Background: Research has been done on genetic causes of obesity, and work has continued on therapies that may help treat some of these genetic mutations. One specific treatment, setmelanotide, known by the trade name Imcivree, approved for use in 2022 for Bardet-Biedl Syndrome (BBS) has shown marked improvement in weight and quality of life in patients with hypothalamic dysfunction as seen in patients with BBS. With the marked improvement in quality of life and weight reduction in BBS patients. This study evaluated the rate of patients who tolerate therapy with setmelanotide as compared to those who discontinued therapy. Methods: A chart review was conducted to evaluate the number of patients started on setmelanotide and the number of patients who discontinued treatment, along with the reasons for discontinuation of treatment. All patients in this study were identified as patients with Bardet-Biedl Syndrome diagnosed by clinical presentation with supportive genetic testing results. Results: Out of 75 patients who were started on setmelanotide, 12 discontinued treatment for various reasons, representing 16% of the study population, similar to Saxenda discontinuation rate of 15.2%. All 12 patients in this study had various degrees of side effects that caused them to discontinue use of the medication, with the most common being hyperpigmentation and severe nausea and vomiting. Other causes for discontinuation were mood disturbance, body aches, anaphylacticlike reaction, need for daily injection, and injection site reaction. Conclusions: Setmelanotide's real world tolerability for patients with genetic causes of obesity matches existing treatment options and warrants further monitoring regarding patient tolerance of the side effects of treatment.