Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility |
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| Authors: | Henriette H. Nerild MD Andreas Brønden MD Ida M. Gether MD Pernille H. Hellmann MD Mille Baekdal MD Matthew P. Gillum PhD Jens S. Svenningsen Bolette Hartmann PhD Naveen Rathor MD Hanna Angelene Kudiyanur Muniraju MSc Jens F. Rehfeld MD Jens J. Holst MD Tina Vilsbøll MD David P. Sonne MD Filip K. Knop MD |
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| Affiliation: | 1. Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark;2. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;3. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark;4. Novo Nordisk, Copenhagen, Denmark;5. Novo Nordisk Global Business Services, Bangalore, India;6. Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;7. Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark |
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| Abstract: | Aim Liraglutide treatment is associated with gallbladder-related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 2 (GLP-2), are known to regulate gallbladder motility and may be implicated in gallbladder-related disorders associated with liraglutide treatment. Materials and Methods In a double-blind, 12-week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4 kg/m2 (mean ± standard deviation)] with obesity were randomized 1:1 to once-daily subcutaneous liraglutide (escalated from 0.6 mg to 3.0 mg once-daily) or placebo. During liquid meal tests performed at baseline, after the first dose and following 12 weeks of treatment, we evaluated postprandial gallbladder dynamics and plasma responses of CCK, FGF19 and GLP-2. Results Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)0-240 min 24.8 vs. 48.0 min × ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC0-240 min 33.7 vs. 48.5 ng/ml × min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP-2 responses (AUC0-240 min 3650 vs. 4894 min × pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC0-240 min 3760 vs. 4882 min × pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC0-240 min 762 vs. 670 min × pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC0-240 min 873 vs. 628 min × pmol/L; TR 1.39 (1.12; 1.73)]. Conclusion Compared with placebo, treatment with liraglutide decreased postprandial FGF19 and GLP-2 concentrations and increased postprandial CCK concentrations, which may explain the delayed postprandial gallbladder refilling observed in individuals with obesity treated with liraglutide. |
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| Keywords: | clinical trial GLP1 GLP-1 analogue incretin physiology incretin therapy liraglutide |
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