A new clinical study comparing several outpatient drug therapies has revealed a “major finding” that could decrease new cases of Long COVID. Here, MedPage Today editor-in-chief Jeremy Faust, M.D., explains the trial results and what they mean for patients.*

The COVID-OUT Study

Since August 2020, a team of U.S. investigators led by the University of Minnesota has been engaged in the COVID-OUT Study or Early Outpatient Treatment for SARS-CoV-2 Infection (COVID-19). The study was a multi-center Phase 3 clinical trial testing the effectiveness of several generic therapies for outpatient treatment of COVID-19. These included:

• Metformin, a diabetes drug used to help control blood sugar
• Fluvoxamine, an obsessive-compulsive disorder treatment
• Ivermectin, a drug used for treating parasitic roundworm infection

Each drug was compared to a placebo, both individually and in combination (i.e., metformin+fluvoxamine and metformin+ivermectin). 

The aim was to see whether these drugs could mitigate COVID-19 and prevent Long COVID.

What the researchers did

Patients were enrolled in the study right after the receipt of a COVID-19 diagnosis or the appearance of symptoms. 

As described by Faust, and documented in a paper called “Outpatient Treatment of COVID-19 and the Development of Long COVID Over 10 Months”:

• The randomized controlled trial involved more than 1,000 participants over nine months of follow-up.
• Participants randomly received metformin, fluvoxamine, ivermectin, or a placebo in a 1:1:1:1 fashion, generally within several days of disease onset.
• The median age of participants was 45 years (half were aged 37-54 years), most were female, and many were overweight.

What they found

The team’s principle finding was highly significant: people taking metformin experienced a cumulative incidence (new case(s)) of Long COVID of 6.3% versus 10.6% in those who took a placebo.  

“That’s a massive, massive finding in a disease like this,” states Faust. “We do know that metformin made a huge difference.” The difference became more pronounced as time progressed, peaking by day 300 before stabilizing—”a really important sign that this was a real effect that was measured.”

Further, metformin was found to perform better in:

• Women,
• Younger people,
• People with a body mass index over 30, and
• People who received the drug less than four days after diagnosis.

There was no significant difference between the fluvoxamine, ivermectin, and placebo groups.

Vaccinated people were also found to be about 50% less likely to develop Long COVID.

What it means

“We now have a way to possibly decrease Long COVID,” says Faust. “I think what is so key here is that this study showed that Long COVID is a modifiable disease, and that actually is profound. If a disease is not treatable or too amorphous to be even understood well enough to treat, we can’t see a separation in a randomized controlled trial.”

To Faust, the trial shows not just that metformin lowers Long COVID risk but that we understand the disease enough to measure and modify it. “That to me is actually a major, major finding.”

*Hutto, E. (2023, March 21). Finally, a Potential Therapy to Prevent Long COVID [Video file]. MedPage Today. Retrieved from https://www.medpagetoday.com/infectiousdisease/longcovid/103628