Abstract: Citation: Clin. Transl. Sci (2020) 13, 1055–1059; doi:10.1111/cts.12897 BRIEF REPORT Risk of Metformin in Patients With Type 2 Diabetes With COVID-19: A Preliminary Retrospective Report Yongchao Gao1,2,3,4, Tao Liu5, Weijun Zhong1,2,3,4, Rong Liu1,2,3,4, Honghao Zhou1,2,3,4, Weihua Huang1,2,3,4,* and Wei Zhang1,2,3,4,* The current outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread across the world. No specific antiviral agents have been adequately evidenced for the treatment of coronavirus disease 2019 (COVID19). Although metformin has been recommended as a host-directed therapy for COVID-19, there are some opposite views. The effects of metformin on the disease severity of patients with COVID-19 with diabetes during hospitalization remains unclear. This study aimed to determine the effect of metformin on disease severity. We enrolled 110 hospitalized patients with COVID-19 with diabetes prescribed either metformin or non-metformin hypoglycemic treatment for a case-control study. The primary outcome was the occurrence of life-threatening complications. There were no differences between the two groups in age, sex, comorbidities, and clinical severity at admission. Blood glucose and lactate dehydrogenase levels of the metformin group were higher than those of the non-metformin group at admission. Other laboratory parameters at admission and treatments after admission were not different between the two groups. Strikingly, the percentage of patients who experienced life-threatening complications was significantly higher in the metformin group (28.6% (16/56) vs. 7.4% (4/54), P = 0.004). Antidiabetic therapy with metformin was associated with a higher risk of disease progression in patients with COVID-19 with diabetes during hospitalization (adjusted odds ratio = 3.964, 95% confidence interval 1.034–15.194, P = 0.045). This retrospective analysis suggested a potential safety signal for metformin, the use of which was associated with a higher risk of severe COVID-19. We propose that metformin withdrawal in patients with COVID-19 be considered to prevent disease progression. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? ✔ Diabetes is one of the most important comorbidities of coronavirus disease 2019 (COVID-19) associated with higher mortality. Metformin has been proposed to be a candidate for host-directed treatment for COVID-19. However, recent studies have argued that the risks of metformin in patients with COVID-19 and diabetes need to be considered. WHAT QUESTION DID THIS STUDY ADDRESS? ✔ We aimed to assess the association between metformin and life-threatening complications by conducting a comparison on patients with COVID-19 with diabetes between metformin users and nonusers. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? ✔ Among those patients with COVID-19 with diabetes, more severe cases were found in metformin users than in non-metformin cases (28.6% vs. 7.4%, P = 0.004). Antidiabetic therapy with metformin was associated with a higher risk of severe illness (adjusted odds ratio 3.964, 95% confidence interval 1.034–15.194). HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? ✔ This study highlighted a potential safety signal for metformin, the use of which was associated with a higher risk of severe COVID-19. Thus, we propose that metformin withdrawal in patients with COVID-19 be considered to prevent disease progression. The current outbreak of..