Benefits of GLP-1 Receptor Agonists in Teens

Researchers have identified factors that may predict which adolescents may experience the most weight loss benefit from the use of glucagon-like peptide (GLP)-1 receptor agonists.

A small pooled data study, published recently in Clinical Obesity, found that female sex and an increased appetite at baseline were both significant predictors of which adolescents experienced the greatest change in body mass index (BMI) after 3 months of treatment with the GLP-1 agonist exenatide.

“Importantly, these are characteristics that can be measured easily in the clinical setting and therefore be potentially clinically useful,” wrote researcher Brandon M. Nathan, MD, of the Department of Pediatrics at the University of Minnesota Masonic Children’s Hospital, and colleagues. “The results of the current study should be tested in a larger and longer clinical trial designed to evaluate predictors of weight loss responsiveness to GLP-1 receptor agonist treatment and to determine whether other characteristics or additive combinations may further define the most responsive populations.”

Nathan and colleagues had previously published results from two clinical trials that evaluated the use of exenatide in adolescents with severe obesity. Patients in these studies assigned to exenatide had 3% to 5% reductions in BMI compared with patients assigned placebo. However, the researchers noted variability in the magnitude of weight loss response among study participants.

Therefore, they performed a pooled data analysis of the two trials to evaluate possible factors that may have influenced which patients benefited most from use of exenatide. The analysis included data from 32 patients with a mean age of 14.3 and a mean BMI of 39.8. Patients had been assigned to exenatide 5 mcg twice daily for the first month and then 10 mcg twice daily for 2 months.

The researchers found a pooled data treatment effect on BMI at 3 months of -3.42% for exenatide compared with placebo.

Looking at only those patients assigned to exenatide, the researchers found that those patients with a high self-reported baseline appetite had significantly more benefit from the drug at 3 months than did those with a low self-reported baseline appetite (-4.28% vs. 1.02%; P=0.028).

“The proposed mechanisms for weight loss with GLP-1 receptor agonists are thought to be through alterations in hypothalamic centres for appetite and satiety combined with a slowing of gastric motility that induces a greater sense of fullness. It is therefore not completely unexpected that individuals with higher baseline levels of appetite responded better than those who did not,” the researchers wrote.

In addition, female patients also had significantly more benefit from treatment at 3 months as compared with male patients (-4.78% vs. 0.76%; P=0.007). According to the researchers, it could be hypothesized that this difference could be an effect of “other hormones known to be different between sexes such as leptin.”

No association between change in BMI at 3 months and baseline BMI, BMI percent change at 1 month, age, incidence of nausea, vomiting or other gastrointestinal symptoms, and satiety scores were found.

“Limitations of the study include the relatively small sample size, short duration of treatment, the fact that the analysis was secondary and post hoc in nature and that the population enrolled were predominantly white with a greater proportion of female participants,” the researchers wrote. “As such, results should be viewed as hypothesis-generating.”

Nathan BM, et al. Predictors of weight-loss response with glucagon-like peptide-1 receptor agonist treatment among adolescents with severe obesity. Clin Obes. Epub 2015 Dec 18.