麻豆传媒

Liraglutide (Saxenda) was associated with weight loss among children with obesity when added to exercise and nutrition counseling, according to a randomized trial sponsored by the drug's manufacturer.

Among 251 adolescents, those assigned to 3 mg subcutaneous liraglutide daily plus lifestyle therapy had significantly reduced body mass index (BMI) standard-deviation scores at week 56 compared to children who were assigned to lifestyle therapy alone (difference -0.22, 95% CI -0.37 to -0.08, P=0.002), reported Aaron S. Kelly, PhD, of the University of Minnesota in Minneapolis, and colleagues.

Compared to children on placebo, those on liraglutide also experienced a greater relative change in BMI (-4.64 percentage points) and body weight (-4.50 kg), they reported at the virtual ENDO meeting for this year. The findings were simultaneously published online in the . That translated to an average 1.75-point reduction from baseline in participants' BMI.

"The degree of BMI reduction with 3 mg liraglutide in the adolescent trial appears to compare favorably to orlistat, a medication currently approved by the [FDA] for adolescents ages 12 to less than 18 years old," Kelly told 麻豆传媒 in an email, noting that direct comparisons were not possible due to differences in trial designs.

Liraglutide, which works like glucagon-like peptide (GLP-1) receptor proteins in the pancreas to slow digestion, was to treat adults with obesity and at least one weight-related comorbidity.

This adolescent trial was conducted as part of the post-marketing commitments to the FDA and the European Medicines Agency for liraglutide as a weight-loss treatment, Kelly said.

Since the absolute changes in body weight observed in this study were relatively small, it appears that much of liraglutide's benefit stems from preventing weight gain, rather than promoting weight loss, commented William Tamborlane, MD, of Yale University in New Haven, Connecticut, who was not involved with this study.

As such, liraglutide may be most useful as an adjunct to bariatric surgery to prevent weight gain postoperatively, Tamborlane said.

"These kids lost only about 5 pounds from baseline, so while [liraglutide] could be something that is useful, by itself, it's not going to take care of a lot of problems," Tamborlane told 麻豆传媒.

Still, even slight weight loss in adolescence can significantly improve cardiometabolic factors, enhance insulin response, and ultimately slow the development of type 2 diabetes later in life, Tamborlane added.

"If you have an intervention that can prevent continued weight gain, that may be of benefit for adolescents," Tamborlane said.

Liraglutide has appetite-suppressing effects, which may contribute to the gastrointestinal events associated with the drug, Tamborlane noted.

In this study, a significantly higher proportion of participants in the liraglutide group reported gastrointestinal adverse events compared to placebo (64.8% vs 36.5%), leading to discontinuation of treatment for 13 and zero patients, respectively, Kelly and co-authors reported. The most common events were nausea (42.4% vs 14.3%), vomiting (34.4% vs 4%), and diarrhea (22.4% vs 14.3%), which mostly occurred in the dose-escalation period, they added.

Liraglutide was also associated with more hypoglycemic episodes than placebo (26 vs 18), but there were no significant differences in pubertal development or bone age, researchers reported.

Notably, 10.4% and 14.3% of participants in the liraglutide and placebo arms, respectively, reported adverse events related to psychiatric disorders. One patient in the intervention arm died by suicide, and two patients in the control group attempted suicide, they added.

"Although we cannot provide specific details owing to confidentiality, this event was deemed to be unrelated to trial treatment by the site principal investigator," Kelly said. "It should also be noted that current product labeling for liraglutide 3-mg states that patients should be monitored for suicidal ideation [and] mental health."

Study Details, Further Findings

This involved children ages 12-18, who were obese with stable body weights and documented poor response to lifestyle therapy alone. Individuals with type 1 diabetes were excluded.

Conducted at 32 sites in Europe, Mexico, and the U.S, the study had a 12-week run-in period followed by 4-8 weeks of dose escalation and a total treatment period of 56 weeks. The lifestyle therapy assigned to both trial arms involved a combination of nutrition and physical activity counseling.

In total, 101 of 125 (80.8%) adolescents completed the intervention and 100 of 126 (79.4%) children completed the placebo, a volume-matched subcutaneous injection. Upwards of 70% of both cohorts were female, and the average age was about 14.5 across groups. Mean BMI was 35.3 and 35.8 in the liraglutide and placebo arms, respectively.

In addition to the intention-to-treat analysis used for the primary endpoint -- change from baseline in BMI standard-deviation score -- Kelly and colleagues reported a similar treatment effect in a mixed model using repeated measurements for missing variables (-0.26, 95% CI -0.39 to -0.13), they noted.

Moreover, 43.3% of teens receiving the active drug experienced BMI reductions of at least 5% at week 56, compared to 18.7% in the placebo group. BMI reductions of at least 10% were also observed in 26.1% and 8.1% of children in the liraglutide and placebo arms, respectively.

Weight loss appeared to be maintained after treatment discontinuation as well, with teens in the liraglutide group having a greater increase in BMI standard-deviation scores at week 82 compared to placebo (difference 0.15, 95% CI 0.07-0.23), they added.

Notably, there were no differences in cardiometabolic variables or weight-related quality of life observed between treatment groups.

"These results could be due to the fact that most participants had baseline variables within the normal range or could reflect the limited sample size, which was selected on the basis of power calculations relevant to the BMI standard-deviation score," Kelly and colleagues wrote.

In addition to a limited power to detect differences in cardiometabolic markers and quality of life, this study was limited by lack of specific measurements of body composition, the authors acknowledged.

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