Work

Impact of the Melanocortin-4 Receptor Agonist Setmelanotide on MASLD and Kidney Function in Bardet-Biedl Syndrome

Year: 2025

Type: article

Abstract: BACKGROUND AND OBJECTIVE: The melanocortin-4 receptor agonist setmelanotide compensates for upstream gene defects in the brain leptin-melanocortin pathway and reduces hyperphagia and obesity in selected monogenic obesity forms and Bardet-Biedl syndrome (BBS). We aimed to evaluate the short-term impact of setmelanotide treatment in BBS presenting original real-world data focusing on metabolic dysfunction-associated steatotic liver disease (MASLD) and kidney function. METHODS: This monocentric, prospective observational cohort study was performed between June and December 2023 and included patients above the age of 6 years with genetically confirmed BBS, obesity, and/or hyperphagia and planned setmelanotide therapy. Ultrasound examination of the liver including shear wave elastography, dispersion and attenuation imaging (ATI), a bioimpedance analysis, and a hyperphagia questionnaire survey were applied in addition to clinical data collection. RESULTS: Twenty-six patients with BBS (mean age 19.2 years, range [6.2; 51.8]; mean body mass index (BMI) z-score 2.95, range [1.32; 4.84]) were included. All were classified with MASLD (54% S3, 23% each S1 and S2). After 6 months of setmelanotide treatment, estimated glomerular filtration rate increased up to 10.1 mL/min/1.73 m² (95% confidence interval (CI) [4.3; 15.9]). The following parameters also improved: BMI z-score -0.5 (95% CI [-0.6; -0.3]); hyperphagia score -12.3 (95% CI [-15.5; -9.0]); total body fat -3.1% (95% CI [-5.7; -0.5]); ATI -0.14 dB/cm/MHZ (95% CI [-0.17; -0.11]). A total of 85% of patients exhibited either resolution of MASLD or stabilization at grade S1. MASLD improvement correlated only with liver size, not BMI reduction. CONCLUSION: Setmelanotide treatment is associated with improvement of MASLD independent of BMI reduction as well as increased glomerular filtration rate in BBS.

Source: The Journal of Clinical Endocrinology & Metabolism

DOI: 10.1210/clinem/dgaf483