Once-Weekly Subcutaneous Semaglutide 2.4 mg in Adolescents with Overweight or Obesity

Background STEP TEENS (NCT04102189) was the first, phase 3a trial to examine the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg (sema) + lifestyle intervention in adolescents (12 to <18 yrs) with obesity (body mass index [BMI] ≥95th percentile), or overweight (BMI ≥85th percentile) with ≥1 weight-related comorbidity. Methods Participants were randomized 2:1 to sema (n=134) or matching placebo (PBO, n=67). Endpoints (baseline [BL]–wk 68) were %-change in BMI (primary); ≥5% weight loss (WL; confirmatory secondary); and ≥10, ≥15, and ≥20% WL, cardiometabolic risk factors and quality of life (QoL; secondary), assessed by the treatment policy estimand. Primary and confirmatory secondary endpoints were controlled for multiplicity. Results Of 201 adolescents (62.2% female; mean age 15.4 yrs, body weight 107.5 kg, BMI 37.0 kg/m2) randomized, 89.6% completed treatment. Mean change in BMI (BL-wk 68) was –16.1% (sema) 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 sema 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 sema 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 lipid concentrations were reduced with sema (p<0.05). Sema improved overall weight-related QoL (p=0.038) and physical function (p=0.005). Adverse events (AEs) were reported by 78.9% (sema) and 82.1% (PBO) of participants. Serious AEs were reported by 11.3% (sema) and 9.0% (PBO) of participants. More participants reported gastrointestinal AEs with sema (61.7%) vs PBO (41.8%). In each group, 4.5% of participants stopped treatment due to AEs. Conclusions In adolescents with overweight/obesity, sema resulted in significant reductions in BMI, body weight and waist circumference, and cardiometabolic risk factors and QoL improved. Sema was generally well-tolerated with a safety profile consistent with the GLP-1RA class.