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All Studies   Meta Analysis    Recent:   
0 0.5 1 1.5 2+ Mortality, prediabeties 59% Improvement Relative Risk Severe case, prediabeties 54% Progression, prediabeties 42% Progression, prediabe.. (b) 37% Progression, PCOS 41% Progression, PCOS (b) 34% Metformin for COVID-19  Chan et al.  Prophylaxis Is prophylaxis with metformin beneficial for COVID-19? Retrospective 3,136 patients in the USA Lower severe cases (p=0.37) and progression (p=0.37), not sig. c19early.org Chan et al., medRxiv, August 2022 Favors metformin Favors control

Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes

Chan et al., medRxiv, doi:10.1101/2022.08.29.22279355
Aug 2022  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
 
*, now known with p < 0.00000000001 from 89 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19early.org
Retrospective 3,136 patients with prediabetes and 282 with PCOS, showing metformin associated with reduced COVID-19 severity.
risk of death, 58.6% lower, OR 0.41, p = 0.66, treatment 400, control 2,736, adjusted per study, mortality/hospice, multivariable, prediabeties, RR approximated with OR.
risk of severe case, 54.1% lower, OR 0.46, p = 0.37, treatment 400, control 2,736, adjusted per study, multivariable, prediabeties, RR approximated with OR.
risk of progression, 42.4% lower, RR 0.58, p = 0.37, treatment 51 of 400 (12.8%), control 798 of 2,736 (29.2%), NNT 6.1, adjusted per study, odds ratio converted to relative risk, moderate, multivariable, prediabeties.
risk of progression, 37.0% lower, OR 0.63, p = 0.37, treatment 400, control 2,736, adjusted per study, mild ER, multivariable, prediabeties, RR approximated with OR.
risk of progression, 40.7% lower, OR 0.59, p = 0.22, treatment 196, control 86, adjusted per study, moderate, multivariable, PCOS, RR approximated with OR.
risk of progression, 34.5% lower, OR 0.66, p = 0.20, treatment 196, control 86, adjusted per study, mild ER, multivariable, PCOS, RR approximated with OR.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Chan et al., 30 Aug 2022, retrospective, USA, preprint, 15 authors. Contact: justinreese@lbl.gov.
This PaperMetforminAll
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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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.</jats:p></jats:sec><jats:sec><jats:title>Participants</jats:title><jats:p>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.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>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 &lt; 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 &lt; ' '0.001). In patients with PCOS, we found no significant association between metformin use and ' 'COVID-19 severity, although the number of patients was relatively ' 'small.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Metformin was ' 'associated with less severe COVID-19 in patients with prediabetes, as seen in previous ' 'studies of patients with diabetes. This is an important finding, since prediabetes affects ' 'between 19 and 38% of the US population, and COVID-19 is an ongoing public health emergency. 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