Dataset Information

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

ABSTRACT:

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).

Conclusions

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.

SUBMITTER: Poly TN

PROVIDER: S-EPMC8397144 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:INTRODUCTION: Metformin has anti-inflammatory and anti-thrombotic effects that may improve the outcome of critical illness, but clinical data are limited. We examined the impact of preadmission metformin use on mortality among intensive care unit (ICU) patients with type 2 diabetes. METHODS: We conducted this population-based cohort study among all persons admitted to the 17 ICUs in Northern Denmark (population approximately 1.8 million). We focused on all patients with type 2 diabetes who were admitted to the ICUs between January 2005 and December 2011. Through individual-level linkage of population-based medical databases, type 2 diabetes was identified using a previously validated algorithm including hospital diagnoses, filled prescriptions for anti-diabetic drugs, and elevated HbA1c levels. Metformin use was identified by filled prescriptions within 90 days before admission. Covariates included surgery, preadmission morbidity, diabetes duration, and concurrent drug use. We computed 30-day mortality and hazard ratios (HRs) of death using Cox regression adjusted for covariates, both overall and after propensity score matching. RESULTS: We included 7,404 adult type 2 diabetes patients, representing 14.0% of 52,964 adult patients admitted to the ICUs. Among type 2 diabetes patients, 1,073 (14.5%) filled a prescription for metformin as monotherapy within 90 days before admission and 1,335 (18.0%) received metformin in combination with other anti-diabetic drugs. Thirty-day mortality was 17.6% among metformin monotherapy users, 17.9% among metformin combination therapy users, and 25.0% among metformin non-users. The adjusted HRs were 0.80 (95% confidence interval (CI): 0.69, 0.94) for metformin monotherapy users and 0.83 (95% CI: 0.71, 0.95) for metformin combination therapy users, compared to non-users. Propensity-score-matched analyses yielded the same results. The association was evident across most subgroups of medical and surgical ICU patients, but most pronounced in elderly patients and in patients with well-controlled diabetes. Former metformin use was not associated with decreased mortality. CONCLUSIONS: Preadmission metformin use was associated with reduced 30-day mortality among medical and surgical intensive care patients with type 2 diabetes.