4.7 Article

Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility

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DIABETES OBESITY & METABOLISM
卷 25, 期 6, 页码 1632-1637

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WILEY
DOI: 10.1111/dom.15017

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clinical trial; GLP1; GLP-1 analogue; incretin physiology; incretin therapy; liraglutide

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In this study, it was found that Liraglutide treatment is associated with gallbladder-related disorders and can delay postprandial gallbladder refilling. The gut hormones CCK, FGF19, and GLP-2, which regulate gallbladder motility, may be implicated in these disorders.
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/m(2) (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 x ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC(0-240 min) 33.7 vs. 48.5 ng/ml x min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP-2 responses (AUC(0-240 min) 3650 vs. 4894 min x pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC(0-240 min) 3760 vs. 4882 min x pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC(0-240 min) 762 vs. 670 min x pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC(0-240 min) 873 vs. 628 min x 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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