Effects of liraglutide on gallbladder emptying: A randomized, placebo-controlled trial in adults with overweight or obesity

Abstract

Aims: Treatment with liraglutide 3.0 mg has been associated with gallbladder-related adverse events. To conduct a single-centre, double-blind, 12-week trial comparing the effect of 0.6 mg liraglutide and steady-state liraglutide 3.0 mg with placebo on gallbladder emptying in adults with body mass index (BMI) ≥27 kg/m2 and without diabetes.

Methods: Participants were randomized 1:1 to once-daily subcutaneous liraglutide (n = 26) or placebo (n = 26), starting at 0.6 mg with 0.6-mg weekly increments to 3.0 mg, with nutritional and physical activity counselling. A 600-kcal (23.7 g fat) liquid meal test was performed at baseline, after the first dose and after 12 weeks. The primary endpoint was the 12-week maximum postprandial gallbladder ejection fraction (GBEFmax ), measured over 240 minutes after starting the meal.

Results: Baseline characteristics were similar between groups (mean ± SD overall age 47.6 ± 10.0 years, BMI 32.6 ±3.4 kg/m2 , 50% women). Mean 12-week GBEFmax (treatment difference -3.7%, 95% confidence interval [CI] -13.1, 5.7) and area under the GBEF curve in the first 60 minutes (-390% × min, 95% CI -919, 140) did not differ for liraglutide 3.0 mg (n = 23) vs placebo (n = 24). The median (range) time to GBEFmax was 151 (11-240) minutes with liraglutide 3.0 mg and 77 (22-212) minutes with placebo. Similar findings were noted after the first 0.6-mg liraglutide dose. Gastrointestinal disorders, notably nausea and constipation, were the most frequently reported adverse events.

Conclusions: Treatment with liraglutide did not affect the GBEFmax but appeared to prolong the time to GBEFmax .

Keywords: GLP-1; GLP-1 analogue; antiobesity drug; clinical trial; liraglutide; obesity therapy.

Conflict of interest statement

H.H., M.A. and L.N.G. are employed by Novo Nordisk and H.H. and L.N.G. hold stock in the company. C.C.N., P.H.S., M.B., A.B., D.P.S., L.V. and T.V. have no conflicts of interest to disclose. Within the past 36 months, F.K.K. has served on scientific advisory panels and/or speaker's bureaus for, served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck Sharp & Dohme, Norgine, Novo Nordisk, Sanofi and Zealand Pharma.

© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1

Trial design. Daily dosing started at 0.6 mg of treatment followed by dose escalation of 0.6 mg weekly increments to 3.0 mg. The meal tests took place at baseline and on days 2 and 85. Screening took place 2 to 28 days before the first meal test

Figure 2

A, Gallbladder volume and B, ejection fraction profiles. Data are observed means, and error bars represent the standard error of the mean. The gallbladder ejection fraction (GBEF) values were, for each timepoint, calculated from the gallbladder volume (as change from the fasting gallbladder volume) as: GBEF(t) = 100% × (volfasting − vol(t))/volfasting, where t = time and vol = volume