Semaglutide triumphs as an anti-obesity treatment for adolescents
Adding a once-weekly dose of semaglutide to lifestyle intervention successfully reduced body mass index (BMI) in adolescents with obesity, according to results of the phase IIIa STEP TEENS trial.
This multinational, double-blind trial involved 201 adolescents (age 12 to <18 years; mean age 15.4 years, 62 percent female, 79 percent White) with overweight (BMI ≥85th percentile and ≥1 weight-related comorbidity) or obesity (BMI ≥95th percentile). After a 12-week lifestyle intervention regimen, they were randomized 2:1 to receive subcutaneous semaglutide (2.4 mg [dose escalation over 16 weeks starting at 0.25 mg to 2.4 mg or maximal tolerated dose]) or placebo once a week for 68 weeks plus lifestyle intervention.
Patients who had experienced weight change of >5 kg or used anti-obesity medications within 90 days pre-screening, those with uncontrolled thyroid disease, and those who had previously undergone bariatric surgery were among those excluded. Ninety percent of patients completed the trial. Mean BMI was 37 kg/m2, waist circumference 110.4 cm, and HbA1c 5.5 percent. Four percent of patients had type 2 diabetes and 13 percent hypertension.
At week 68, there was a greater reduction in BMI from baseline in patients assigned to semaglutide than placebo (mean change –16.1 percent vs 0.6 percent; estimated difference, −16.7 percentage points, 95 percent confidence interval [CI], −20.3 to −13.2; p<0.001). [N Engl J Med 2022;doi:10.1056/NEJMoa2208601]
Significantly more patients in the semaglutide than placebo group experienced a ≥5-percent reduction in body weight by week 68 (73 percent vs 18 percent; estimated odds ratio, 14.0, 95 percent CI, 6.3–31.0; p<0.001).
A ≥5-percent reduction in BMI occurred in more patients in the semaglutide than placebo group (76 percent vs 23 percent), as did weight loss of ≥10, ≥15, and ≥20 percent (62 percent vs 8 percent, 53 percent vs 5 percent, and 37 percent vs 3 percent, respectively).
At week 68, patients in the semaglutide group also experienced a greater reduction in waist circumference than those in the placebo group (–12.7 vs –0.6 cm), as well as HbA1c (–0.4 vs –0.1 percentage points), total cholesterol (–8.3 percent vs –1.3 percent), LDL cholesterol (–10.2 percent vs –3.4 percent), VLDL cholesterol (–28.4 percent vs 1.6 percent), triglyceride (–28.4 percent vs 2.6 percent), and alanine aminotransferase levels (–18.3 percent vs –4.9 percent). However, the changes in blood pressure and HDL cholesterol levels from baseline to week 68 did not significantly differ between groups. Semaglutide was associated with improved quality of life over placebo, as determined by Impact of Weight on Quality of Life–Kids total score, particularly the physical comfort domain score.
Adverse event (AE) rates were higher among semaglutide than placebo recipients (435.7 vs 362.9 events per 100 person-years), with AEs reported in 79 and 82 percent, respectively. The most common AEs were gastrointestinal which occurred more often in semaglutide than placebo recipients (62 percent vs 42 percent) and were generally of mild to moderate severity. Cholelithiasis was documented in five semaglutide and no placebo recipients. Serious AEs occurred in 11 and 9 percent of semaglutide and placebo recipients, respectively, and there were no fatal AEs. Five percent of patients in each group discontinued treatment due to AEs. Psychiatric AEs were reported in 7 percent vs 15 percent. There were no incidents of pancreatitis, acute renal failure, diabetic retinopathy, or severe hypoglycaemia.
“The safety of semaglutide in this adolescent population appeared to be consistent with findings among adults with overweight or obesity,” the researchers said.
The improvement in cardiometabolic risk factors with semaglutide is particularly important seeing as how these factors are associated with cardiovascular outcomes in adulthood, they highlighted.
The researchers noted that the relatively short follow-up period prevented ascertainment of the durability of the benefit of semaglutide as well as any effect of treatment cessation. The population was also primarily female and White which may have limited the generalizability of the findings.