The University of Minnesota Medical School received funding from the Parsemus Foundation to start a study focusing on the widely-used diabetes medication known as metformin. The key question: can this economical and available drug be used to help fight COVID-19? A randomized, controlled study planned will help two co-principal investigators pursue what could be a materially breakthrough in the search for treatments targeting COVID-19. Although the recent grant support from the Parsemus Foundation is a healthy start, the University of Minnesota investigators need additional capital to complete the entire clinical trial.
An Important Goal: A Generic Low Cost Approach Targeting COVID-19
The CDC forecasts predict 1,300 to 5,500 new COVID-19 hospitalizations per day by Oct. 12 in the U.S. alone. This means that a treatment that reduces hospitalization by about 50-60%, as evidenced by observational data, could potentially prevent thousands of hospitalizations each day in the U.S.. With generics available for less than $4 per month from manufacturers around the globe, metformin also has the advantage that it can be used immediately and inexpensively worldwide. Metformin is also safe in everyone (children, pregnant women, adults of any age), as long as they don’t have significant kidney, liver or heart failure.
Funded by the Parsemus Foundation, this includes covering the costs of the investigational new drug application to the U.S. Food and Drug Administration (FDA) to launch a multi-center randomized controlled trial of the use of metformin as a COVID-19 treatment and prevention method. Led by co-principal investigators Carolyn Bramante, MD, MPH and Christopher Tignanelli, MD. The team submitted the IND application on August 12 and hope to secure additional funding over the next few weeks.
What’s the Basis for the Research?
As it turns out there is some epidemiological data indicating that metformin may in fact help slow down the rate of hospitalization associated with COVID-19 reports Dr. Bramante stating “And a mechanism of action is there—metformin has a little-known past as an antiviral, in addition to its blood sugar reduction and inflammation-reducing effects. TNFα and mTOR are among the proposed pathways. But a randomized clinical trial is needed to be sure the association is truly cause and effect.”
“Several observational studies in the U.S. and around the world have shown an association between outpatient metformin use and reduced mortality and hospitalizations for COVID-19,” Bramante said. “The most recent papers (one not yet publicly available), were done in detailed databases that allowed accounting for body mass index and degree of glucose in the body (hemoglobin A1C). There are known mechanisms of metformin that would reduce severity of COVID-19, including its inflammation reducing effects, and potentially also its ability to inhibit mTOR, a protein that helps the virus grow.”
Metformin, familiar to many by the brand names Fortamet or Glucophage, is used as a diabetes medication to lower glucose levels, with a common side benefit of reduced appetite and weight loss. Findings from previous studies provided Bramante’s team with a reason to believe that metformin is a promising treatment and prevention method for COVID-19, including preliminary data from an observational study co-led by Bramante and Tignanelli. The team examined de-identified data from UnitedHealthcare and found that women already taking metformin who were diagnosed with COVID-19 had about 25% reduced risk of mortality. Preliminary data from another observational study of patients with non-alcoholic fatty liver disease, co-led by Bramante and Tignanelli, showed that treatment for metabolic disease, including taking metformin, was associated with a lower likelihood of being hospitalized due to COVID-19. The findings align with results from observational studies in China and France and from the University of Alabama.
Upon approval of the IND application, the goal of the clinical trial will be two-fold: to definitively study whether or not metformin prevents SARS-CoV-2 infection and whether or not it can prevent severe COVID-19 disease and hospitalization in those who are infected. The unique study they have designed will also elucidate what duration of metformin is needed to achieve those benefits. Since metformin is already widely used and available, its use to fight COVID-19 could begin as soon as there are positive clinical results and would change the global standard of care for prevention and early-stage disease, similar to recent definitive results on dexamethasone for advanced disease.
Carolyn Bramante, MD, MPH, Department of Medicine
Christopher Tignanelli, MD, Department of Surgery
Call to Action: The University of Minnesota researchers are searching for additional funding. Although the Parsemus Foundation has provided initial funding, it’s not enough to fund the entire clincial trial. Contact the co-principal investigators to connect.