Metformin is a widely used medication in treating Type II diabetes. It is also somewhat of a “wonder” drug, treating a range of diseases, including some forms of cancer, obesity, cardiovascular disease, and “aging.”
While its primary action is reducing blood sugar, metformin has some antiviral activity against Zika and Hepatitis C and some anti-inflammatory actions. It has an excellent safety profile. [1] As a result, the researchers included metformin along with ivermectin, fluvoxamine (a selective serotonin reuptake inhibitor used in treating obsessive-compulsive disorders), and a placebo in a randomized clinical trial of outpatient treatment of severe COVID-19.
The trial, COVID-OUT, sought to determine whether metformin prevented “severe” COVID. Severity was defined as one of 4 clinical parameters.
- A reading < 94% SpO2, your oxygen saturation, on an oximeter
- Emergency Department Visit
- Hospitalization
- Death
We have learned, as the researchers report, ”that 1 reading below 94% is not severe COVID-19,” and the criteria dropped. The study found that metformin reduced the odds of the composite of the three parameters of severe COVID-19 by 42% by day 14, hospitalization and death by 58% on day 28, and long COVID by 42% on day 300. [2] Having demonstrated a significant clinical response to metformin in reducing the severity of COVID-19, the researchers in this current study looked at the changes in viral load. As a reminder, viral load is a measure that reflects both the severity of COVID-19 and its ability to infect others.
The participants were of “standard-risk,” 30 to 85, overweight or obese, with no prior COVID-19 infection, and documented COVID-19 within three days of enrollment. Similar numbers of participants in the placebo and metformin groups had been vaccinated, and the study's time frame included the alpha, delta, and Omicron variants. 999 individuals in the COVID-OUT research participated in this substudy self-collecting nasal swabs on Days 1, 5, and 10 of treatment.
- Statistically, metformin significantly reduced COVID-19 viral loads over 10 days. This was also clinically impactful, reducing the outcomes of severe COVID-19 by 55% and Long COVID by 65%
- The effect was more significant when used earlier in the course of the disease when symptoms had been present for less than four days, “consistent with an antiviral action.”
- Viral rebound, higher viral loads on Day 10 compared to Day 5 were less, 68% in the metformin group, 3.28% vs. 5.95% in the placebo arm.
- There was an additional increase in metformin’s efficacy in those vaccinated, posited by the researchers as the priming of immunologic memory.
- “Neither ivermectin nor fluvoxamine had virologic effect.”
The sharp-eyed will notice the deflection of the downward trends on day 5. The researchers ascribed this to the dose titration protocol for metformin. Metformin, when used in treating diabetes, is prescribed at a daily set dose. In this study, participants were given the standard 500mg dose on Day 1, 1000mg from Day 2 to 5, and 1500 mg for days 6 to 14. The step dose was used to mitigate metformin’s dose-dependent adverse impact on the GI tract.
COVID-19 has not revealed its secrets or how we might best treat it. This study suggests that metformin's unexpected role in curbing the severity of the virus, coupled with its ability to reduce viral loads, favorable safety profile, and cost-effectiveness compared to alternative treatments like Paxlovid, is a compelling addition to the arsenal against infectious diseases.
[1] “Metformin is safe in children and pregnant individuals with and without preexisting diabetes and does not require checking blood sugar levels. It does not increase the risk of lactic acidosis found in other drugs in metformin’s chemical class.
[2] Neither ivermectin nor fluvoxamine demonstrated any benefit.
[3] While not compared head-to-head, metformin was less effective in reducing viral loads than the data on Paxlovid.
Source: Favorable Antiviral Effect of Metformin on Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of Coronavirus Disease 2019 Clinical Infectious Disease DOI:10.1093/cid/ciae159
Chuck Dinerstein, MD, MBA
Director of Medicine
Dr. Charles Dinerstein, M.D., MBA, FACS is Director of Medicine at the American Council on Science and Health. He has over 25 years of experience as a vascular surgeon.
