Semaglutide is a glucagon-like peptide-1 analog that can reduce hunger, thus supporting weight loss. In a recent New England Journal of Medicine study, researchers report that a weekly dose of semaglutide led to a significant body mass index (BMI) reduction in adolescents.
Study: Once-Weekly Semaglutide in Adolescents with Obesity. Image Credit: SKT Studio / Shutterstock.com
Obesity in young children
By the year 2030, researchers have predicted that over 250 million children and adolescents will be considered obese. Obese children and adolescents are at a greater risk of numerous health conditions, some of which include dysglycemia, high blood pressure, nonalcoholic fatty liver disease, obstructive sleep apnea, dyslipidemia, altered mental health, and reduced quality of life.
Although certain lifestyle changes can improve the quality of life in young obese individuals, their effects are often limited in their ability to significantly reduce BMI values. As a result, several pharmacological agents have been approved to support long-term weight maintenance, some of which include liraglutide, orlistat, and phentermine-topiramate.
About the semaglutide clinical trial
The Semaglutide Treatment Effect in People with Obesity (STEP) TEENS trial is a double-blind, parallel-group, randomized, placebo-controlled trial that included a total of 201 obese or overweight participants between the ages of 12 to 18.
Whereas obesity was defined as a BMI value in the 95th percentile or higher, an individual was considered overweight with a BMI in the 85th percentile or greater. All participants were also diagnosed with at least one weight-related comorbidity.
Each study participant was randomly assigned to receive either a once-weekly 2.4 milligram (mg) dose of semaglutide or placebo that was administered subcutaneously for a total of 68 weeks. In addition to the placebo or drug, all study participants also entered a 12-week lifestyle intervention that involved counseling about healthy diet options and physical activities that could support weight loss.
Any individual who lost more than five kilograms (kg) or used an obesity-related medication within 90 days before the screening was excluded from the study. Additional exclusion criteria included a previous bariatric surgery, uncontrolled thyroid disease, a previous diagnosis of major depressive disorder within two years of screening for the study, a diagnosis of severe psychiatric disorder or bulimia nervosa, as well a history of a suicide attempt.
Efficacy of semaglutide
Of the 201 individuals included in the study, 134 received semaglutide and 67 received placebo, 132 and 64 of whom completed the full 68-week treatment, respectively. In general, the baseline characteristics between both groups were similar, aside from body weight, BMI, and waist circumference, all of which were higher in the semaglutide group.
The mean age of the study participants was 15.4 years, 62% of whom were female and 79% were White. The mean body weight was 107.5 kg and a mean BMI was 37.0.
By the end of the 68-week period, the semaglutide group exhibited a 16.1% reduction in their BMI values as compared to a 0.6% change in the placebo group. Furthermore, 73% of those who received semaglutide lost at least 5% of their body weight, which is comparable to only 18% of the placebo group.
In addition to BMI, semaglutide treatment was also associated with reduced total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein cholesterol, triglycerides, alanine aminotransferase (ALT), and glycated hemoglobin levels as compared to the placebo. There was no difference between semaglutide and placebo treatments in terms of their effects on blood pressure or high-density lipoprotein (HDL) cholesterol levels.
After the medication was discontinued, the study participants in both groups continued to receive lifestyle interventions for an additional seven weeks. By the end of this period, or week 75, the BMI of semaglutide recipients remained below their baseline value, whereas those who received the placebo had a BMI that exceeded their baseline value.
Safety of semaglutide
Importantly, 79% and 82% of semaglutide and placebo recipients, respectively, experienced an adverse effect from the treatment, with the total number of adverse events greater in the semaglutide group.
The most commonly reported adverse events involved the gastrointestinal (GI) system, with the most frequent symptoms including nausea, vomiting, and diarrhea. Adverse GI events were reported in 62% and 42% of semaglutide and placebo recipients, respectively. Importantly, most of these symptoms were mild or moderate in severity, with a maximum duration of two to three days in the semaglutide group.
Serious side effects were reported in 11% and 9% of semaglutide and placebo recipients, respectively. For example, five semaglutide recipients experienced acute gallbladder disease. Nevertheless, the safety profile of semaglutide appears to be consistent with that of other glucagon-like peptide-1 receptor agonists.
Taken together, the clinical trial results indicate that a weekly 2.4 mg dose of semaglutide, along with lifestyle changes, significantly reduces BMI and other weight-related measurements to a greater extent than lifestyle changes alone.
- Weghuber, D., Barett, T., Barrientos-Perez, M., et al. (2022). Once-Weekly Semaglutide in Adolescents with Obesity. The New England Journal of Medicine. doi:10.1056/NEJMoa2208601.