Metformin therapy and severity and mortality of SARS-CoV-2 infection: a meta-analysis

Abstract

background. It has been postulated that metformin could have anti-SARS-CoV-2 action. this raises the hypothesis that people who take metformin may have lower SARS-CoV-2 severity and/or mortality. Objectives. to conduct a meta-analysis of the association between the use of Metformin and risk of severity and mortality in SARS-CoV-2 infection. Methods. We searched PubMed, EMbASE, Google scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv and Research Square) for studies published between December 2019 and January 2021. Data was extracted on study location, year of publication, design, number of participants, sex, age at baseline, body mass index, and exposure and outcome definition. Effect statistics were pooled using random effects models with 95% confidence intervals (CI). the quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS). Results. thirty-two observational studies were included, combining to a total sample of 44306 participants. the mean NOS score of included studies was 7.9. Results suggested that metformin use was associated with a reduced risk of SARS-CoV-2 mortality (OR = 0.56, 95% CI: 0.46-0.68, P < 0.001; 22 studies) but not with disease severity (OR = 0.85, 95% CI: 0.71-1.02, P = 0.077; 15 studies). In the subgroup analysis, metformin reduces the risk of mortality (OR = 0.69, 95% CI: 0.55-0.88; P = 0.002) and severity (OR = 0.83, 95% CI: 0.70-0.97, P = 0.023) in patients aged 70 and above. Conclusions. the use of metformin was associated to lower risk of mortality from SARS-CoV-2 infection. this association does not imply causation and further research is required to clarify potential mechanisms.

Does Metformin Decrease Mortality in Patients with Type 2 Diabetes Mellitus Hospitalized for COVID-19? A Multivariable and Propensity Score-adjusted Meta-analysis

“…We also used extractable raw data instead of pre-calculated ORs or HRs to determine the pooled OR for the unadjusted analysis. We found that there was a significant reduction of in-hospital mortality with outpatient or inpatient metformin therapy in patients with type 2 diabetes mellitus hospitalized for COVID-19 in the unadjusted analysis, which is in line with previous meta-analyses [39][40][41]. Furthermore, evidence obtained from observational studies is an of great importance source for clinical practice where randomized clinical trials are unavailable or infeasible [42].…”

“…To further compare and integrate the results of different studies and to increase statistical power, we set out to perform a meta-analysis. Prior to this meta-analysis, several meta-analyses [39][40][41] of the association between metformin therapy and severity and mortality were published, but they have issues. First, metformin therapy was not differentiated between outpatient and inpatient use, as oral hypoglycemic medications including metformin are usually held during hospitalization.…”

Is metformin use associated with low mortality in patients with type 2 diabetes mellitus hospitalized for COVID-19? a multivariable and propensity score-adjusted meta-analysis

“…We also used extractable raw data instead of pre-calculated ORs or HRs to determine the pooled OR for the unadjusted analysis. We found that there was a significant association between the reduction of in-hospital mortality and outpatient or inpatient metformin therapy for type 2 diabetes mellitus in COVID-19 patients in the unadjusted analysis, which is in line with previous meta-analyses [43][44][45]. Furthermore, evidence obtained from observational studies is an of great importance source for clinical practice where randomized clinical trials are unavailable or infeasible [46].…”

“…Prior to this meta-analysis, several meta-analyses [43][44][45] of the association between metformin therapy and severity and mortality were published, but they have issues. First, metformin therapy was not differentiated between outpatient and inpatient use, as oral hypoglycemic medications including metformin are usually held during hospitalization.…”

Preadmission use of antidiabetic medications and mortality among patients with COVID-19 having type 2 diabetes: A meta-analysis

“…We next compared our results with those from other publications [4][5][6][7][73][74][75][76][77][78][79][80][81][82][83][84][85][86][87][88]. No published meta-analysis has analyzed the association between TZD or AGI and COVID-19-related mortality (Table 4).…”