Adjunct liraglutide therapy helps lower BMI in obese teens
Adding liraglutide to first-line lifestyle therapy led to a significantly reduced BMI standard-deviation score (BMI SDS*) among obese adolescents who failed to respond to lifestyle therapy alone, according to a study presented at ENDO 2020.
“Obesity is a chronic disease with limited treatment options in paediatric patients … and lifestyle therapy, the typical first treatment, often yields suboptimal responses, ... [Using] liraglutide [as adjunct therapy] may be useful for weight management in adolescents with obesity,” said lead author Professor Aaron Kelly from the Department of Pediatrics and co-director of the Center for Pediatric Obesity Medicine at the University of Minnesota Medical School in Minneapolis, Minnesota, US.
The phase III, double-blind trial involved 251 adolescents with obesity (aged 12 to <18 years, 40.6 percent male, mean BMI 35.6 kg/m2, mean BMI SDS 3.17) who reported a poor response from a 12-week run-in period of lifestyle therapy, which involved healthy nutrition counselling and physical activity for weight loss. Participants were randomized in 1:1 ratio to receive either subcutaneous liraglutide 3.0 mg (n=125) or placebo (n=126) once/day for a 56-week treatment period, in addition to lifestyle therapy, and then a 26-week follow-up period of no treatment. The primary endpoint of the study was the change from baseline in the BMI SDS score at 56 weeks. [ENDO 2020, abstract OR33-01; N Engl J Med 2020;doi:10.1056/NEJMoa1916038]
At 56 weeks, liraglutide-treated patients had a significantly greater reduction in the BMI SDS from baseline compared with placebo-treated patients (estimated treatment difference [ETD], -0.22; p=0.002), which the researchers considered to be clinically meaningful.
Significantly more patients who received liraglutide experienced a BMI reduction of ≥5 percent (43.3 percent vs 18.7 percent; p=0.0002) and ≥10 percent from baseline (26.1 percent vs 8.1 percent; p=0.0006) than those who had placebo.
Patients in the liraglutide arm also achieved a greater reduction in body weight (ETD, -4.50 kg and -5.01 percentage points for absolute and relative changes, respectively) and waist circumference (ETD, -2.93 cm) vs the placebo arm.
However, a greater increase in BMI SDS was observed among liraglutide recipients who discontinued treatment from week 56 to 82 compared with placebo recipients (0.22 vs 0.07; ETD, 0.15). “[This weight regain reinforced] the concept that obesity is a chronic disease that requires continued treatment,” the researchers noted.
Gastrointestinal-related adverse events, such as nausea, vomiting, and diarrhoea, occurred more frequently in the liraglutide arm than the placebo arm (64.8 percent vs 36.5 percent; p<0.001), of whom 13 and 10 patients discontinued treatment, respectively. “[This] finding suggests [that] liraglutide may not be suitable for all patients,” the researchers highlighted.
“Although evidence in children is limited, [our results showed a greater ETD of -0.22] than [the treatment] differences observed in trials of lifestyle therapy conducted by the US Preventive Services Task Force (-0.17) and in an overview of six Cochrane reviews (-0.13),” the researchers said.
“This trial demonstrates clinically meaningful weight loss in adolescents with obesity treated with liraglutide 3.0 mg as an adjunct to lifestyle therapy,” Kelly concluded, who added that “we need additional treatment options that we can use along with lifestyle therapy”.
*BMI SDS: Measure of the number of standard deviations from the population mean BMI, matched for age and sex