Liraglutide associated with delayed gastric emptying, study finds

Liraglutide may affect weight loss through delayed gastric emptying of solids, according to a recent study.

Researchers performed a randomized, double-blind, placebo-controlled pilot trial at the Mayo Clinic in Rochester, Minn., to compare the effects of liraglutide and placebo on gastric motor function, satiation, satiety, and weight in obese patients over a 16-week period.

Patients 18 to 65 years of age with a body mass index (BMI) of at least 30 kg/m² were randomly assigned to receive subcutaneous liraglutide (3.0 mg) or placebo, with weekly dose escalation of 0.6 mg per day for five weeks, at which point the dose was maintained for the remainder of the study. All patients also received standardized nutritional and behavioral counseling.

The primary study outcome, change in gastric emptying of solids (defined as the time taken for half of a radiolabeled meal to empty from the stomach), was measured at five and 16 weeks in all patients who received at least one dose of the study drug. Missing data were imputed. Secondary outcomes included weight loss at week five and at week 16, satiation, satiety, and fasting and postprandial gastric volumes at 16 weeks. The study results were published online Sept. 25 by Lancet Gastroenterology & Hepatology.

From Dec. 18, 2015, to Sept. 1, 2016, 40 patients were enrolled in the study, with 19 assigned to the liraglutide group and 21 assigned to the placebo group. Median age was 37 years in the placebo group and 42 years in the liraglutide group; median BMI at baseline was 34.6 kg/m² and 37.2 kg/m², respectively. Gastric emptying of solids at five weeks was delayed in the liraglutide group compared with the placebo group (median time, 70 minutes vs. 4 minutes; P<0.0001). A similar finding was also seen at 16 weeks (median time, 30.5 minutes vs. −1 minutes; P=0.025). Participants in the liraglutide group also lost significantly more weight than those in the placebo group (median, 3.7 kg vs. 0.6 kg at five weeks [P<0.0001] and 5.3 kg vs. 2.5 kg at 16 weeks [P=0.0009]) and had lower satiation at 16 weeks, as measured by maximum tolerated volume (P=0.054). The groups did not differ significantly in volume to fullness, satiety, or fasting and postprandial gastric volumes at week 16. In a post hoc analysis, delayed gastric emptying appeared to be associated with weight loss. The most common adverse event in the liraglutide group was nausea (12 of 19 patients vs. 4 of 21 patients in the placebo group).

The authors noted that they could not prove a causal relationship between delayed gastric emptying of solids and weight loss with liraglutide and said that additional studies would be needed to determine the duration of this observed effect. However, they concluded that 12 weeks of daily liraglutide therapy plus brief counseling was associated with significant weight loss, significantly delayed gastric emptying of solids, and higher satiation versus placebo and that their results indicate a potential mechanism by which liraglutide affects weight loss.

“One intriguing implication of this study is that measurement of gastric emptying (eg, at 5 weeks of treatment) may be a biomarker of responsiveness to this class of drug,” the authors wrote. “This may help to select individuals for prolonged treatment with this relatively expensive drug or for cessation of treatment in those in whom there is no significant effect on this biomarker.”

An accompanying comment noted that the study raises several important questions that need answers, such as whether the delayed gastric emptying seen with liraglutide could be related to an autoimmune response and whether repeated treatment might be more cost-effective than continuous therapy. In the meantime, the comment author wrote, the study offers two important lessons: “First, obesity is not ‘all in the head’; the periphery (ie, the stomach) plays a pivotal part in its determinism. Second, there are effective medical alternatives to surgery we can offer to our patients with obesity.”