COVID-OUT Clinical Trial Results Announced
- Metformin, an inexpensive diabetes medication, proved superior to other existing medications in treating COVID-19 infection.
- Metformin reduced serious outcomes for COVID-19 by 42% and over 50% when treated within 4 days of symptoms.
- Neither ivermectin nor a low dose of fluvoxamine improved COVID outcomes.
- More information on the COVID-OUT and Media Resources pages
Project Topics
Metformin for COVID
Individuals with diabetes are at higher risk of severe illness from COVID-19 infection. Can tighter control over blood glucose levels make a difference to patients?
A publication by an Italian team provided evidence that COVID-19 patients with hyperglycemia who were treated with insulin infusion had a lower risk of severe disease than patients without insulin infusion. And scientists in China, France, and the U.S. reported that patients with the virus and pre-existing Type 2 diabetes had better outcomes if they had improved glycemic control or were on diabetes medication (metformin), and worse outcomes with uncontrolled hyperglycemia.
Observational studies have suggested a possible benefit of treatment with metformin, a common medication for people with type II diabetes or prediabetes, for COVID-19 outcomes. Scientists have called for more clinical research on metformin and its ability to treat COVID-19 infection. This inexpensive (<$5/month) medication may have antiviral action. Metformin has been used for years off-label to treat other metabolic conditions like obesity, cardiovascular disease, and high blood pressure — the same risk factors for poor outcomes after COVID-19 infection. Metformin is also safe to use during pregnancy.
Metformin lowers blood sugar and inflammation by activating an enzyme called AMPK. This activity also appears to reduce angiotensin-converting enzyme 2 (or ACE2), which serves as a gateway for COVID-19 to enter and infect cells. Thus, the way metformin works to control blood sugar might also help to control coronavirus infection (see Everyday Health and UC San Diego Health).
Randomized controlled studies will determine if the survival benefits observed are due to metformin or some other factors. The Together Trial did not find that metformin reduced hospitalizations, but the University of Minnesota COVID-OUT clinical trial evaluating metformin will provide more information.
Additional Resources
Metformin
- Usman A, Bliden KP, Cho A, et al. (2022). Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes. J Thromb Thrombolysis. Jan 18 : 1–9. (free full text)
- Reis G, Silva EAM, Silva DCM, et al. Effect of early treatment with metformin on risk of emergency care and hospitalization among patients with COVID-19: The TOGETHER randomized platform clinical trial. Lancet Reg Health Am Feb; 6: 100142. (free full text).
- Ojeda-Fernández L, Foresta A, Macaluso G, et al. (2022). Metformin use is associated with a decrease in the risk of hospitalization and mortality in COVID-19 patients with diabetes: A population-based study in Lombardy. Diabetes Obes Metab. 1–8 (free full text).
- Bramante C, Ingraham N, Murray T, et al. (2021). Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis Lancet Healthy Long 2(1):e34–41. (free full text)
- Ibrahim S, Lowe JR, Bramante CT, et al. (2021). Metformin and Covid-19: Focused review of mechanisms and current literature suggesting benefit. Front. Endocrinol. 12:587801. (free full text).
- Bode B, Garrett V, Messler J, et al. (2020). Glycemic characteristics and clinical outcomes of COVID-19 patients hospitalized in the United States. J Diabetes Sci Technol 14(4):813-821. (free full text)
- Sardu C, D’Onofrio N, Balestrieri ML, et al. (2020). Outcomes in patients with hyperglycemia affected by Covid-19: Can we do more on glycemic control? Diabetes Care 43(7): 1408–1415. (free full text)
- Zhu L, She Z, Cheng X, et al. (2020). Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing Type 2 diabetes. Cell Metabolism 31, 1068–1077. (free full text)
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