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

Diabetes Obes Metab. 2018 Nov;20(11):2557-2564. doi: 10.1111/dom.13420. Epub 2018 Jul 10.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Double-Blind Method
  • Female
  • Gallbladder Emptying / drug effects*
  • Humans
  • Liraglutide / pharmacology*
  • Liraglutide / therapeutic use
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / metabolism
  • Obesity / physiopathology*
  • Overweight / complications
  • Overweight / metabolism
  • Overweight / physiopathology*
  • Placebos
  • Postprandial Period / drug effects
  • Young Adult

Substances

  • Placebos
  • Liraglutide