Mazdutide, a Dual GLP-1R/GCGR Agonist, Shows Effectiveness in Glycogen Storage Disease IXc

Glycogen storage disease type IX (GSD IX) is a rare inherited metabolic disorder caused by phosphorylase kinase (PhK) deficiency, impairing glycogen breakdown. GSD IXc, specifically due to mutations in PHKG2, carries the most severe prognosis, leading to progressive hepatic fibrosis, cirrhosis, and end-stage liver disease. Current standard-of-care lacks established therapies for this secondary liver disease, leaving a critical unmet need. Pathological glycogen accumulation in hepatocytes triggers de novo lipogenesis, exacerbating liver injury.

This case report details the treatment of a patient with Glycogen Storage Disease type IXc (GSD IXc). The patient, previously on semaglutide 1.0 mg weekly, was switched directly to Mazdutide 4 mg via subcutaneous injection once weekly for a 16-week initial treatment phase, with no washout period. The study aimed to evaluate the effectiveness of Mazdutide in improving the clinical phenotype and mitigating liver disease progression, including markers of hepatic fibrosis and glycogen accumulation, in this high-risk patient.

Mazdutide administration for 16 weeks demonstrated effectiveness in managing the clinical manifestations of Glycogen Storage Disease type IXc (GSD IXc) in the reported patient. The dual GLP-1R/GCGR agonism of Mazdutide appeared to address key pathophysiological aspects of the disease, including impaired glycogenolysis and pathological glycogen storage. The patient, who transitioned from semaglutide 1.0 mg weekly to Mazdutide 4 mg weekly, showed improvements consistent with the therapeutic goals of mitigating liver disease progression. While specific quantitative results were not provided in the abstract, the observed clinical effectiveness suggests a positive impact on the patient's condition. This represents a novel therapeutic approach for a condition with no established treatments for secondary liver disease. > The dual GLP-1R/GCGR agonist Mazdutide demonstrated clinical effectiveness in a patient with GSD IXc, showing potential to mitigate progressive hepatic fibrosis.