Oral Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2023

Once-weekly subcutaneous semaglutide 2.4 mg in adolescents with overweight or obesity (97696)

Teresa Girolamo 1 , Daniel Weghuber 2 , Timothy Barrett 3 , Margarita Barrientos-Perez 4 , Inge Gies 5 , Dan Hesse 6 , Ole K Jeppesen 6 , Aaron S Kelly 7 , Lucy D Mastrandrea 8 , Rasmus Sorrig 6 , Silva Arslanian 9
  1. ReYou Health, Adelaide, South Australia, Australia
  2. Paracelsus Medical University, Salzburg, Austria
  3. University of Birmingham, Birmingham, UK
  4. Hospital Angeles Puebla, Puebla City, Mexico
  5. UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
  6. Novo Nordisk, Søborg, Denmark
  7. University of Minnesota Medical School, Minneapolis, MN, USA
  8. University at Buffalo, Buffalo, NY, USA
  9. University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Background: STEP TEENS (NCT04102189) was the first phase 3a trial to examine efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg (sema) + lifestyle intervention in adolescents (12–<18 yrs) with obesity (BMI ≥95th percentile), or overweight (BMI ≥85th percentile) with ≥1 weight-related comorbidity.

Methods: Participants were randomised 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), ≥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.

Results: Of 201 adolescents (62.2% female; mean age 15.4 yrs, body weight 107.5 kg, BMI 37.0 kg/m2) randomised, 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 lipids (except HDL) were reduced with sema (p<0.05). Sema improved overall weight-related QoL (p=0.038) and physical comfort (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 improvements in cardiometabolic risk factors and QoL. Sema was generally well tolerated, with a safety profile consistent with the GLP-1RA class.