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

• Published in: Diabetes, obesity & metabolism Vol. 20; no. 11; pp. 2557 - 2564
• Main Authors: Nexøe‐Larsen, Christina C., Sørensen, Pernille H., Hausner, Helene, Agersnap, Mikkel, Baekdal, Mille, Brønden, Andreas, Gustafsson, Lea N., Sonne, David P., Vedtofte, Louise, Vilsbøll, Tina, Knop, Filip K.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.11.2018; Wiley Subscription Services, Inc
• Subjects: Adolescent; Adult; Antidiabetics; antiobesity drug; Body mass index; Body weight; clinical trial; Constipation; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Double-Blind Method; Evidence-based medicine; Female; Gallbladder; Gallbladder Emptying - drug effects; Gastrointestinal diseases; GLP‐1; GLP‐1 analogue; Humans; liraglutide; Liraglutide - pharmacology; Liraglutide - therapeutic use; Male; Middle Aged; Nausea; Obesity; Obesity - complications; Obesity - metabolism; Obesity - physiopathology; obesity therapy; Original; Overweight; Overweight - complications; Overweight - metabolism; Overweight - physiopathology; Physical activity; Placebos; Postprandial Period - drug effects; Young Adult; clinical trial; liraglutide; antiobesity drug; GLP-1; obesity therapy; GLP-1 analogue
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.13420

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.