The effect of glucagon-like peptide-1 receptor agonist therapy on body mass index in adolescents with severe obesity: a randomized, placebo-controlled, clinical trial.

Abstract

IMPORTANCE:

Medical treatment options for pediatric obesity remain limited. Glucagon-like peptide-1 (GLP-1) receptor agonists induce weight loss by suppressing appetite and increasing satiety, but few studies have evaluated this therapy as a treatment for obesity.

OBJECTIVE:

To evaluate the effects of exenatide on body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and cardiometabolic risk factors in adolescents with severe obesity.

DESIGN:

Three-month, randomized, double-blind, placebo-controlled, multicenter clinical trial followed by a 3-month open-label extension.

SETTING:

An academic medical center and an outpatient pediatric endocrinology clinic.

PATIENTS:

A total of 26 adolescents (12-19 years of age) with severe obesity (BMI ≥ 1.2 times the 95th percentile or BMI ≥ 35).

INTERVENTION:

All patients received lifestyle modification counseling and were equally randomized to exenatide or placebo injection, twice per day.

MAIN OUTCOME MEASURES:

The primary end point was the mean percent change in BMI measured at baseline and 3 months. Secondary end points included absolute change in BMI, body weight, body fat, blood pressure, hemoglobin A1c, fasting glucose, fasting insulin, and lipids at 3 months.

RESULTS:

Twenty-two patients completed the trial. Exenatide elicited a greater reduction in percent change in BMI compared with placebo (-2.70% [95% CI, -5.02% to -0.37%]; P = .03). Similar findings were observed for absolute change in BMI (-1.13 [95% CI, -2.03 to -0.24]; P = .02) and body weight (-3.26 kg [95% CI, -5.87 to -0.66 kg]; P = .02). Although not reaching the level of statistical significance, reduction in systolic blood pressure was observed with exenatide. During the open-label extension, BMI was further reduced in those initially randomized to exenatide (cumulative BMI reduction of 4%).

CONCLUSIONS AND RELEVANCE:

These results provide preliminary evidence supporting the feasibility, safety, and efficacy of GLP-1 receptor agonist therapy for the treatment of severe obesity in adolescents.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT01237197.

• Authors: Aaron S Kelly, Kyle D Rudser, Brandon M Nathan, Claudia K Fox, Andrea M Metzig, Brandon J Coombes, Angela K Fitch, Eric M Bomberg, M Jennifer Abuzzahab
• Journal: JAMA pediatrics (JAMA Pediatr) Vol. 167 Issue 4 Pg. 355-60 (Apr 2013) ISSN: 2168-6211 [Electronic] United States
• PMID: 23380890 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• GLP1R protein, human
• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Peptides
• Receptors, Glucagon
• Venoms
• Glucagon-Like Peptide 1
• Exenatide

Topics

• Adolescent
• Body Constitution (drug effects)
• Body Mass Index
• Double-Blind Method
• Exenatide
• Female
• Glucagon-Like Peptide 1 (agonists)
• Glucagon-Like Peptide-1 Receptor
• Humans
• Hypoglycemic Agents (pharmacology)
• Male
• Peptides (pharmacology)
• Receptors, Glucagon (agonists)
• Satiety Response (drug effects)
• Venoms (pharmacology)