SAN DIEGO — Scripps Research in La Jolla announced a new clinical trial Thursday that will assess the effectiveness of using drugs approved for diabetes treatment and weight loss to treat long COVID-19, the debilitating chronic condition diagnosed in an estimated 20 million Americans and about 400 million people worldwide.

Developed to help people with type 2 diabetes control their blood sugar levels, these GLP-1 medications have generated billions of dollars in revenue for their ability to slow the pace of digestion and reduce appetite, helping millions worldwide lose weight.

But, as always happens with big pharma blockbusters, the research community is busy exploring other possible applications for this class of compounds, with clinical trials underway or forming in cardiovascular disease, chronic kidney disease and obstructive sleep apnea.

And growing evidence of its anti-inflammation properties, notes Scripps computational biologist and study co-principal investigator Julia Vogel, has driven increasing interest in using GLP-1 drugs to treat at least some of long COVID’s myriad symptoms, which range from brain fog and difficulty breathing to fatigue and joint pain.

The trial, which seeks to enroll 1,000 long COVID patients nationwide, will explore how self-administration of tirzepatide, Eli Lilly’s GLP-1 agonist marketed as Mounjaro for diabetes treatment and Zepbound for weight loss, affects symptoms over a 12-month period.

“GLP-1 drugs have been found to do so many different things,” Vogel said. “They’ve helped with all kinds of immune conditions, in part by reducing inflammation, and we know that is an issue in long COVID.”

Desperate for therapies that work, the long COVID community has already begun experimenting with “microdosing” GLP-1 drugs, with a post made one year ago on the social news site Reddit titled “Ozempic for Long Covid?” reporting anecdotal evidence of the drug helping some improve their symptoms. And the formal scientific community has taken note, with a formal discussion of GLP-1’s possibilities for long COVID occurring during a panel discussion at a scientific meeting on Sept. 12 and still available on YouTube.

“We’ve heard anecdotal reports of people who literally, on their first shot, just feel like their symptoms are just clearing like they didn’t even realize that they had so much anxiety until it was just gone,” Vogel said.

Given that there is currently no drug to treat long COVID despite more than $1 billion in spending on research by the federal government, the possibility that GLP-1 drugs are beneficial in this domain is extremely appealing. However, anecdotal evidence will never convince health insurance companies to cover such prescriptions, nor doctors to broadly write prescriptions without proof of efficacy. Those are the goals of the new Scripps Research study.

Dr. Eric Topol, the study’s co-principal investigator and a well-known Scripps vice president, noted that no trials to date, and there have been very few so far, have met the level of rigor that will be employed for the Long COVID Treatment Trial.

“There has still not been a large, randomized, placebo-controlled trial of a candidate drug,” Topol said. “That is what we have started this week with tirzepatide.”

Trial protocols call for half of the 1,000 participants to receive a placebo, inert doses that have no effect, rather than the active drug, creating a control group that is critical to obtaining scientifically valid results.

Scripps Research, he noted, has written many papers on long COVID since the pandemic. A paper that a team of researchers published in January 2023 titled “Long COVID: major findings, mechanisms and recommendations” that details how this lingering illness affects many different systems of the body has been particularly well received, with nearly 2 million views.

Vogel herself suffers long COVID fatigue so severe that the former distance runner was forced to begin using a wheelchair and leave San Diego, rejoining her extended family on the East Coast. It was seeing one of their own so severely affected by the condition, Topol said, that spurred a strong dedication to long COVID research.

“Julia was hit in early 2020, and her suffering and course led to our work to learn about the condition and seek a treatment,” Topol said in an email Thursday.

GLP-1 drugs, including Ozempic and Wegovy from Novo Nordisk, are designed to be self-administered, with patients giving themselves shots once per week. This fact allowed the Scripps team to create a “digital” trial that mails supplies to participants rather than requiring them to travel to clinical sites as many trials do.

Participants, who must have medical documentation of long COVID, will receive four doses of tirzepatide in the mail, starting with lower concentrations of the active ingredient and increasing over six months to find each participant’s “optimal dose,” Vogel said.

“We ask them to report their weight and any side effects every week and then each month, before their next shipment, there’s a discussion with one of the study physicians about, ‘OK, are you still having any side effects?’” Vogel said. “If they’re still having any side effects, (the dose) does not go up.

“If they’re feeling better and they’re interested in going up, then they can, or they can just choose to stay where they are.”

Participants must regularly record their fatigue level using a special smartphone application so that researchers can understand how the drug affects this key measurement.

“We’re also going to be sending everyone a wearable (electronic monitor) so they will have this passive monitoring of their daily step count, their heart rate, heart rate variability, sleep, etc.,” Vogel said.

Fifty participants will be asked to go one step further, using a special device that can collect blood samples from the upper arm with the press of a button. These collections will allow deeper analysis of biomarkers and other factors that can be correlated with self-reported fatigue assessments and wearable data to provide a fuller picture of the biological effects of the drug.

In addition to a long COVID diagnosis, participants must be at least 18 years of age with internet access, a “fatigue severity scale score” of at least 36 and be willing to follow study protocols. Pregnant women are excluded because of the unknown potential risks of the drug to unborn babies. Those already taking tirzepatide, or any other GLP-1 drug, are also excluded, according to protocols posted on clinicaltrials.gov, as are those with certain medical conditions or medical histories that researchers have determined could confound results. Participants must also not be in the “underweight” category with a body mass index less than 18.5.

As co-principal investigator, Vogel is also barred from participating.

Is this bittersweet, given all that she has been through since she first started experiencing life-altering symptoms?

“I would not meet the eligibility criteria because I’m underweight, so I don’t mind at all,” Vogel said in an email Thursday. “My main feeling today is excitement about the potential to help people who are coping with the same illness that I am.

“Even if the drug does not decrease the symptom burden as we hope, we will learn a lot about its effects on people with Long COVID, and if it does help, I’ll be beyond thrilled.”

Lilly contributed the doses to the trial, which is funded by the Schmidt Initiative for Long Covid, a nonprofit organization created in 2023 by philanthropists Eric and Wendy Schmidt.

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