Local teens with obesity see dramatic weight loss in UB clinical trial

For teens who have struggled with obesity, it probably sounded too good to be true: a weekly injection that could help them control their eating and lead to weight loss. But the results of the clinical trial on the drug semaglutide, released online ahead of print Nov. 3 in the New England Journal of Medicine and presented at Obesity Week, the discipline’s major conference, turned out to be better than anything the participants — or even the researchers — expected.

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% versus .6% with the placebo — results providers responded to with surprise and enthusiasm, and national media described as “mind-blowing” and “stunning.”

UB researchers 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 Mastrandrea, a co-author on the NEJM study and chief of the Division of Pediatric Endocrinology in the Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences at UB.

“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 notes. “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 approved by the FDA 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 that showed that liraglutide, another GLP agonist, produced weight loss in children and adolescents.

The success of the UB 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 explains. 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.”

Five Western New York teens aged 13-17 were recruited and four completed the trial. “We had a tremendous retention rate, both here in Buffalo and nationwide,” Mastrandrea says. “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% of their body weight; in the overall trial, 73% of study participants treated with semaglutide lost at least 5% 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 participate in moderate activity at least five times a week and to follow healthy eating habits.

Mastrandrea thinks the results 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 sees patients at UBMD Pediatrics; her practice is affiliated with the Healthy Weigh clinic at John R. Oishei Children’s Hospital.

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