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.