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

NCT07747805 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: IRB 25-1092Mandel MAG0024
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

COPD; Sarcopenia; Obesity & Overweight

Keywords

COPD; sarcopenia; obesity

Outcome Measures

Primary Outcomes (1)

• Change in FEV1

  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.

  12 months

Secondary Outcomes (6)

• Change in Hand Grip Strength

  6 months and 12 months

• Change in Six-Minute Walk Distance (6MWD)

  6 months and 12 months

• Change in Five Sit-to-Stand Performance

  6 months and 12 months

• Change in Lean Muscle Mass

  12 months

• Change in Serum Leptin Concentration

  6 months and 12 months

Study Arms (2)

COPD control

NO INTERVENTION

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.

COPD tirzepatide treatment

ACTIVE COMPARATOR

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.

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

Tirzepatide is a once-weekly subcutaneous dual GIP/GLP-1 receptor agonist administered for 52 weeks using standard dose escalation as tolerated in addition to standard clinical care.

COPD tirzepatide treatment

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 40-80 years
• Diagnosis of chronic obstructive pulmonary disease (COPD) with post-bronchodilator FEV₁/FVC \< 0.70
• GOLD stage 1-3 COPD (FEV₁ \>30% predicted)
• Former smoker with a smoking history of at least 10 pack-years
• Body mass index (BMI) ≥27 kg/m² with at least one weight-related comorbidity (e.g., prediabetes, hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease) or BMI 30-40 kg/m²
• Able and willing to provide written informed consent
• Able to comply with study procedures and follow-up visits

You may not qualify if:

• Type 2 diabetes mellitus (HbA1c \> 6.5%)
• Pregnancy or breastfeeding
• Coagulopathy, defined as INR \> 1.4 or platelet count \<80,000/μL
• Active malignancy, including lung cancer
• Use of medications known to significantly alter muscle protein metabolism within 6 weeks of enrollment (e.g., oral corticosteroids, tamoxifen, high-dose estrogen, testosterone)
• Personal or family history of medullary thyroid carcinoma
• Multiple endocrine neoplasia syndrome type 2 (MEN2)
• Known hypersensitivity or contraindication to tirzepatide or its components
• History of pancreatitis
• Severe gastrointestinal disease that, in the opinion of the investigator, would increase risk from study participation
• Significant diabetic retinopathy
• Clinically significant renal impairment
• Clinically significant gallbladder disease
• Current treatment with a DPP-4 inhibitor
• COPD exacerbation within 60 days prior to enrollment

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Related Publications (2)

• Hong Y, Lee JH, Jeong KW, Choi CS, Jun HS. Amelioration of muscle wasting by glucagon-like peptide-1 receptor agonist in muscle atrophy. J Cachexia Sarcopenia Muscle. 2019 Aug;10(4):903-918. doi: 10.1002/jcsm.12434. Epub 2019 Apr 24.

  PMID: 31020810 BACKGROUND

• Foer D, Strasser ZH, Cui J, Cahill KN, Boyce JA, Murphy SN, Karlson EW. Association of GLP-1 Receptor Agonists with Chronic Obstructive Pulmonary Disease Exacerbations among Patients with Type 2 Diabetes. Am J Respir Crit Care Med. 2023 Nov 15;208(10):1088-1100. doi: 10.1164/rccm.202303-0491OC.

  PMID: 37647574 BACKGROUND

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Obesity; Overweight; Sarcopenia

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Amy Attaway, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Amy Attaway, MD

CONTACT

216-445-2807; attawaa@ccf.org

Lian Yang

CONTACT

216-445-5441; YANGL2@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff

Study Record Dates

• First Submitted: July 31, 2026
• First Posted: August 5, 2026
• Study Start (Estimated): August 28, 2026
• Primary Completion (Estimated): August 15, 2028
• Study Completion (Estimated): August 15, 2029
• Last Updated: August 5, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)