Short summary

Obesity and COPD are both common conditions. The GLP-1 receptor agonist Liraglutide is widely used for diabetes type 2 and for weight loss. Recently studies shows anti-inflammatory effects of Liraglutide. COPD is characterized by pulmonary inflammation and anti-inflammatory treatment is thus a cornerstone in the treatment of COPD. Targeting both obesity and inflammation, Liraglutide 3 mg daily constitute a new option for the treatment of obese COPD patients.

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Rationale

Chronic obstructive pulmonary disease (COPD) and obesity are both very common conditions. Thus, in 2008 approximately 35% of all adults were overweight (BMI>25 kg/m2), and 12 % were obese (BMI>30 kg/m2). Further, according to the latest WHO estimates from 2004, 64 million people have COPD and 3 million died from COPD which is accordingly projected to be the third leading cause of death worldwide in 2030. Estimates of obesity in COPD range from 18% to as much as 54%. While low body weight and weight loss are poor prognostic factors in COPD, possibly due to the association with disease progression, obesity in COPD is associated with greater restriction of daily activities, increased risk of comorbidities, hospitalization, and reduced quality of life. The most effective treatment for obesity is bariatric surgery. Surgically induced weight loss has been shown in many studies to improve respiratory symptoms in obese patients with COPD. Severe COPD, however, constitutes a contraindication for bariatric surgery. Other means of weight loss are often insufficient to provide a significant and lasting effect, although a recent study provides evidence that even a modest BMI reduction of 2.4 kg/m2 resulted in significant improvement in measures of pulmonary function and quality of life. The GLP-1 receptor agonist Liraglutide is widely used for the treatment of type 2 diabetes. In a dosage of 3 mg Liraglutide is additionally approved for weight loss therapy in severely obese patients irrespective of the presence of type 2 diabetes. Liraglutide 3 mg resulted in a 5.6 kg weight loss in excess to placebo in people with obesity, and 63% of people in the Liraglutide group lost more than 5% of their total body weight. Also, the fact that people with obstructive sleep apnea improves their Apnea-Hypopnea-Index significantly after 32 weeks of Liraglutide treatment compared to placebo, indicates that the effects of Liraglutide induced weight loss reach beyond the weight loss per se and the metabolic effects as seen in T2D.

COPD severity and progression are influenced by a long list of both pro-inflammatory and anti-inflammatory cytokines. Anti-inflammatory treatment is therefore a cornerstone both in disease control and treatment of acute exacerbation of COPD. Anti-inflammatory treatment is usually based on the use of corticosteroids for either oral or inhalation therapy. Although effective, this treatment is associated with adverse events ranging from oral candidiasis to osteoporosis and secondary adrenal failure after long term systemic therapy. Recently, Liraglutide has attracted interest due to its anti-inflammatory effects (cell culture studies, mice studies). Altogether, since weight loss and modulation of the inflammatory response to obesity both have positive impact on pulmonary symptoms and quality of life in obese patients with COPD, Liraglutide 3mg may constitute an intriguing new option for the treatment of obese COPD patients. 

COPD is a common disease characterized by pulmonary inflammation, reduced pulmonary capacity, reduced physical activity and quality of life. Obesity is likewise a common disease characterized by inflammation, reduced physical activity and quality of life. Targeting both obesity and inflammation may turn out beneficial for patients with COPD and obesity, and this study explore the possibility to reverse a vicious cycle of COPD, lack of physical activity and obesity. The primary objective of the study is to evaluate the effect of Liraglutide 3mg in patients with COPD on patient reported outcomes as measured by the Transition Dyspnea Index. We hypothesize that Liraglutide 3mg exerts beneficial effects on measures of pulmonary function and quality of life in overweight patients with COPD by reducing body weight and reducing inflammatory activity.

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Description of the cohort

• Adults 30-75 years old. 
• COPD defined by FEV1/FVC < 70 % after max. bronchodilatation
• BMI > 27 
• Women of childbearing potential must use safe anticontraceptiva

Data and biological material

• Physical examination: EKG, blood pressure, weight, height, waist, hip
• Blood samples with inflammation markers
• Spirometry + CO diffusion
• Sleep apnea
• 6 minutes walking test
• FDG-PET-CT 
• Questionnaires
• Concomitant medication

Collaborating researchers and departments

Department of Medicine, Section of Endocrinology, Hospital of South West Jutland

• Consultant Claus Bogh Juhl

Department of Medicine, Section of Pulmonary Diseases, Lillebaelt Hospital

• Professor Ole Hilberg

Department of Medicine, Section of Pulmonary Diseases, Hospital of South West Jutland

• Senior Consultant Torben Tranborg Jensen

Department of Public Health, Unit for Thrombosis Research, OUH, Department of Clinical Biochemistry, Hospital of South West Jutland

• Else Marie Bladbjerg

Department of Radiology and Nuclear Medicine, Hospital of South West Jutland

• Associate Professor Søren Hess

Department of Medicine, Section of Endocrinology, Hospital of South West Jutland

• Associate Professor Jeppe Gram