Tirzepatide shows promise for weight and behavioral management in a 31-year-old female with Smith-Magenis syndrome.

Smith-Magenis syndrome (SMS) is a complex neurodevelopmental disorder caused by a deletion on chromosome 17p11.2, impacting the RAI1 gene. This haploinsufficiency leads to severe maladaptive behaviors like self-injury and aggression, alongside early-onset obesity and profound food-related issues, often resistant to conventional weight management. Tirzepatide, a dual GIP and GLP-1 receptor agonist, has revolutionized obesity treatment by offering synergistic effects on glucose and weight regulation, surpassing single GLP-1R agonists. This case explores its utility in the challenging context of SMS.