By Ellen Goldbaum

Participants who received the weekly injection of the glucagon-like peptide-1 (GLP) receptor agonist semaglutide saw an average reduction in their percent body mass index (BMI) of 16.1 percent versus .6 percent with the placebo, results providers responded to with surprise and enthusiasm, and which national media described as “mind-blowing” and “stunning.”

Researchers at the Jacobs School of Medicine and Biomedical Sciences who worked on the study chose more reserved language to describe the results, but they were equally impressed.

“I knew that it was an effective weight loss drug because of what we learned from its use in adult patients,” says Lucy D. Mastrandrea, MD, PhD, a co-author on the NEJM study, associate professor of pediatrics and chief of its Division of Endocrinology/Diabetes. 

“Still, the weight loss we saw from the combination of this drug and lifestyle changes was so dramatic it was almost a bit unnerving," she says. “This work is moving the field of obesity management forward in pediatric patients and we are doing it here in Buffalo.”

Mastrandrea, who sees patients through UBMD Pediatrics, has led previous national studies on other drugs that have since been FDA approved to help children and adolescents with Type 1 and Type 2 diabetes achieve better blood sugar control. She also led the study that resulted in another NEJM publication in 2020, which showed that liraglutide, another GLP agonist, produced weight loss in children and adolescents. 

The success of the Jacobs School researchers in recruiting and retaining participants in that trial led to Mastrandrea’s participation in the semaglutide trial with teens.

“We were one of the top academic medicine groups in the semaglutide study to recruit and retain subjects,” she says.

In total, the study included 37 sites nationwide with 229 participants.

“Our success in recruiting and retaining participants is because of the experienced UBMD Pediatrics research team,” she adds.

Five Western New York teens ages 13-17 were recruited and four completed the trial.

“We had a tremendous retention rate, both here in Buffalo and nationwide,” Mastrandrea adds. “These teens stayed with it because they saw results.”

During the year when the study was being conducted, of the four patients in Buffalo who were randomized to receive the drug, all lost at least 5 percent of their body weight; in the overall trial, 73 percent of study participants treated with semaglutide lost at least 5 percent of their body weight.

“These were people who had worked hard, some of them for years, to try and manage their weight with just diet and exercise, which are the primary tools we have had,” Mastrandrea says. 

“We typically say ‘try to lose a pound or two a week,’ so when patients were losing as much as 20 pounds after 6-8 weeks, that was huge,” she says. “Patients were really happy. They were saying things like, ‘It was so hard before and now it’s working. I feel better about myself. I’m buying new clothes.’”

The participants also exhibited improved levels of triglycerides and other cardiometabolic measures, as well as improved quality of life measures.

While the previous study with liraglutide, another drug in the same class, also resulted in significant weight loss for teens, the semaglutide results were dramatic, according to Mastrandrea.

“We didn’t compare the two drugs, but in a similar aged population with a similar degree of obesity, this study really demonstrated a better response in terms of weight loss,” she says.

Semaglutide acts by binding to the glucagon like peptide receptor, which delays gastric emptying.

“We think that mechanism feeds back to the brain’s appetite centers in the hypothalamus so the person doesn’t feel so hungry,” Mastrandrea explains.

The study included a 12-week lifestyle intervention period that required participants to take part in moderate activity at least five times a week and to follow healthy eating habits. 

Mastrandrea thinks the results that participants saw from the drug may have positively influenced their level of participation in the lifestyle intervention, resulting in further weight loss.

“I do think that as people see success with losing weight, they start altering their behaviors,” she says. “They may feel more comfortable with incorporating exercise into their lives in a more consistent manner, so the drug might have positively impacted their healthy behaviors.”

Mastrandrea’s practice is affiliated with the Healthy Weigh clinic at Oishei Children’s Hospital. 

The study was funded by Novo Nordisk, which produces semaglutide.