GLP-1 Agonists for Lung Function Improvement and Muscle Restoration in COPD

Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation, obesity-related metabolic dysfunction, skeletal muscle impairment, and progressive decline in lung function. While obesity has historically been viewed as protective in COPD, emerging evidence suggests that excess adiposity and adipokine dysregulation, particularly elevated leptin levels, contribute to chronic inflammation, impaired muscle function, and worse clinical outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated anti-inflammatory, metabolic, and potential muscle-preserving effects beyond weight loss, making them promising therapeutic candidates for COPD. The GLIMR COPD study is a prospective, randomized, controlled pilot trial designed to evaluate the effects of tirzepatide on lung function, skeletal muscle health, inflammation, and body composition in overweight and obese adults with COPD. Thirty participants will be enrolled at the Cleveland Clinic COPD Center, including 20 participants receiving tirzepatide and 10 age- and sex-matched control participants. Study participants will be followed for 12 months with assessments performed at screening, baseline, 6 months, and 12 months. Tirzepatide-treated participants will undergo standard dose escalation to a maintenance dose of 2.4 mg weekly. The primary objective is to determine the effect of GLP-1 receptor agonist therapy on skeletal muscle function and physiology over 12 months. Secondary objectives include evaluating changes in body composition, systemic inflammation, adipokine signaling, immune function, pulmonary physiology, physical performance, and treatment tolerability. The study is built around three mechanistic aims. First, we will characterize the effects of GLP-1 therapy on systemic inflammation and immune dysregulation using longitudinal blood-based proteomic analyses and adipokine measurements, including leptin and adiponectin. Second, we will investigate the impact of GLP-1 th