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

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/m(2) 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 (GBEF(max)), 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/m(2), 50% women). Mean 12-week GBEF(max) (treatment difference -3.7%, 95% confidence interval [CI] -13.1, 5.7) and area under the GBEF curve in the first 60 minutes (-390% x min, 95% CI -919, 140) did not differ for liraglutide 3.0 mg (n = 23) vs placebo (n = 24). The median (range) time to GBEF(max) 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 GBEF(max) but appeared to prolong the time to GBEF(max).