Treatment Database

Semaglutide (a GLP-1 receptor agonist) and tirzepatide (a dual GLP-1 and GIP receptor agonist), approved for type 2 diabetes and weight management, are being explored for Long COVID, MCAS and POTS. The main published human evidence is a 2025 case series of 47 people with MCAS (Afrin et al., American Journal of the Medical Sciences), in which 89% showed clinical benefit across a range of MCAS problems; it had no control group. For Long COVID, a clinician survey of patients who tried tirzepatide reported improvement in 60–90%, but its size and methods have not been published. To test this, Scripps Research launched LoCITT-T (NCT07128082), a fully remote, placebo-controlled phase 2 trial funded by the Schmidt Initiative for Long COVID, which enrolled 1,058 people in 73 days. Tirzepatide is titrated from 2.5 mg to 15 mg weekly, the primary outcome is fatigue (Fatigue Severity Scale) at 12 months, and results remain blinded. Preclinical studies show GLP-1 signaling can dampen microglial (brain immune cell) inflammation, but its relevance to Long COVID or POTS is unproven. These drugs are not recommended in severe gastroparesis, and their gastrointestinal effects and weight loss may be poorly tolerated by people who are already underweight.