Clinically Meaningful Outcomes after 1 Year of Treatment with Setmelanotide in an Adult Patient with a Variant in SH2B1.

Introduction: Monogenic obesity is caused by a unique genetic dysfunction, often appears in childhood, and can be accompanied by neuroendocrine, skeletal, developmental, and behavioral disorders, among other manifestations. Some variants in the SH2B1 gene have been suggested as strong candidates for the development of autosomal dominant obesity.

Case presentation: We describe here the clinical response after 1 year of setmelanotide treatment in a 22-year-old patient with an SH2B1 variant. After 3 months of treatment, our patient lost 5.4% of body weight. This period was followed by a 3-month period of noncompliance, in which the patient gained 4% body weight. After reinstating daily drug administration, the patient showed a 19.5% reduction in body weight and a clear improvement in all hunger scales after 1 year of treatment.

Conclusion: These results indicate that the changes seen are drug dependent and provide positive evidence for the administration of setmelanotide in adult patients with heterozygous variants in the SH2B1 gene.