Tirzepatide for weight and behavior management in a patient with Smith-Magenis syndrome.

This case report describes the use of tirzepatide — a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist — in a 31-year-old woman diagnosed with Smith-Magenis syndrome (SMS), a rare neurodevelopmental disorder associated with intellectual disability, behavioral dysregulation, and hyperphagia-driven obesity. The patient had a lifelong history of obesity and aggressive behaviors that had not responded adequately to standard management. Following initiation and titration of tirzepatide, the authors report that the patient achieved approximately 9.4% body weight loss (~7.3 kg) over 10 months, along with improvements in fasting glucose levels. Caregivers also noted behavioral benefits, including reduced food-seeking behavior and impulsivity, and quantitative analysis reportedly showed a significant reduction in aggression. The treatment was described as well tolerated. The authors hypothesize that tirzepatide may engage both metabolic and central nervous system pathways relevant to the SMS phenotype. Key limitations include the single-patient design, the absence of a control condition, and the inherent difficulty in attributing behavioral improvements to tirzepatide alone in a complex neurodevelopmental disorder.

Why this grade: This is a single-patient case report with no control group, making it insufficient to establish efficacy or generalizability despite involving a human subject.