Evaluating the Effects of GLP-1 Receptor Agonists on Long-COVID Outcomes: A Comparative Analysis Using TriNetX

Background and/or Objectives: Long-COVID is a persistent, multisystem condition with limited treatment options. This study explores the potential benefits of GLP-1 receptor agonists (GLP-1RAs) on mortality, cardiovascular events, and chronic symptoms in Long-COVID patients.

Design: Propensity score matched retrospective cohort analysis.

Setting : Using de-identified electronic health record data accessed via TriNetX, we compared outcomes in patients with Long-COVID following with confirmed SARS-CoV-2 and prescribed a GLP-1RA to patients with the same Long-COVID control who were not prescribed GLP-1RAs. This is exempt from IRB review as determined by the University of Texas Medical Branch.

Participants : Two cohorts (n = 8,602 each) within a 5-year period were defined: Cohort 1 contained patients with Long-COVID (ICD-10: U09.9) following a positive SARS-CoV-2 test who were prescribed one of six most commonly prescribed GLP-1RAs, and Cohort 2 contained the Long-COVID control who were not prescribed any GLP-1RAs.

Interventions: N/A

Main Outcome Measures: We investigated the effects of GLP-1RAs on the incidences of mortality, cardiovascular events (myocardial infarction (MI), atrial fibrillation, and deep vein thrombosis/pulmonary embolism (DVT/PE)), chronic conditions (chronic fatigue syndrome (CFS) and fibromyalgia), and metabolic conditions (diabetes and hyperlipidemia) in Long-COVID patients.

Results: GLP-1RA users had a lower mortality rate of 2.0% versus 5.9% in controls (HR: 0.328; p< 0.001). Cardiovascular events were also reduced including MI (3.6% versus 4.5%), DVT/PE (5.5% vs. 6.8%), and atrial fibrillation (9.5% vs. 12.7%). CFS risk decreased to 2.7% versus 4.3%. Fibromyalgia (8.0% versus 7.1%), diabetes (52.5% versus 38.9%) and hyperlipidemia (43.0% versus 37.4%) were more prevalent in the GLP-1RA group.

Conclusions: This study suggests GLP-1RAs are associated with lower mortality and cardiovascular risks in Long-COVID patients. There is potential benefit for CFS though a slight increase in fibromyalgia warrants further investigation. We suggest randomized controlled trials to assess the role of GLP-1 RAs in Long-COVID therapeutics.