Semaglutide in Youth With Autism Spectrum Disorder

Semaglutide for Metabolic and Adiposity-Related Targets in Youth With Autism Spectrum Disorder (SMART-ASD)

This study is a 6-month, two-arm, RCT which will evaluate the effectiveness and safety of semaglutide in adolescents aged 12-18 years with autism spectrum disorder (ASD) and obesity. The primary outcome is change in body mass index (BMI, kg/m²) from baseline to Month 6. Secondary, descriptive outcomes are changes in metabolic parameters (e.g., lipid levels), side effects, and compliance with semaglutide.

Inclusion Criteria (Semaglutide Group):

• 12-18 years of age
• Epic-confirmed diagnosis of ASD
• Obesity defined as BMI ≥95th percentile for age and sex
• Have Medicaid or other insurance that will cover semaglutide or the parent is willing to pay for semaglutide out of pocket
• Have a parent who is willing to provide informed consent
• Can attend in-person, e-visits, or telehealth visits for 12 months
• English speaking

Exclusion Criteria (Semaglutide Group):

• Healthworks patient who has lost >5% body weight over the past 3 months
• Are on a weight loss-promoting medication such as Metformin or Topamax with a dose change in the past 3 months
• Have Type 1 or Type 2 diabetes
• Have a personal or first-degree family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia 2
• Have been on GLP-1 RAs in the past 12 months
• Have significant GI conditions (e.g., pancreatitis),
• Are pregnant or breastfeeding
• Have catatonia or a condition that may affect compliance and safety

Inclusion Criteria (Historical Control Group):

• Healthworks patients treated between January 1, 2021-December 31, 2025
• 12-18 years of age
• Confirmed diagnosis of ASD
• Have obesity defined as BMI ≥95th percentile for age and sex
• Have BMI and SMM outcomes assessed at M0, M6, or M12
• Age groups 12-14 years old and 15-18 years old and sex matched to youth in the semaglutide group