Nephron · 2026
Sequential liraglutide and setmelanotide therapy in Bardet-Biedl Syndrome: metabolic and renal outcomes in a real-world case report and literature review.
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Pasquariello Tommaso, Secondulfo Floriana, Roscini Anna Rita, Nardi Elisabetta, Prosperi Enrico, Capasso Giovambattista, Perna Alessandra F, Zacchia Miriam
Аннотация
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.
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.