Metformin Does Not Reduce Hospitalisation for COVID-19
Terry Cheuk-Fung Yip, Andrea On, Yan Luk, Chung-Yan Grace, MD Lui, BSc Mandy Sze-Man Lai, MD Wai-Sun Wong, MPhil Yee-Kit Tse, Henry Lik-Yuen, MD Chan, MD Shu-Cheong Hui, Alice Pik, MD Shan Kong, Lai-Hung Grace, MD Wong
Background A recent randomised trial demonstrated the lack of effect of metformin in preventing severe coronavirus disease 2019 (COVID-19) in non-hospitalised adults.
Methods This was a territory-wide retrospective cohort study in Hong Kong. Non-hospitalised adults with COVID-19 and diabetes who attended designated outpatient clinics during the peak of omicron outbreak were identified. Patients were classified into metformin users and non-users. The primary composite end point was hypoxemia, emergency department visit, hospitalisation, or death. Propensity score weighting analysis was adopted to balance the clinical characteristics of metformin users and non-users. Weighted Cox proportional hazard regression after propensity score weighting was performed.
Findings A total of 12,331 patients with diabetes (8,604 metformin users and 3,727 non-users) were included in the primary analysis. The mean age of the patients was 69 years; 50.6% were female, mean glycated hemoglobin was 7.1%, 43% had been vaccinated, and 28.0% had received molnupiravir or nirmatrelvir/ritonavir. The weighted hazard ratio for the primary end point at Day 30 was 0.85 (95% confidence interval [CI], 0.68 to 1.05; P=0.134) with metformin. In secondary analyses, the weighted hazard ratio for emergency department visit, hospitalisation, or death was 0.85 (95% CI, 0.68 to 1.07; P=0.163) with metformin. The weighted hazards ratio for hospitalisation or death was 0.93 (95% CI, 0.72 to 1.22; P=0.614) with metformin.
Interpretation Use of metformin is not associated with a reduced risk of hypoxemia, emergency department visit, hospitalisation, or death in patients who have diabetes and are not hospitalised for COVID-19 in the real world.
would be adjusted in the doubly robust model. The effective sample size after propensity score weighting was 8,604 and 1,264 in metformin users and nonusers respectively. † The definition of comorbidities was stated in Supplementary Table 2 . ‡ The number of patients with complete vaccination was estimated by the product of the number of patients and the complete vaccination rate in the general population matched with the age, sex, and baseline date. Abbreviations: ASMD = absolute standardized mean difference, DPP-4 inhibitors = dipeptidyl peptidase-4; GLP-1 = glucagon-like peptide-1; SGLT2= Sodium-glucose co-transporter 2; TZD = thiazolidinediones. This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4225660 P r e p r i n t n o t p e e r r e v i e w e d This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4225660 P r e p r i n t n o t p e e r r e v i e w e d This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=4225660 P r e p r i n t n o t p e e r r e v i e w e d
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