Clinical Trials Sought to Test GLP1-RA, Which May Promote Weight Loss

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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GLP1-RA | Prader-Willi Syndrome News | illustration of researcher at microscope

A class of medications called GLP-1 receptor agonists (GLP1-RA) may help reduce appetite and promote weight loss for people with Prader-Willi syndrome (PWS), according to a review paper.

The paper’s authors called for clinical trials to test these medicines in people with PWS.

Their paper, “The effects of glucagon-like peptide (GLP)-1 receptor agonists on weight and glycaemic control in Prader-Willi syndrome: A systematic review,” was published in the journal Clinical Endocrinology.

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GLP-1 (glucagon-like peptide-1) is a signaling molecule that the gut releases when people eat food. By binding to a specific protein receptor, GLP-1 helps prompt the body to get ready to absorb nutrients and helps to induce a feeling of satiety or fullness after meals.

GLP1-RA are a class of medications that bind to the GLP-1 receptor and mimic the effects of this signaling molecule. In the last two decades, several GLP1-RAs have been approved for use in treating type 2 diabetes.

Here, a team of scientists in Singapore reviewed the published scientific literature on the use of GLP1-RA in people with PWS, which is commonly characterized by hyperphagia (excessive eating) and obesity.

“While the role of GLP-1 in the pathophysiology [development] of obesity or hyperphagia in PWS has not been conclusively demonstrated, its anorexigenic [appetite-suppressing] effect would theoretically make GLP1-RA a potential therapeutic strategy for achieving appetite suppression in PWS patients,” the researchers wrote.

The review covered 10 studies. In total, these studies reported on 23 people with PWS, ages 13 to 37, who were treated with GLP1-RA (specifically either exenatide or liraglutide).

The treatment’s duration ranged from 14 weeks (about 3.5 months) to four years. Of the 23 patients, 16 had type 2 diabetes before starting treatment with GLP1-RA.

Among 14 patients with available data, treatment with GLP1-RA led to a marked decrease in body mass index (BMI), from 1.5 to 16.0 kilograms per square meter (kg/m2), in 10 individuals. BMI is a ratio of weight to height; a high BMI is a marker of obesity.

For 19 of the 23 patients, treatment with GLP1-RA led to decreases in levels of glycated hemoglobin (HbA1c), a marker of high blood sugar. The magnitude of the decrease ranged from 0.3% to 7.5%.

There was no apparent difference in effect on HbA1c or BMI among the different GLP1-RAs, nor was there an apparent connection between these clinical improvements and the duration of treatment.

All five studies that assessed appetite indicated that GLP1-RA treatment reduced patients’ hunger.

GLP1-RA treatment was generally well-tolerated, with no serious side effects reported. The most common side effect of treatment was temporary nausea, which occurred in two cases.

“The limited data to date suggest that GLP1-RA may be a promising strategy for weight, glycaemic [blood sugar] and appetite control in PWS patients, at least in the short term, with no major adverse effects,” the researchers concluded.

The team said that it hopes this review will encourage scientists to conduct clinical trials to test GLP1-RA as a therapy to help manage PWS.

“Medications that have been successfully used for the treatment of simple obesity and T2DM [type 2 diabetes] will need to be studied specifically in the PWS population, with guidance and adjustments made according to the unique PWS phenotype [disease features]. Until further large clinical trials are done to show a definite benefit of GLP1-RA in PWS patients, this cannot at present be recommended as the standard of care,” the researchers wrote.

“We eagerly anticipate the results of large randomized controlled clinical trials in this area, and hope that the findings of this systematic review would encourage more of such trials in various age groups of PWS patients,” they concluded.