Endocrine Abstracts

JOINT3349

Background: Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, has been approved for treating obesity caused by genetic disorders affecting the leptin-melanocortin pathway. This single-center case series evaluates six pediatric patients who began treatment between March and December 2024.

Methods: Baseline assessments included anthropometric measurements, laboratory tests, and adapted questionnaires for ages below and above 12 years. The questionnaires included hunger symptoms and impact of hyperphagia from patient and caregiver perspectives. Two patients with Bardet-Biedl Syndrome (BBS) had completed six months of follow-up at the time of submission, allowing comparisons between baseline and six-month evaluations.

Results: The study included six children (two males, four females) aged 5 to 15 years. At baseline, the median BMI-for-age z-score was +3.25 (range: 2.84–5.8), and the median body fat percentage was 35.43% (range: 24.5–42.5%). Genetic diagnoses included four patients with BBS (one compound heterozygosity for BBS1 and one for BBS2, heterozygosity for BBS4 and BBS19, and homozygosity for BBS9), one patient with a homozygous pro-opiomelanocortin (POMC) deficiency, and another with compound heterozygosity for leptin receptor (LEPR) deficiency. 50% of the patients had prediabetes, and 50% had hypertriglyceridemia at baseline. Hunger scores for patients <12 years ranged from 9–13 out of 15, while older patients scored between 5–10 out of 12. The hyperphagia impact scores ranged from 13–21 out of 24 in younger patients and 10–21 out of 24 in older ones. The highest-rated symptom was “persistent hunger after eating,” and hyperphagia most affected “leisure and free time” and “relationships with family and friends.” Family members reported the greatest impact on “mood and emotions” and “relationships”. After six months, two BBS patients showed improvements in anthropometric and quality-of-life measures. A 6-year-old patient’s hunger score decreased from 9 to 8, hyperphagia impact from 13 to 9, family impact from 11 to 8, and BMI reduced by −2.02 kg/m². A 13-year-old patient’s hunger score dropped from 6 to 4, hyperphagia impact from 10 to 7, family impact from 15 to 14, and BMI decreased by −5.11 kg/m².

Conclusions: Preliminary results suggest setmelanotide improves BMI, hunger scores, and hyperphagia’s impact on patients and families. Further analysis when the follow-up for the other patients has been completed will provide more insight into the consistency and magnitude of these changes. While results are promising, ongoing evaluation may help assess the durability of setmelanotide’s effects and its long-term impact on obesity management and quality of life.