Effects of Glucagon-like peptide-1 receptor agonist treatment on pulmonary function and quality of life in obese patients with chronic obstructive pulmonary disease

Ayse Dudu Altintas Dogan

Research output: ThesisPh.D. thesis

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Abstract

Obesity and chronic obstructive pulmonary disease (COPD) are bothconditions with increased inflammatory activity and both conditions showsincreasing prevalence worldwide. Glucagon-like peptide 1 (GLP-1) is a gutincretin hormone participating in glucose homeostasis. GLP-1 receptoragonists (GLP-1 RA) are indicated for the treatment of T2D and weight losstreatment. Recent studies have shown that GLP-1 receptors are present invarious tissues of the body. GLP-1 RA thus have the potential to counteract the effect of inflammation. This is supported by studies in animal, human,and laboratory settings.

We conducted a randomized clinical trial including 40 persons with obesity and COPD over a study period of 44 weeks. We evaluated the effect of treatment with liraglutide on weight, lung function, inflammation, obstructive sleep apnea and health related quality of life (HRQoL).

First, we investigated the effect of treatment with liraglutide on various pulmonary outcomes derived from spirometry, body plethysmography, COPD assessment test and 6 minutes walking distance. We found, that treatment with liraglutide improved FVC, DLCO and CAT-score, but did not reveal significant changes on FEV1, FEV1/FVC and 6 minutes walking distance.

Secondly, we investigated the effect of treatment with liraglutide on pulmonary inflammation by quantifying inflammation with FDG-PET/CT and measuring systemic inflammation markers. FDG-PET/CT is increasingly used to diagnose various infectious and inflammatory diseases by assessing metabolic activity.

We hypothesized, that treatment with liraglutide would decrease pulmonary inflammation assessed with FDG-PET/CT and reduce systemic inflammation by decreasing circulating systemic inflammatory markers. We used SUV, SUL and TLG as surrogate measures for pulmonary inflammation before and after treatment. There were no significant changes in SUV, SUL or TLG after treatment with liragutide. Unlike other studies, we found that FDG-PET/CT is not useful for quantifying inflammation in this population. We measured inflammation markers regularly throughout the study. CRP and MCP-1 were in normal range and IL-6 was only slightly elevated before, under and after treatment with liraglutide. We did not find any significant changes in inflammation markers after treatment with liraglutide.

Thirdly, we investigated the effect of treatment with liraglutide on
obstructive sleep apnea (OSA) and HRQoL. We found a high prevalence of OSA in our population. Stratifying them in subgroups depending on the severity and treatment of OSA, we found that treatment with liraglutide improved apnea hypopnea index in people with mild OSA and reduced oxygen desaturation index in people with moderate to severe OSA. Using SF-36v2, we investigated the effect of treatment on HRQoL. We did not find significant changes in the main summary measures, but we found a significant improvement in two of the eight health domains including general health and role physical.

Original languageEnglish
Awarding Institution
  • University of Southern Denmark
Supervisors/Advisors
  • Juhl, Claus Bogh, Principal supervisor
  • Hilberg, Ole, Co-supervisor
  • Hess, Søren, Co-supervisor
Date of defence20. Jan 2023
Publisher
DOIs
Publication statusPublished - 15. Dec 2022

Note re. dissertation

Print copy of the full thesis is restricted to reference use in the Library

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