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

Status

Not yet recruiting

Phase

Phase 2

Enrollment

30 participants (estimated)

Sponsor

The Cleveland Clinic · Other

Design

Randomized · Open label (no masking)

Countries

1 country

United States

Start

28 Aug 2026 (estimated)

Primary completion

15 Aug 2028 (estimated)

Completion

15 Aug 2029 (estimated)

First posted

5 Aug 2026

Last update posted

5 Aug 2026

Conditions

COPD · Obesity & Overweight · Sarcopenia

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 therapy on skeletal muscle mitochondrial function and fatty acid oxidation using muscle biopsies obtained at baseline and 12 months, combined with high-resolution respirometry, transcriptomics, metabolomics, and proteomics. Third, we will assess changes in clinical outcomes including lung function, body composition, muscle strength, and physical performance. Participants will undergo comprehensive phenotyping that includes spirometry, respiratory muscle strength testing, six-minute walk testing, handgrip strength, sit-to-stand testing, body composition assessment, diaphragm ultrasound, and non-contrast CT imaging of the lungs and thighs. Blood samples will be collected for biomarker, proteomic, metabolomic, genomic, and immunologic analyses. Vastus lateralis muscle biopsies will be performed at baseline and study completion to evaluate mitochondrial bioenergetics and molecular pathways associated with muscle remodeling. Eligible participants will be adults aged 40-80 years with COPD, a smoking history of at least 10 pack-years, and overweight or obesity. Individuals with diabetes, active malignancy, recent COPD exacerbations, contraindications to tirzepatide, or conditions that could interfere with study participation will be excluded. This pilot study is designed to generate critical mechanistic and clinical data regarding the role of GLP-1 receptor agonists in COPD. Findings will help define the relationships among obesity, adipokine signaling, systemic inflammation, skeletal muscle dysfunction, and lung disease progression, while providing preliminary efficacy estimates to support the design of a future multicenter randomized clinical trial evaluating GLP-1 therapy as a novel treatment strategy for COPD.

• No intervention

  COPD control

  Participants with COPD and overweight or obesity who will not receive tirzepatide and will continue standard clinical care. Participants will complete the same research assessments as the intervention group, including blood collection, pulmonary function testing, physical performance testing, body composition assessments, imaging, and skeletal muscle biopsies, allowing comparison of clinical and biological changes over 12 months.

• Active comparator

  COPD tirzepatide treatment

  Participants with COPD and overweight or obesity will receive once-weekly subcutaneous tirzepatide for 52 weeks in addition to standard clinical care. Participants will undergo longitudinal assessments of lung function, skeletal muscle health, body composition, physical performance, and inflammatory biomarkers to evaluate the effects of tirzepatide on pulmonary and systemic manifestations of COPD.

1. Change in FEV1

   Time frame · 12 months

   Registry description

   Change in post-bronchodilator forced expiratory volume in one second (FEV₁) measured by standardized spirometry. FEV₁ will be compared between participants receiving tirzepatide and control participants.