR risk in overall populations and Asians was found. A significant association was observed between rs2010963 and increased NPDR risk in overall and Caucasian populations. This study provides a new insight into the parthenogenesis of diabetic retinopathy. Targeting VEGF SNPs may be a potential of therapeutic approach for the treatment of DR, PDR, and NPDR.

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Plasma levels of von Willebrand factor in type 2 diabetes patients with and without cardiovascular diseases: A meta‐analysis

Diabetes/Metabolism Research and Reviews ◽

10.1002/dmrr.3193 ◽

2019 ◽

Vol 36 (1) ◽

Cited By ~ 3

Author(s):

Xun Peng ◽

Xia Wang ◽

Mengge Fan ◽

Junyu Zhao ◽

Liao Lin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Diseases ◽

Von Willebrand Factor ◽

Plasma Levels ◽

Meta Analysis ◽

Von Willebrand ◽

Willebrand Factor ◽

Diabetes Patients

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Aspirin for primary prevention of cardiovascular outcomes in diabetes mellitus: An updated systematic review and meta-analysis

European Journal of Preventive Cardiology ◽

10.1177/2047487319825510 ◽

2019 ◽

Vol 27 (19) ◽

pp. 2034-2041 ◽

Cited By ~ 2

Author(s):

Safi U Khan ◽

Zain Ul Abideen Asad ◽

Muhammad U Khan ◽

Swapna Talluri ◽

Farman Ali ◽

...

Keyword(s):

Diabetes Mellitus ◽

Cardiovascular Disease ◽

Primary Prevention ◽

Meta Analysis ◽

Cardiovascular Outcomes ◽

Randomized Controlled ◽

Patients With Diabetes ◽

Incident Cases ◽

Risk Ratios ◽

Prevention Of Cardiovascular Disease

Background The safety and efficacy of aspirin for the primary prevention of cardiovascular disease in patients with diabetes mellitus remains controversial. Design A meta-analysis to investigate the effects of aspirin for the prevention of cardiovascular disease in diabetes mellitus. Methods Ten randomized controlled trials were selected using MEDLINE, EMBASE and CENTRAL databases until 27 September 2018. Risk ratios (RRs) with 95% confidence intervals (CIs) and risk differences (RDs) reported as incident events per 1000 person-years were calculated. Results In 33,679 patients, aspirin did not significantly reduce the risk of major adverse cardiovascular outcomes (RR 0.93, 95% CI 0.87–1.00, P = 0.06; RD −0.68 incident cases per 1000 person-years (95% CI −1.54, 0.17)), cardiovascular mortality (RR 0.95, 95% CI 0.83–1.09, P = 0.49; RD 0.11 incident cases per 1000 person-years (95% CI −0.80, 1.02)), myocardial infarction (RR 0.91, 95% CI 0.75–1.11, P = 0.36; RD −0.66 incident cases per 1000 person-years (95% CI −2.07, 0.75)), or stroke (RR 0.91, 95% C, 0.76–1.10, P = 0.33; RD −0.55 incident cases per 1000 person-years (95% CI −1.57, 0.47)). There was a significantly higher risk of total bleeding associated with aspirin (RR 1.29, 95% CI 1.07–1.55, P = 0.01; RD 1.49 incident cases per 1000 person-years (95% CI 0.36, 2.61)). Conclusion The use of aspirin for primary prevention of cardiovascular disease in patients with diabetes mellitus increases the risk of total bleeding without reducing the risk of major adverse cardiovascular outcomes.

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