Metformin use is associated with a decrease in the risk of hospitalization and mortality in COVID ‐19 patients with diabetes: A population‐based study in Lombardy
Luisa Ojeda‐fernández, MSc Andreana Foresta, MSc Giulia Macaluso, MSc Pierluca Colacioppo, MSc Mauro Tettamanti, Antonella Zambon, MD Stefano Genovese, MSc Ida Fortino, MSc Olivia Leoni, MSc Maria Carla Roncaglioni, Marta Baviera
Diabetes, Obesity and Metabolism, doi:10.1111/dom.14648
Aims. We compared the association of metformin use and COVID-19 outcomes in a cohort of 31,966 patients with diabetes in Lombardy. Methods. We used a COVID-19 linkable administrative regional database to select diabetic patients over 40 years old. They had at least two prescriptions of antidiabetic drugs in 2019 and a positive test for SARS-CoV-2 between 15 February 2020 and 15 March 2021. The association of metformin use and clinical outcomes was assessed by multivariable logistic regression analyses and after propensity score matching. Clinical outcomes were all-cause mortality, in-hospital mortality, hospitalization for COVID-19 and admission to an intensive care unit (ICU). Results. In multivariable models metformin use was associated with a significantly lower risk of total mortality (OR 0.70; 95% CI 0.66-0.75), in-hospital mortality (OR 0.68; 95% CI 0.63-0.73), hospitalization for COVID-19 (OR 0.86; 95% CI 0.81-0.91) and ICU admission (OR 0.81; 95% CI 0.69-0.94) compared with metformin non-users. Results were similar in propensity score analysis; metformin was associated with significantly lower risk of total mortality (OR 0.79; 95% CI, 0.73-0.86), in-hospital mortality (OR 0.74; 95% CI, 0.67-0.81) and ICU admission (OR 0.77; 95% CI, 0.63-0.95).
Conclusions. In this large cohort, metformin use was associated with a protective effect in COVID-19 clinical outcomes, suggesting that it might be a potentially useful drug to prevent severe COVID-19 disease, although randomized clinical trials (RCT) are needed to confirm this. While awaiting the results of RCT, we suggest continuing prescribing metformin to diabetic patients with COVID-19.
part by confounding by indication, because metformin is used early in the trajectory of T2DM whereas insulin is typically started later. 28, 29 To minimize the effect of bias by indication, in a sensitivity analysis we excluded patients treated with insulin before and after PSM, substantially confirming result of the main analysis.
Conclusions 1. Our results show that metformin use is associated with a lower risk of total and in-hospital mortality and with a good prognosis in patients with diabetes and COVID-19 compared to metformin non-users. 2. Since metformin is an inexpensive and well-tolerated drug, it is suitable for investigating the effectiveness in COVID-19 patients in randomized clinical trials (RCT) to overcome the limits of observational studies. 3. While awaiting results from RCT, we suggest continuing prescribing this drug.
CONFLICT OF INTEREST All authors declare no conflict of interest
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