Metformin Does Not Reduce Hospitalisation for COVID-19

Abstract

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.

Funding Information: None.

Declaration of Interests: Terry Yip has served as an advisory committee member and a speaker for Gilead Sciences. Andrea Luk has served as a member of advisory panel for Amgen, AstraZeneca, Boehringer Ingelheim and Sanofi and received research support from Amgen, Asia Diabetes Foundation, Bayer, Boehringer Ingelheim, Lee’s Pharmaceutical, MSD, Novo Nordisk, Roche, Sanofi, Sugardown Ltd, Takeda. Grace Lui has served as an advisory committee member for Gilead, Merck, and GSK, speaker for Merck, Pfizer, and Gilead, and received research grant from Gilead, Merck, and GSK. Vincent Wong has served as a consultant or advisory committee member for AbbVie, Boehringer Ingelheim, Echosens, Gilead Sciences, Intercept, Inventiva, Merck, Novo Nordisk, Pfizer, ProSciento, Sagimet Biosciences, and TARGET PharmaSolutions; and a speaker for Abbott, AbbVie, Echosens, Gilead Sciences, and Novo Nordisk. He has received a research grant from Gilead Sciences, and is a cofounder of Illuminatio Medical Technology Limited. Henry Chan has served as an Independent Non-Executive Director for Shanghai Henlius Biotech Inc; as an advisory board member for Aligos, Aptorum, Arbutus, Hepion, Janssen, Gilead, Glaxo-Smith-Kline, Roche, Vaccitech, Virion Therapeutics, and Vir Biotechnology; and as a speaker for Gilead, Roche, and Viatris. Alice Kong has received research grants and/or speaker honoraria from Abbott, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli-Lilly, Kyowa Kirin, Merck Serono, Nestle, Novo Nordisk, Pfizer and Sanofi. Grace Wong has served as an advisory committee member for Gilead Sciences and Janssen, and as a speaker for Abbott, Abbvie, Ascletis, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen, and Roche. She has also received a research grant from Gilead Sciences. The other authors declare that they have no competing interests.

Ethics Approval Statement: The study protocol was approved by the Joint Chinese University of Hong Kong - New Territories East Cluster Clinical Research Ethics Committee (Reference number: 2021·239). Data were retrieved on 31 July 2022. Baseline date was defined as the date of the first appointment at designated clinic.

Keywords: Death, diabetes, hospital admission, hypoxaemia, metformin, SARS-CoV-2.