Early outpatient treatment of COVID-19 with metformin could reduce the risk of developing long COVID

By Dr. Chinta SidharthanReviewed by Aimee MolineuxMar 9 2023

In a recent study posted to Preprints with The Lancet*, a team of researchers from the United States investigated whether early outpatient treatment of coronavirus disease 2019 (COVID-19) patients with fluvoxamine, ivermectin, or metformin could prevent long coronavirus disease (long COVID).

*Important notice: Preprints with The Lancet / SSRN publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background

Long COVID or post-acute sequelae of  COVID-19 (PASC) comprises a wide range of symptoms that persist for months after the individual has recovered from the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Symptoms include headaches, fever, debilitating fatigue, post-exertional malaise, dyspnea, loss of taste or smell, and more serious symptoms that affect organ symptoms such as cardiovascular complications, cognitive and neurological impairments, and renal and gastrointestinal problems.

Estimates by the Centers for Disease Control and Prevention (CDC) indicate that long COVID is disproportionately prevalent among populations of racial or ethnic minorities. Furthermore, at least 15% of the adults in the U.S. develop long COVID-like symptoms after recovering from the SARS-CoV-2 infection. Therefore, it is essential to understand the factors determining the incidence of long COVID and find COVID-19 therapies that can potentially prevent the development of PASC.

About the study

In the present study, the researchers conducted a large-scale, quadruple-blinded, randomized, placebo-controlled, phase three clinical trial that assessed the efficacy of early outpatient treatment of COVID-19 patients with fluvoxamine, ivermectin, or metformin. They conducted a 300-day follow-up to determine if the early treatment preventet PASC.

The participants consisted of overweight or obese adults between the ages of 30 and 85 who had laboratory-confirmed SARS-CoV-2 infection within the previous week and had no other history of COVID-19. Regular medication with any one of the three medications being studied or an emergency use authorized treatment with any one of the three medications resulted in the exclusion of the participant, but COVID-19 vaccination was not an exclusion criterion. While pregnant or lactating women were included in the study, the treatment consisted only of metformin or a placebo. Neither of the other two medications was used since there was insufficient information on the safety of fluvoxamine and ivermectin use in pregnant or lactating women.

Varying doses and regimens of the three medications were tested against a placebo through a randomized study design. The participants were actively followed-up for four weeks, post which surveys were used to follow up every month for 300 days. The measured outcomes included a long COVID diagnosis from a medical practitioner that the participant reported. A time-to-event approach was used to analyze these diagnoses.

Results

The findings indicated that early outpatient treatment of COVID-19 patients with metformin resulted in a relative decrease of 42% and an absolute decrease of 4.3% in the incidence of long COVID, compared to a placebo, and reduced the long COVID hazard ratio to 0.58. Treatment with ivermectin and fluvoxamine did not show similar results. Among the group treated with metformin, the incidence rate of long COVID was 6.3% as compared to the placebo group, which reported a 10.6% long COVID incidence rate. Furthermore, metformin treatment was also seen to reduce the incidence of severe COVID-19-related hospitalization, emergency department visits, and mortality by 40%.

The cumulative long COVID incidence among the group treated with ivermectin was 8%, as compared to those treated with the placebo, who had a long COVID incidence rate of 7.5%, indicating that ivermectin did not have any long COVID preventative benefits. Similarly, the fluvoxamine treatment group had a long COVID incidence rate of 10.1%, as compared to the placebo group, which had an incidence rate of 7.5%.

The study also reported that female participants had a higher incidence (11.1%) of long COVID diagnoses than male participants (4.9%). Still, a minimum of one primary COVID-19 vaccination reduced the risk of developing long COVID significantly compared to unvaccinated individuals. Only one out of the 57 boosted participants developed long COVID, emphasizing the importance of primary and booster doses of COVID-19 vaccines in reducing the risk of long COVID.

Conclusions

Overall, the findings indicated that early treatment of COVID-19 patients with metformin not only reduced the risk of hospitalization and mortality by 40% but also decreased the probability of developing long COVID symptoms after recovering from the SARS-CoV-2 infection. Treatment with ivermectin or fluvoxamine, however, did not show similar success in preventing long COVID development.

*Important notice: Preprints with The Lancet / SSRN publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.