The study is a 44 weeks, prospective, randomized, placebo-controlled, double-blinded, parallel group two-center trial. Forty patients are recruited among the outpatients of the chronic obstructive pulmonary disease (COPD) clinic, Hospital of South West Jutland and Lillebælt Hospital according to the inclusion and exclusion criteria. The patients are randomized to receive liraglutide 3 mg per day (initial dose 0.6 mg, increasing by 0.6 mg weekly until 3 mg is reached) or placebo. At baseline, after four weeks (assessment of the acute effect of liraglutide), 20 weeks, and 40 weeks (assessment of the combined effect of liraglutide and weight loss) and at week 44 (assessment of the weight-loss after discontinuation of liraglutide) the patients are assessed by physical examination, carbon monoxide (CO) diffusion test, pulmonary function test, biomarkers of inflammation (CRP, interleucine-6 (IL-6), monocyte chemitactic protein-1 (MCP-1)), Fluorodeoxyglucose (FDG)/PET-CT scan of the lungs, 6-minute walking test, respiratory polygraphy and validated questionnaires including basic dyspnea index, transition dyspnea index, COPD Assessment Test (CAT)-score, short-form-36 (SF-36) and Epworth Sleepiness Score.

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. The hypothesis is 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.

Inclusion Criteria:

1. Informed consent obtained before any trial-related activities
2. COPD as defined by FEV1/FVC<70% after maximal broncho-dilatation and in accordance with the Gold guidelines 2017 (25)
3. Previous smoking of ≥ 20 pack-years
4. Overweight defined as BMI > 27 kg/m2
5. Age 30 - 75 years
6. Women of childbearing potential must use a safe anti-contraceptive method

Exclusion Criteria:

1. Chronic treatment with systemic steroids (inhalation steroids allowed)
2. Current smokers
3. Diabetes mellitus type 1 and type 2 as defined by current or previous treatment with antidiabetic medications of any kind or HbA1c ≥ 48mmol/mol
4. Severe hepatic disease (Alanine transferase > 3 x UNL)
5. Severe impaired renal function (eGFR < 30ml/min)
6. Congestive heart disease New York Heart Association (NYHA) class 3-4
7. History of acute or chronic pancreatitis
8. History of cholecystitis or cholecystolithiasis
9. Pregnant or breastfeeding women
10. Known bronchial asthma or interstitial lung disease
11. Family history of multiple endocrine neoplasia type 2 (MEN2) or medullary thyroid carcinoma
12. Large goiter or plasma-calcitonin > 50ng/ml