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

Abstract

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. In a double-blind, 12-week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4kg/m2 (mean ± standard deviation)] with obesity were randomized 1:1 to once-daily subcutaneous liraglutide (escalated from 0.6mg to 3.0mg 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. Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)0-240 min 24.8 vs. 48.0min× 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. 48.5ng/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)]. 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.