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      International Journal of COPD (submit here)

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      Respiratory Effects of Treatment with a Glucagon-Like Peptide-1 Receptor Agonist in Patients Suffering from Obesity and Chronic Obstructive Pulmonary Disease

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          Abstract

          Purpose

          Chronic obstructive pulmonary disease (COPD) affects millions of people worldwide. Obesity is commonly seen concomitantly with COPD. People with COPD have reduced quality of life, reduced physical activity, chronic respiratory symptoms, and may suffer from frequent clinical exacerbations. Liraglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) approved for weight loss and treatment of type-2 diabetes mellitus. In addition, liraglutide exerts anti-inflammatory actions by reducing IL-6 and MCP-1 levels. We investigated the effect of liraglutide on pulmonary function in people suffering from obesity and COPD.

          Patients and Methods

          In this controlled, double-blind trial, 40 people with obesity and COPD from two outpatient clinics were allocated randomly to receive liraglutide (3.0 mg, s.c.) or placebo (s.c.) for 40 weeks. At baseline and after 4, 20, 40, and 44 weeks, participants underwent pulmonary-function tests, 6-min walking test, and replied to a questionnaire regarding the clinical impact of COPD (COPD assessment test (CAT)-score).

          Results

          Compared with placebo, liraglutide use resulted in significant weight loss, increased forced vital capacity (FVC) and carbon monoxide diffusion capacity, and improved CAT-score. We found no significant changes in forced expiratory volume in one second (FEV 1), FEV 1/FVC, or 6-min walking distance.

          Conclusion

          In patients suffering from obesity and COPD, 40 weeks of treatment with liraglutide improved some measures of pulmonary function. Our study suggests that liraglutide at 3.0 mg may be appropriate treatment in patients with obesity and COPD.

          Most cited references28

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          A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management.

          Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagon-like peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously.
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            The physiology of glucagon-like peptide 1.

            Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before the hormone has left the gut, raising the possibility that the actions of GLP-1 are transmitted via sensory neurons in the intestine and the liver expressing the GLP-1 receptor. Because of this, it is important to distinguish between measurements of the intact hormone (responsible for endocrine actions) or the sum of the intact hormone and its metabolites, reflecting the total L-cell secretion and therefore also the possible neural actions. The main actions of GLP-1 are to stimulate insulin secretion (i.e., to act as an incretin hormone) and to inhibit glucagon secretion, thereby contributing to limit postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the "ileal brake" mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists are currently being evaluated for the therapy of type 2 diabetes. Decreased secretion of GLP-1 may contribute to the development of obesity, and exaggerated secretion may be responsible for postprandial reactive hypoglycemia.
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              Incretin hormones: Their role in health and disease.

              Incretin hormones are gut peptides that are secreted after nutrient intake and stimulate insulin secretion together with hyperglycaemia. GIP (glucose-dependent insulinotropic polypeptide) und GLP-1 (glucagon-like peptide-1) are the known incretin hormones from the upper (GIP, K cells) and lower (GLP-1, L cells) gut. Together, they are responsible for the incretin effect: a two- to three-fold higher insulin secretory response to oral as compared to intravenous glucose administration. In subjects with type 2 diabetes, this incretin effect is diminished or no longer present. This is the consequence of a substantially reduced effectiveness of GIP on the diabetic endocrine pancreas, and of the negligible physiological role of GLP-1 in mediating the incretin effect even in healthy subjects. However, the insulinotropic and glucagonostatic effects of GLP-1 are preserved in subjects with type 2 diabetes to the degree that pharmacological stimulation of GLP-1 receptors significantly reduces plasma glucose and improves glycaemic control. Thus, it has become a parent compound of incretin-based glucose-lowering medications (GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4 or DPP-4). GLP-1, in addition, has multiple effects on various organ systems. Most relevant are a reduction in appetite and food intake, leading to weight loss in the long term. Since GLP-1 secretion from the gut seems to be impaired in obese subjects, this may even indicate a role in the pathophysiology of obesity. Along these lines, an increased secretion of GLP-1 induced by delivering nutrients to lower parts of the small intestines (rich in L cells) may be one factor (among others like peptide YY) explaining weight loss and improvements in glycaemic control after bariatric surgery (e.g., Roux-en-Y gastric bypass). GIP and GLP-1, originally characterized as incretin hormones, have additional effects in adipose cells, bone, and the cardiovascular system. Especially, the latter have received attention based on recent findings that GLP-1 receptor agonists such as liraglutide reduce cardiovascular events and prolong life in high-risk patients with type 2 diabetes. Thus, incretin hormones have an important role physiologically, namely they are involved in the pathophysiology of obesity and type 2 diabetes, and they have therapeutic potential that can be traced to well-characterized physiological effects.
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                Author and article information

                Journal
                Int J Chron Obstruct Pulmon Dis
                Int J Chron Obstruct Pulmon Dis
                copd
                International Journal of Chronic Obstructive Pulmonary Disease
                Dove
                1176-9106
                1178-2005
                22 February 2022
                2022
                : 17
                : 405-414
                Affiliations
                [1 ]Department of Medicine, Hospital South West Jutland, University Hospital of Southern Denmark , Esbjerg, Denmark
                [2 ]Department of Regional Health Research, Faculty of Health Sciences, University of Southern Denmark , Odense, Denmark
                [3 ]Department of Medicine, Lillebaelt Hospital, University Hospital of Southern Denmark , Vejle, Denmark
                [4 ]Department of Radiology and Nuclear Medicine, Hospital South West Jutland, University Hospital of Southern Denmark , Esbjerg, Denmark
                [5 ]Unit for Thrombosis Research, Department of Clinical Biochemistry, Hospital South West Jutland, University Hospital of Southern Denmark , Esbjerg, Denmark
                [6 ]Steno Diabetes Center , Odense, Denmark
                Author notes
                Correspondence: Ayse Dudu Altintas Dogan, Department of Medicine, Hospital South West Jutland, University Hospital of Southern Denmark , Finsensgade 35, Esbjerg, 6700, Denmark, Tel +45 22 71 50 90, Email ayse.dudu.altintas.dogans@rsyd.dk
                Author information
                http://orcid.org/0000-0001-6953-9969
                http://orcid.org/0000-0003-0912-2437
                Article
                350133
                10.2147/COPD.S350133
                8882670
                35237033
                431aea27-9f3e-4962-9bd3-7a08b02eac04
                © 2022 Altintas Dogan et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 27 November 2021
                : 03 February 2022
                Page count
                Figures: 1, Tables: 5, References: 29, Pages: 10
                Funding
                Funded by: Novo Nordisk, open-funder-registry 10.13039/501100004191;
                Study medication and running costs were provided by Novo Nordisk as a part of the Investigator Sponsored Studies Program. We also had financial support from Karola Jørgensens Forskningsfond, Research Council of Hospital South West Jutland, University Hospital of Southern Denmark, and Region of Southern Denmark.
                Categories
                Original Research

                Respiratory medicine
                glp-1 ra,copd,obesity,inflammation,spirometry
                Respiratory medicine
                glp-1 ra, copd, obesity, inflammation, spirometry

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