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.

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 in-hospital 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). CONCLUSIONS: 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.

Metformin is associated with favorable outcomes in patients with COVID-19 and type 2 diabetes mellitus.

Coronavirus disease 2019 (COVID-19) is a new pandemic the entire world is facing since December of 2019. Several risk factors are identified in developing severe disease and one of which is preexisting type 2 diabetes mellitus. Metformin is known to have host-directed anti-viral and anti-inflammatory properties. However, whether these effects offer lower mortality remains unclear. In this retrospective study, we aim to address whether metformin use prior to admission decreases mortality in patients with COVID-19 and pre-existing type 2 diabetes mellitus. A total of 1356 hospitalized patients with COVID-19 and pre-existing type 2 diabetes mellitus was analyzed by multivariable regression. Covariates that potentially confound the association were further adjusted using propensity score matching or inverse probability of treatment weighting. We found that metformin therapy prior to admission in patients with COVID-19 and type 2 diabetes mellitus was significantly associated with less primary outcome events including in-hospital mortality and hospice care enrollment with an odds ratio (OR) of 0.25 (95% CI 0.06-0.74) and less in-hospital length of stay, compared to the non-metformin group. Our results provide supporting evidence that metformin may confer increased survival in patients with COVID-19 and type 2 diabetes mellitus treated with metformin prior to hospitalization.