1. The combination of liraglutide and lifestyle therapy was shown to significantly reduce body mass index (BMI) standard-deviation score compared to the placebo group.
2. The use of liraglutide as adjuvant therapy was shown to cause a higher frequency of gastrointestinal adverse events.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Obesity is a chronic and progressive disease with few treatment options for the pediatric patient population. The first-line treatment is lifestyle therapy, which has yielded poor results, and bariatric surgery is seldom performed within this patient population. Pharmacologically, only orlistat and phentermine have been approved by the Food and Drug Administration. As such, liraglutide presents another treatment option in combination with lifestyle therapy for adolescents where obesity is of concern. The study evaluated the efficacy and safety of subcutaneous liraglutide in combination with lifestyle therapy for weight management in adolescents with obesity. All participants received lifestyle therapy and were randomized to receive liraglutide or placebo. The study found the addition of liraglutide with lifestyle therapy led to a greater reduction in the BMI standard-deviation score, a relative measure of BMI adjusted for age and sex, compared to the placebo group. However, the participants in the liraglutide group presented with a higher frequency of gastrointestinal adverse effects compared to the placebo group.
This randomized, double-blind, phase 3, trial was limited by the lack of cardiometabolic profiling conducted throughout the study as secondary outcomes. Since a major concern of childhood obesity surrounds cardiovascular outcomes, cardiometabolic profiling may have elucidated the effect of liraglutide treatment on cardiac health. Nonetheless, this study was strengthened by the high retention rate and evenly matched sample size. For physicians, these findings highlighted an alternative therapy to be prescribed to pediatric patients to complement the weight management through lifestyle therapy.
In-Depth [randomized controlled trial]: This randomized control trial enrolled 251 patients in a multicenter study from 32 sites in five countries. The study population included pubertal adolescents (12 to <18 years of age). Inclusion criteria included: obesity defined as the BMI corresponding to the adult value of 30 or more and in the 95th or higher percentile for age and sex, stable body weight during the 90 days before screening, and poor response to lifestyle therapy alone. The exclusion criteria for the study included adolescents diagnosed with type 1 diabetes. The patients were randomized to the liraglutide treatment or volume-matched placebo treatment in a 1:1 ratio. The primary outcome of the study was the drug efficacy measured by the change of BMI standard-deviation score, from baseline, at week 56 and overall drug safety determined by adverse outcomes. Additionally, the secondary outcome included BMI standard-deviation score from week 56 to week 82 when all pharmacological treatments stopped. The study hypothesized liraglutide treatment adjuvant to lifestyle therapy would result in a greater reduction to the BMI standard-deviation score compared to the placebo group. For drug efficacy, adolescents in the liraglutide group experienced a reduction in the BMI standard-deviation score compared to the placebo group with an estimated treatment difference of -0.22 (95% confidence interval [CI], −0.37 to -0.08) and absolute weight change of -4.5kg (95%CI, -7.17 to -1.84). A greater frequency of adverse effects were reported in the liraglutide group including nausea and vomiting followed by nasopharyngitis, headache, and diarrhea. The secondary outcome of the BMI standard-deviation score after treatment discontinuation indicated a greater increase in the score with liraglutide compared placebo (0.15, 95% CI, 0.07 to 0.23). Taken together, the study concluded efficacy with liraglutide as an adjuvant to lifestyle therapy and a safety profile of increased gastrointestinal events focused around nausea and vomiting.
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