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

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.

Teduglutide improves liver chemistries in short bowel syndrome–associated intestinal failure: Post hoc analysis

“…Importantly, the related glucagon-like peptide-1 receptor agonists have recently been utilized for the treatment of nonalcoholic steatohepatitis, 22 although these therapies likely act via divergent pathways. 23 The main study strength is the analysis of detailed clinical trial data from a heterogeneous population. The main study limitation was a small sample size, which precludes subgroup analyses.…”

“…Improvements in liver chemistries were independent of reductions in PN/IV or changes in BMI. Importantly, the related glucagon‐like peptide‐1 receptor agonists have recently been utilized for the treatment of nonalcoholic steatohepatitis, 22 although these therapies likely act via divergent pathways 23 …”

Weight reduction and the risk of gallbladder and biliary disease: A systematic review and meta‐analysis of randomized clinical trials

“…Experimental studies demonstrated that the postprandial FGF19 and GLP-2 concentrations were decreased and postprandial cholecystokinin was increased with GLP-1 analog use, which may result in delayed postprandial gallbladder refilling. 18 Cholangiocytes are susceptible to GLP-1 and respond with increased proliferation and functional activity, which may increase the risk of duct obstruction. 19,20 These findings all provided strong evidence for the association between GLP-1 RA treatment and gallbladder and biliary disease adverse effect.…”

“…In addition to the weight loss effect of GLP‐1 analogs, independent mechanisms with the use of GLP‐1 analogs may also contribute to the increased risk of gallbladder and biliary disease. Experimental studies demonstrated that the postprandial FGF19 and GLP‐2 concentrations were decreased and postprandial cholecystokinin was increased with GLP‐1 analog use, which may result in delayed postprandial gallbladder refilling 18 . Cholangiocytes are susceptible to GLP‐1 and respond with increased proliferation and functional activity, which may increase the risk of duct obstruction 19,20 .…”

How traditional Chinese medicine can prevent recurrence of common bile duct stones after endoscopic retrograde cholangiopancreatography?

“…The body regulates the biliary system through humoral hormones and other cytokines, including cholecystokinin (CCK), which stimulates gallbladder contraction and bile secretion, as well as GLP-2 and FGF19, which promote gallbladder relaxation ( Choi et al, 2006 ; Yusta et al, 2017 ; Metry et al, 2023 ). The secretion of these hormones and signaling molecules is closely linked to bile acids in the gut ( Hansen et al, 2020 ; Miedzybrodzka et al, 2021 ; Nerild et al, 2023 ). The diastole of the gallbladder ensures the normal excretion of bile salts, cholesterol and phospholipids from the liver cells in order to reduce the amount of cholesterol in the serum and tissues of the body; while the regular contraction of the gallbladder ensures the power of the bile flow in the biliary system and reduces the time of bile retention, thus decreasing the probability of gallstones occurrence.…”