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
Zhiyuan Ma, Mahesh Krishnamurthy
PLOS ONE, doi:10.1371/journal.pone.0282210
Background Coronavirus disease 2019 (COVID-19) is a new pandemic that the entire world is facing since December of 2019. Increasing evidence has shown that metformin is linked to favorable outcomes in patients with COVID-19. The aim of this study was to address whether outpatient or inpatient metformin therapy for type 2 diabetes mellitus is associated with low inhospital mortality in patients hospitalized for COVID-19.
Methods We searched studies published in PubMed, Embase, Google Scholar and Cochrane Library up to November 1, 2022. Raw event data extracted from individual study were pooled using the Mantel-Haenszel approach. Odds ratio (OR) or hazard ratio (HR) adjusted for covariates that potentially confound the association using multivariable regression or propensity score matching was pooled by the inverse-variance method. Random effect models were applied for meta-analysis due to variance among studies.
Results Twenty-two retrospective observational studies were selected. The pooled unadjusted OR for outpatient metformin therapy and in-hospital mortality was 0.48 (95% CI, 0.37-0.62) and the pooled OR adjusted with multivariable regression or propensity score matching was 0.71 (95% CI, 0.50-0.99). The pooled unadjusted OR for inpatient metformin therapy and in-hospital mortality was 0.18 (95% CI, 0.10-0.31), whereas the pooled adjusted HR was 1.10 (95% CI, 0.38-3.15).
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'abstract': '<jats:sec id="sec001">\n'
'<jats:title>Background</jats:title>\n'
'<jats:p>Coronavirus disease 2019 (COVID-19) is a new pandemic that the entire world is facing '
'since December of 2019. Increasing evidence has shown that metformin is linked to favorable '
'outcomes in patients with COVID-19. The aim of this study was to address whether outpatient '
'or inpatient metformin therapy for type 2 diabetes mellitus is associated with low '
'in-hospital mortality in patients hospitalized for COVID-19.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec002">\n'
'<jats:title>Methods</jats:title>\n'
'<jats:p>We searched studies published in PubMed, Embase, Google Scholar and Cochrane Library '
'up to November 1, 2022. Raw event data extracted from individual study were pooled using the '
'Mantel-Haenszel approach. Odds ratio (OR) or hazard ratio (HR) adjusted for covariates that '
'potentially confound the association using multivariable regression or propensity score '
'matching was pooled by the inverse-variance method. Random effect models were applied for '
'meta-analysis due to variance among studies.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec003">\n'
'<jats:title>Results</jats:title>\n'
'<jats:p>Twenty-two retrospective observational studies were selected. The pooled unadjusted '
'OR for outpatient metformin therapy and in-hospital mortality was 0.48 (95% CI, 0.37–0.62) '
'and the pooled OR adjusted with multivariable regression or propensity score matching was '
'0.71 (95% CI, 0.50–0.99). The pooled unadjusted OR for inpatient metformin therapy and '
'in-hospital mortality was 0.18 (95% CI, 0.10–0.31), whereas the pooled adjusted HR was 1.10 '
'(95% CI, 0.38–3.15).</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec004">\n'
'<jats:title>Conclusions</jats:title>\n'
'<jats:p>Our results suggest that there is a significant association between the reduction of '
'in-hospital mortality and outpatient metformin therapy for type 2 diabetes mellitus in '
'patients hospitalized for COVID-19.</jats:p>\n'
'</jats:sec>',
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