Liraglutide's weight-loss effects linked to delay in gastric emptying

Last Updated: 2017-10-04

By Anne Harding

NEW YORK (Reuters Health) - Liraglutide slows gastric emptying and lowers satiety threshold, a 16-week study in obese people shows.

Gastric emptying delay also was positively associated with weight loss, Dr. Michael Camilleri of Mayo Clinic in Rochester, Minnesota, and colleagues found. "We're finding that it actually has an effect on stomach emptying, and it also has an effect on how much people can eat before they feel full," Dr. Camilleri told Reuters Health in a telephone interview.

Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, which the U.S. Food and Drug Administration (FDA) approved at a 1.2-mg dose for treating type 2 diabetes (Victoza) in 2010 - and at a 3-mg dose for treating obesity (Saxenda) this past April.

Proposed mechanisms through which GLP-1 may contribute to weight loss include slowing gastric emptying, increasing satiety, boosting resting energy, and acting directly on appetite centers in the brain, Dr. Camilleri and his team note in their report.

To investigate the role of gastric emptying, the researchers randomly assigned 40 patients with a body-mass index of 30 or higher to receive liraglutide or placebo. At five weeks, liraglutide recipients had a 70-minute delay, on average, in gastric emptying (vs. 4 minutes for the placebo group), while at 16 weeks gastric emptying was delayed by 30.5 minutes (vs. a 1-minute increase with placebo).

The liraglutide patients lost a median 3.7 kilograms at five weeks and 5.3 kilograms at 16 weeks, versus 0.6 kilograms and 2.5 kilograms, respectively, for placebo. Maximum tolerated volume in the stomach (a measure of satiation) was a median of 750 mL with liraglutide and 1,126 mL with placebo.

The time it took half a meal to empty from the stomach at 5 weeks correlated significantly with change in weight loss at 16 weeks.

About 63% of liraglutide recipients and 19% of placebo recipients experienced nausea, the most commonly reported adverse event.

With liraglutide, Dr. Camilleri noted, "the biggest weight loss occurs in the first three months to four months, and then it stabilizes. What is really very interesting is (that) the time when there seems to be the highest effect on stomach emptying is the time when people have observed the greatest degree of weight loss."

"One way to manage patients given this medication is to get a stomach emptying study after say five or six weeks," he added, "and if the stomach emptying is not delayed, then this patient may not be an ideal candidate for the drug."

Up to a quarter of obese individuals have faster-than-normal gastric emptying, which could make them even better candidates for treatment, Camilleri noted. "Now that we know that this medication slows stomach emptying, perhaps we can identify that a biomarker that predicts greater response to this treatment would be accelerated gastric emptying at baseline," he said.

In an accompanying editorial, Dr. Vincenzo Stanghellini of the University of Bologna in Italy writes, "The main strength of this study is that, unlike previous studies, gastric functions were measured as rigorously as possible using currently available techniques."

The finding that liraglutide's effect on gastric emptying faded over time calls its clinical effectiveness into question, he added, noting that repeated treatments rather than continuous maintenance might result in less tachyphylaxis, as well as lower cost.

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Lancet Gastroenterol Hepatol 2017.