title: Exenatide as a weight-loss therapy in extreme pediatric obesity: a randomized, controlled pilot study.
abstract: The objective of this pilot study was to evaluate the effects of exenatide on BMI (primary endpoint) and cardiometabolic risk factors in nondiabetic youth with extreme obesity. Twelve children and adolescents (age 9-16 years old) with extreme obesity (BMI ≥1.2 times the 95th percentile or BMI ≥35 kg/m(2)) were enrolled in a 6-month, randomized, open-label, crossover, clinical trial consisting of two, 3-month phases: (i) a control phase of lifestyle modification and (ii) a drug phase of lifestyle modification plus exenatide. Participants were equally randomized to phase-order (i.e., starting with control or drug therapy) then crossed-over to the other treatment. BMI, body fat percentage, blood pressure, lipids, oral glucose tolerance tests (OGTT), adipokines, plasma biomarkers of endothelial activation, and endothelial function were assessed at baseline, 3-, and 6-months. The mean change over each 3-month phase was compared between treatments. Compared to control, exenatide significantly reduced BMI (-1.7 kg/m(2), 95% confidence interval (CI) (-3.0, -0.4), P = 0.01), body weight (-3.9 kg, 95% CI (-7.11, -0.69), P = 0.02), and fasting insulin (-7.5 mU/l, 95% CI (-13.71, -1.37), P = 0.02). Significant improvements were observed for OGTT-derived insulin sensitivity (P = 0.02) and β-cell function (P = 0.03). Compliance with the injection regimen was excellent (≥94%) and exenatide was generally well-tolerated (the most common adverse event was mild nausea in 36%). These preliminary data suggest that exenatide should be evaluated in larger, well-controlled trials for its ability to reduce BMI and improve cardiometabolic risk factors in youth with extreme obesity.
authors.affiliation: Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA. kelly105@umn.edu
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Kelly
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Metzig
authors.forename: Kyle D
authors.initials: KD
authors.lastname: Rudser
authors.forename: Angela K
authors.initials: AK
authors.lastname: Fitch
authors.forename: Claudia K
authors.initials: CK
authors.lastname: Fox
authors.forename: Brandon M
authors.initials: BM
authors.lastname: Nathan
authors.forename: Mary M
authors.initials: MM
authors.lastname: Deering
authors.forename: Betsy L
authors.initials: BL
authors.lastname: Schwartz
authors.forename: M Jennifer
authors.initials: MJ
authors.lastname: Abuzzahab
authors.forename: Laura M
authors.initials: LM
authors.lastname: Gandrud
authors.forename: Antoinette
authors.initials: A
authors.lastname: Moran
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Billington
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Schwarzenberg
mesh_terms: D000293:Adolescent; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control*; D002648:Child; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000517:prevention & control; D000077270:Exenatide; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008910:Minnesota / Q000453:epidemiology; D009767:Obesity, Morbid / Q000188:drug therapy* / Q000453:epidemiology; D010455:Peptides / Q000494:pharmacology / Q000627:therapeutic use*; D010865:Pilot Projects; D012307:Risk Factors; D040242:Risk Reduction Behavior; D013997:Time Factors; D016896:Treatment Outcome; D014688:Venoms / Q000494:pharmacology / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D010455:Peptides; D014688:Venoms; D000077270:Exenatide
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