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 - PubMed (original) (raw)
Randomized Controlled Trial
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
Aaron S Kelly et al. JAMA Pediatr. 2013 Apr.
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.
Figures
Figure 1
CONSORT flow diagram showing the progress of patients throughout the trial.
Figure 2
The percent change in BMI during the randomized, placebo-controlled phase and open label phase of the trial. Lighter lines denote individual trajectories (i.e., individual patients); darker lines denote group trajectories (mean percent change in BMI by group at three- and six-months, with 95% confidence bars).
Comment in
- Clinical trials for adolescent obesity: cooking up an alphabet stew of what to do.
Schwimmer JB. Schwimmer JB. JAMA Pediatr. 2013 Apr;167(4):391-3. doi: 10.1001/jamapediatrics.2013.1661. JAMA Pediatr. 2013. PMID: 23381196 No abstract available.
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References
- Flegal KM, Wei R, Ogden CL, Freedman DS, Johnson CL, Curtin LR. Characterizing extreme values of body mass index-for-age by using the 2000 Centers for Disease Control and Prevention growth charts. Am J Clin Nutr. 2009;90:1314–1320. - PubMed
- Freedman DS, Mei Z, Srinivasan SR, Berenson GS, Dietz WH. Cardiovascular risk factors and excess adiposity among overweight children and adolescents: the Bogalusa Heart Study. J Pediatr. 2007;150:12–17. - PubMed
- Weiss R, Taksali SE, Tamborlane WV, Burgert TS, Savoye M, Caprio S. Predictors of changes in glucose tolerance status in obese youth. Diabetes Care. 2005;28:902–909. - PubMed
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