Prescribing liraglutide plus lifestyle therapy for adolescents with obesity resulted in greater weight loss and greater reduction in body mass index, compared with those prescribed lifestyle therapy alone, according to findings from a new study published in The New England Journal of Medicine.
Liraglutide with lifestyle therapy also “compared favorably in terms of [body mass index] reduction,” compared with other pediatric weight-management programs in the United States and with use of orlistat, wrote Aaron S. Kelly, PhD, of the University of Minnesota, Minneapolis, and colleagues. The study abstract was presented during a virtual news conference held by The Endocrine Society. It had been slated for presentation during ENDO 2020, the society’s annual meeting, which was canceled because of the COVID-19 pandemic.
The study included adolescents aged 12-17 years, who had obesity (BMI, ≥30 kg/m2) and had responded poorly to recommendations involving lifestyle therapy only, as judged by the site investigator and documented in the participant’s medical records. The adolescents participated at one of five sites in Belgium, Mexico, Russia, Sweden, and the United States.
In the randomized, controlled, double-blind trial, 125 participants received 3 mg liraglutide, and 126 received placebo for 56 weeks, during which both groups received lifestyle therapy, “defined as counseling about healthy nutrition and physical activity for weight loss,” the authors wrote.
After 12-weeks of run-in, the treatment period lasted 56 weeks, with a follow-up 26 weeks after treatment ended. The liraglutide group retained 80.8% of its participants, and the placebo group, 79.4%.
At week 56, there were no significant differences between the groups in blood pressure, fasting lipids, fasting plasma glucose, or hemoglobin A1c, the authors noted.
However, in the liraglutide group, 43.3% of participants lost at least 5% of their BMI, compared with 18.7% in the control group. Similarly, 26.1% of those in the liraglutide group had a BMI reduction of at least 10%, compared with 8.1% in the control group.
Participants in the liraglutide group also saw a greater reduction in BMI, compared with those in the placebo group (estimated difference, 4.64 percentage points), and those taking liraglutide lost 9.9 pounds (4.5 kg) more than those receiving placebo – a relative reduction of 5%. The authors noted that a weight loss of 3%-5% “significantly improves some health-related outcomes in adults.”
In addition, the liraglutide group had a BMI standard-deviation score that was 0.22 lower than that in the placebo group (P = .002), but after the participants discontinued with the trial, “a greater increase in the BMI standard-deviation score was observed with liraglutide than with placebo (0.15),” the authors reported.
“Although evidence in children is limited, a change in BMI standard-deviation score of at least 0.20 has been suggested to be clinically meaningful,” they wrote. “Some studies indicate that even temporary weight loss may have long-term benefits, but the extent to which this applies in adolescents and the extent to which long-term adherence to pharmacotherapy can be expected are unknown.”
The researchers added that the reduction in standard-deviation score seen in this study, of 0.22, was a bigger reduction than that seen in lifestyle therapy trials from the U.S. Preventive Services Task Force and from an overview of six Cochrane reviews. Their trial also, however, had a fairly high adherence rate, over 80%.
No notable differences in cardiometabolic markers or in quality of life showed up between the liraglutide and placebo groups. The heterogeneous treatment response in this and past studies suggests the need for future trials to “characterize predictors of treatment response to identify patients who would benefit the most from treatment,” the authors wrote.
About twice as many participants taking liraglutide experienced gastrointestinal adverse events compared with those receiving placebo (64.8% vs. 36.5%, respectively). Those symptoms, a known side effect of this drug type, included nausea, vomiting, and diarrhea and occurred primarily during escalation of the drug dose before then dropping in frequency. Still, the authors note that the high rate of gastrointestinal effects “suggests that this treatment may not be suitable for all patients.”
None of the adolescents receiving the placebo stopped treatment, but 10.4% of those taking liraglutide discontinued. One participant in the liraglutide group died by suicide, but the death was determined to be unrelated to the therapy.
Although the 0.22 reduction in the BMI standard-deviation score was for the intent-to-treat population, the authors calculated that the difference would have been 0.26 “if all participants had adhered to the treatment throughout the trial.”
Novo Nordisk funded the research. Several of the authors reported that they are employees of the company.
The abstract will also be published in a special supplemental issue of the Journal of the Endocrine Society. In addition to a series of news conferences on March 30-31, the society will ost ENDO Online 2020 during June 8-22, which will present programming for clinicians and researchers.
Source: Kelly AS et al. NEJM. 2020 Mar 31. doi: 10.1056/NEJMoa1916038.