JAMA Pediatr:GLP-1受体激动剂抗青少年重度肥胖

　　美国明尼苏达大学的Kelly等2月4日在线发表于《美国医学会杂志•儿科学》（JAMA Pediatr）的一项初步研究结果表明，胰高血糖素样肽1（GLP-1）受体激动剂用于治疗青少年重度肥胖可行、安全和有效。

he Effect of Glucagon-Like Peptide-1 Receptor Agonist Therapy on Body Mass Index in Adolescents With Severe Obesity

A Randomized, Placebo-Controlled, Clinical Trial 

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.