Endocrine Abstracts

JOINT1566

Objective: Setmelanotide, an MC4R agonist, is approved for the treatment of obesity in patients with POMC, LEPR, and PCSK1 deficiencies, as well as in Bardet-Biedl Syndrome (BBS). There is little real-world evidence for the efficacy and safety of setmelanotide. This study aimed to evaluate the clinical characteristics and follow-up outcomes of patients treated with setmelanotide at our center.

Methods: The study included five patients; three patients with POMC deficiency, one with LEP mutation, and one with BBS treated with setmelanotide. The effects of setmelanotide on body weight, associated measures, hunger score, and quality of life were examined.

Results: The mean age of the patients was 17.1±5.04 years (range: 11.5–24 years). Three patients were female and two were male. The duration of treatment ranged from 3 to 14 months. Except for the patient with BBS, all patients achieved a decrease in their BMI by more than 5% during the treatment. Before therapy, the mean BMI was 38.78±5.99 kg/m² (32.36-48.20) and the mean BMI SDS was 3.35±0.96 (2.14-4.59). After therapy, the mean BMI was 35.31±7.43 kg/m² (29.10-47.80), the mean BMI SDS was 2.98±1.15 (ra1.78-4.63), and the mean percentage decrease in BMI was -9.22±8.44% (range: 0.80-21.30). All patients showed a significant decrease in their hunger scores and an improvement in their quality of life (QoL) scores. The baseline hunger score was 8.60±1.34 (range: 7-10) and decreased to 3.60±2.88 (range: 1-8) after treatment. Similarly, the mean baseline QoL was 96.60±26.40 (range: 62-120) and improved to 106.20±22.28 (range: 68-124) after treatment. After five months of treatment, the patient with the LEPR gene variant had a -9.9% decrease in BMI but had to stop treatment for one month due to depression. In the ninth month of the follow-up period, BMI decreased by -0.8%, and treatment was discontinued due to worsening depression symptoms. Additionally, adverse events such as nausea in four patients, hyperpigmentation in four patients, headache in two patients, and pain at the injection site in two individuals were observed. However, these adverse events did not necessitate discontinuation of treatment.

Conclusion: Setmelanotide provides significant weight control in POMC and LEPR deficiencies but has a more limited effect in BBS. It can also provide significant reduction in hunger scores and improvement in QOL scores in all patients, including BBS. Long-term, real-life data with more patients are needed regarding setmelanotide treatment.

Key Words: Setmelanotide, Genetic, Obesity, POMC, LEPR, BBS