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GLP-1 agonists

From MEpedia, a crowd-sourced encyclopedia of ME and CFS science and history

GLP-1 agonists (glucagon-like peptide-1 receptor agonists) are a class of drugs that includes semaglutide (Ozempic, Wegovy, Rybelsus), tirzepatide (Mounjaro, Zepbound), liraglutide (Victoza, Saxenda), and dulaglutide (Trulicity). Tirzepatide acts on both the GIP and GLP-1 receptors. The drugs are approved for type 2 diabetes and obesity. In 2023 and 2024, patients began to report on Reddit, Facebook, and other forums that GLP-1 agonists relieved their Long COVID or ME symptoms, and many patients now use them off-label.[1]

Theory

Patients and researchers suggest that GLP-1 agonists help through their anti-inflammatory effects, in particular on neuroinflammation.[2] Some reports say that the dual GIP/GLP-1 action of tirzepatide gives stronger anti-inflammatory effects than semaglutide.[1]

Evidence

No completed clinical trials have tested GLP-1 agonists in Long COVID or ME.

LC/ME Data patient survey (2026)

In April 2026, LC/ME Data published a survey of 120 people with Long COVID and/or ME who had tried a GLP-1 agonist.[1] The main findings were:

  • 53% improved, 20% had no change, and 28% worsened. 36% said they were "much improved" or better. Some who worsened reported a permanent drop in baseline, even after they stopped the drug.
  • The symptoms that improved most often were brain fog (44%), fatigue (37%), exercise tolerance (27%), post-exertional malaise (22%), and inflammation (21%).
  • Most people who improved noticed it within 1 to 2 weeks of starting or of a dose increase. A third noticed it on the same day. People who felt nothing by 4 to 6 weeks almost all ended up as non-responders.
  • Tirzepatide and semaglutide had similar overall improvement rates (54% and 50%). Tirzepatide gave more "very much improved" outcomes (14% against 5%), but the semaglutide group was small (n=20).
  • Patients with POTS or dysautonomia had the lowest improvement rate (46%) and 32% worsened. Patients with MCAS or GI symptoms had a 60% improvement rate.
  • Severe patients did worst: 35% improved and 40% worsened, against 58% and 26% for mild patients.
  • Patients ill for 6 years or more did best (67% improved, 14% worsened). Patients ill for 2 to 4 years did worst (38% worsened).
  • None of the 12 respondents with ME that was not linked to COVID reported "much worse" or "very much worse" outcomes, against 18% of Long COVID respondents.
  • The survey found no clear optimal dose. Some patients did best at 0.25 mg and others at 7.5 mg or higher.

The survey authors note that the sample was self-selected, retrospective, and had no control group. None of the subgroup differences were statistically significant. The anonymized dataset is publicly available.[1]

LoCITT-T trial (Scripps Research)

The Long COVID Treatment Trial-Tirzepatide (LoCITT-T, NCT07128082) is a randomized, double-blind, placebo-controlled trial of tirzepatide in Long COVID. Eric Topol and Julia Moore Vogel of Scripps Research lead it. The Schmidt Initiative for Long Covid funds it, and Eli Lilly supplies the drug. The trial was announced on 30 October 2025.[3][2]

  • Up to 1,000 adults in the US take part for up to 12 months. The trial is fully remote, with an interim safety and efficacy review at 3 months.
  • Participants start at 2.5 mg tirzepatide weekly and increase the dose monthly as tolerated.
  • The main outcome is fatigue, measured with the Fatigue Severity Scale. Other outcomes include cognition, post-exertional malaise, MCAS symptoms, and autonomic symptoms.
  • Participants need a Long COVID diagnosis. People with ME whose fatigue started before a COVID-19 infection cannot join.
  • Enrollment closed in December 2025. Scripps expects results about 14 months after recruitment is complete.[2]

Risks and safety

In the LC/ME Data survey, the most common side effects were nausea (30%), constipation (20%), post-dose fatigue (19%), insomnia (16%), diarrhea (13%), appetite suppression (10%), and heartburn or reflux (10%). Most GI side effects stopped within the first few weeks or after a dose reduction. Several patients who later worsened first reported insomnia. Rare serious events were gallstones (2 patients), suicidal ideation (1 patient, at 5 mg tirzepatide, which stopped when the drug was stopped), and sensorineural hearing loss (1 patient).[1]

Costs and availability

GLP-1 agonists are not approved for Long COVID or ME. They are prescription-only injections, except oral semaglutide (Rybelsus).

Notable studies

Articles and blogs

See also

Learn more

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 "GLP-1s for Long COVID and ME: Treatment Experience Survey Results". LC/ME Data. April 2026. Retrieved September 26, 2026.
  2. ↑ 2.0 2.1 2.2 "LoCITT-T - Long COVID Treatment Trial". Scripps Research. Retrieved September 26, 2026.
  3. ↑ "Scripps Research scientists launch new digital clinical trial to test repurposed drug for long COVID symptom relief". Schmidt Initiative for Long Covid. October 30, 2025. Retrieved September 26, 2026.
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