Sequential liraglutide and setmelanotide therapy in Bardet-Biedl Syndrome: metabolic and renal outcomes in a real-world case report and literature review

Introduction: Bardet–Biedl syndrome (BBS) is a syndromic ciliopathy characterized by multiple clinical features, including obesity and kidney disease. Therapeutic options remain limited. Setmelanotide, a melanocortin-4 receptor (MC4R) agonist, is approved for obesity in BBS, but real-world data in adults is scarce. This case highlights the synergistic metabolic and nephroprotective effects of a sequential therapeutic strategy combining a glucagon-like peptide-1 (GLP-1) receptor agonist and a MC4R agonist. Case Presentation: We report the case of a 37-year-old male with genetically confirmed BBS due to compound heterozygous likely pathogenic BBS10 variants presenting with obesity, insulin resistance, dyslipidemia, albuminuria and metabolic dysfunction–associated steatotic liver disease (MASLD). Treatment with liraglutide induced modest weight loss (–3.4%, BMI 35.2→34 kg/m²), improved urinary albumin-to-creatinine ratio (uACR) and liver enzymes levels within 8 months. Following discontinuation of liraglutide, setmelanotide therapy was subsequently initiated. After 12 months of treatment, the patient achieved a 10.5% weight loss compared with baseline (BMI 35.2→31.5 kg/m²), normalization of liver transaminases, reduced liver stiffness, and sustained improvement in uACR, while eGFR remained stable. Fasting insulin and HOMA-IR improved. Metformin, statin, and fenofibrate were discontinued, though fenofibrate was later reintroduced for hypertriglyceridemia. Two interventional studies (n≃10–40, 3–52 weeks) similarly reported consistent reduction in metabolic syndrome burden (METs-Z-BMI-score), liver steatosis, stiffness, and enzymes, while renal biomarkers showed stabilization or improvement, supporting potential hepatoprotective and reno-protective effects. Conclusion: Setmelanotide promoted clinically meaningful weight loss and improved liver, kidney, and metabolic parameters in an adult patient carrying BBS10-likely pathogenic variants. Together with emerging evidence for interventional studies, these findings suggest that MC4R agonism may confer organ-level and cardiometabolic benefits beyond weight reduction.