Background: STEP TEENS (NCT04102189) was the first phase 3a trial to examine the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg + lifestyle intervention in adolescents (12 to < 18 years) with obesity (body mass index [BMI] ≥95th percentile), or overweight (BMI ≥85th percentile) with ≥1 weight-related comorbidity.
METHODS AND RESULTS: Participants were randomized 2:1 to semaglutide (n=134) or matching placebo (PBO; n=67). Endpoints (baseline [BL]–wk 68) were percentage (%) change in BMI (primary); ≥5% weight loss (WL; confirmatory secondary); and ≥10, ≥15, and ≥20% WL, change in cardiometabolic risk factors and quality of life (QoL; secondary), assessed by the treatment policy estimand. Primary and confirmatory secondary endpoints were controlled for multiplicity. Of 201 adolescents (62.2% female; mean age 15.4 years, body weight 107.5 kg, BMI 37.0kg/m2) randomized, 89.6% completed treatment. Mean change in BMI (BL–wk 68) was –16.1% (semaglutide) vs 0.6% (PBO; estimated treatment difference [ETD]: –16.7%-points; 95% CI: −20.3, −13.2; p< 0.0001). ETD in body weight %-change (BL–wk 68) for semaglutide vs PBO was –17.4%-points (95% CI: –21.1, –13.7; p< 0.0001). More participants achieved ≥5, ≥10, ≥15, and ≥20% WL with semaglutide vs PBO (72.5 vs 17.7%, 61.8 vs 8.1%, 53.4 vs 4.8%, 37.4 vs 3.2%; p< 0.0001). Waist circumference, HbA1c, and lipids (except high-density lipoprotein) were reduced with semaglutide (p < 0.05). Semaglutide improved overall weight-related QoL (p=0.038) and physical comfort (p=0.005). Adverse events (AEs) were reported by 78.9% (semaglutide) and 82.1% (PBO) of participants. Serious AEs were reported by 11.3% (semaglutide) and 9.0% (PBO) of participants. More participants reported gastrointestinal AEs with semaglutide (61.7%) vs PBO (41.8%). In each group, 4.5% of participants stopped treatment due to AEs.
Conclusion: In adolescents with overweight/obesity, semaglutide resulted in significant reductions in BMI, body weight and waist circumference, and improvements in cardiometabolic risk factors and QoL. Semaglutide was generally well tolerated with a safety profile consistent with the GLP-1RA class.