COVID-19 and Metformin

Bottles of Metformin on a shelf

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Metformin for COVID-19 treatment

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? Can medications like metformin effectively treat COVID-19?

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). 

Controlled clinical trials

The Together Trial was a randomized, controlled clinical trial conducted in Brazil that  reported on the use of metformin and other medications for treatment of COVID-19. Of 1497 participants, 327 individuals were provided metformin. The study did not find that metformin reduced hospitalizations or emergency room visits.

The COVID-OUT double-blind, controlled, randomized clinical trial evaluated the impact of metformin, fluvoxamine, ivermectin, and combinations as treatment for 1323 newly diagnosed COVID participants. Metformin lowered the odds of emergency department visits, hospitalizations, or death. However, fluvoxamine and ivermectin did not have a significant effect.

A drug derived from metformin (called metformin glycinate) has recently been shown to reduce the COVID viral load in cell cultures by 98%, and was reduced the virus and the need for supplemental oxygen in a small clinical trial of COVID-infected individuals.

Metformin has not been approved by the U.S. FDA for emergency use for COVID-19 treatment.

Metformin molecule

COVID-19 and Metformin

  • 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)
  • Bramante CT, Huling JD, Tignanelli, CJ, et al. (2022). Randomized trial of metformin, ivermectin, and fluvoxamine for Covid-19. N Engl J Med 2022; 387:599-610. (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).
  • 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).
  • 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)
  • 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)
  • Ventura-Lopez C, Cervantez-Luevano K, Aguirre-Sanchez JS, et al. (2022). Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial. Biomed Pharmacother 152: 113223. (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)

Human Health News

We’re sorry, you are not eligible for the nationwide COVID-OUT or ACTIV-6 studies, but you may be eligible for other federal trials:

And if you don’t find a match there, this slightly more complex clinical trials finder includes studies sponsored by companies as well:

Trials Today