Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes
Lauren E Chan, Elena Casiraghi, Bryan Laraway, Ben Coleman, Hannah Blau, Adnin Zaman, Nomi Harris, Kenneth Wilkins, Michael Gargano, Giorgio Valentini, David Sahner, Melissa Haendel, Peter N Robinson, Carolyn Bramante, Justin Reese
doi:10.1101/2022.08.29.22279355
Background: With the continuing COVID-19 pandemic, identifying medications that improve COVID-19 outcomes is crucial. Studies suggest that use of metformin, an oral antihyperglycemic, is associated with reduced COVID-19 severity in individuals with diabetes compared to other antihyperglycemic medications. Some patients without diabetes, including those with polycystic ovary syndrome (PCOS) and prediabetes, are prescribed metformin for off-label use, which provides an opportunity to further investigate the effect of metformin on COVID-19.
Participants: In this observational, retrospective analysis, we leveraged the harmonized electronic health record data from 53 hospitals to construct cohorts of COVID-19 positive, metformin users without diabetes and propensity-weighted control users of levothyroxine (a medication for hypothyroidism that is not known to affect COVID-19 outcome) who had either PCOS (n = 282) or prediabetes (n = 3136). The primary outcome of interest was COVID-19 severity, which was classified as: mild, mild ED (emergency department), moderate, severe, or mortality/hospice.
Results: In the prediabetes cohort, metformin use was associated with a lower rate of COVID-19 with severity of mild ED or worse (OR: 0.630, 95% CI 0.450 -0.882, p < 0.05) and a lower rate of COVID-19 with severity of moderate or worse (OR: 0.490, 95% CI 0.336 -0.715, p < 0.001). In for use under a CC0 license.
Conflict of Interest The authors declare no conflicts of interest. Supplementary Figure S2 . Forest plots for the prediabetes cohort. A: Mild, mild ED, and moderate vs severe and worse, B: Mild, mild ED, moderate, and severe vs death with COVID-19 Supplementary Figure S3 . Forest Plots for univariate odds ratios computed to assess the non-collapsibility effect for chronic respiratory disease. According to Schuster et al., 50 noncollapsibility effects on a covariate can be estimated by comparing the OR obtained by univariate LR on the variable and the OR obtained in the multivariate analysis. To check whether the OR for chronic-respiratory disease is affected by the non-collapsibility effect we therefore run an univariate LR for each outcome. The forest plot reports the results obtained when univariate LRs were applied to either drug usage ("on metformin") or chronic respiratory disease; the ORs for drug usage are comparable to those obtained by multivariate LR (Fig. 4a, 4b ) showing the reliability of the estimate. On the other hand, the remarkable difference in the ORs estimated for chronic respiratory disease confirm the non-collapsibility effect for this variable. e , for use under a CC0 license.
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