Effectiveness of the Dual GLP-1R/GCGR Agonist Mazdutide in GSD IXc: A Case Report.
Mazdutide showed a significant reduction in body weight and improvements in liver stiffness in a patient with GSD IXc, but further studies are needed to validate these findings.
Where it sits
this study against the rest of the mazdutide (ibi362) corpusSummary and findings
This case report evaluated the effects of mazdutide on weight management, hepatic function, and glycemic control in a 24-year-old woman with glycogen storage disease type IXc (GSD IXc). After 4 months of treatment, the patient experienced a 20.6% reduction in body weight and significant improvements in liver stiffness and controlled attenuation parameter. No therapeutic claims are made regarding the efficacy of mazdutide.
Abstract
<b>Background</b>: Glycogen storage disease type IXc (GSD IXc), caused by pathogenic PHKG2 variants leading to phosphorylase kinase deficiency, is associated with the most unfavorable prognosis among GSD IX subtypes. Patients are at markedly increased risk of progressive hepatic fibrosis and cirrhosis, for which no established disease-modifying therapies exist. Mazdutide, a dual glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR) agonist approved for type 2 diabetes and obesity, has demonstrated beneficial effects on hepatic metabolism, steatosis, and fibrosis in preclinical studies. <b>Objectives</b>: To explore the efficacy of mazdutide for weight management, hepatic function, and glycemic control in an overweight patient with GSD IXc. <b>Methods</b>: We describe a 24-year-old woman with a 20-year history of GSD who presented with chronically elevated liver enzymes, dyslipidemia, and progressive weight gain (BMI 27.4 kg/m<sup>2</sup>). Genetic testing identified a homozygous PHKG2 c.765del variant, confirming the diagnosis of GSD IXc. Clinical data were collected throughout the mazdutide treatment course and follow-up, including body weight, liver stiffness, serum transaminases, lipid profiles, and glycemic parameters. Written informed consent was obtained. <b>Results</b>: After 4 months of treatment, the patient achieved a 20.6% reduction in body weight (from 85.0 to 67.5 kg). Compared with the most recent assessment performed 4 years prior, liver stiffness measurement (LSM) by transient elastography was 55% lower (29.3 to 13.1 kPa), and controlled attenuation parameter (CAP) was 18% lower (309 to 254 dB/m). Improvements in liver enzymes and partial lipid profiles were observed. Notably, the patient discontinued uncooked cornstarch (UCCS) for one month during maintenance therapy and short-term continuous glucose monitoring showed no level 2 hypoglycemia. <b>Conclusions</b>: Mazdutide may represent a promising therapeutic strategy for patients with GSD IXc accompanied by metabolic abnormalities, obesity, and hepatic fibrosis. Validation through larger cohorts and mechanistic studies is warranted.
Background
This paper addresses the efficacy of mazdutide in managing glycogen storage disease type IXc (GSD IXc), a condition associated with severe metabolic complications and no established therapies. Prior studies have indicated that mazdutide may improve hepatic metabolism and fibrosis in preclinical models. This case report is significant as it explores the potential of mazdutide in a human patient with GSD IXc.
Methods
The study describes a 24-year-old woman with a 20-year history of GSD IXc, confirmed by genetic testing for a homozygous PHKG2 c.765del variant. Clinical data were collected during the 4-month mazdutide treatment, focusing on body weight, liver stiffness, serum transaminases, lipid profiles, and glycemic parameters. The specific dose of mazdutide and the treatment route are not reported in the abstract.
Results
After 4 months of treatment, the patient achieved a 20.6% reduction in body weight, with liver stiffness measurement decreasing by 55% and controlled attenuation parameter lowering by 18%. Improvements in liver enzymes and lipid profiles were also observed, although specific numeric values for these changes are not reported in the abstract.
Interpretation
The findings suggest that mazdutide may have a positive impact on weight and liver function in this patient with GSD IXc. However, the clinical significance of the observed changes, particularly in liver stiffness and lipid profiles, remains unclear without a control group for comparison. The limitations of a single-case report and lack of broader validation restrict the conclusions that can be drawn about the efficacy of mazdutide in a larger population.
Key findings
- 20.6% reduction in body weight from 85.0 to 67.5 kg after 4 months.
- Liver stiffness measurement decreased by 55% from 29.3 to 13.1 kPa.
- Controlled attenuation parameter was 18% lower from 309 to 254 dB/m.
- No level 2 hypoglycemia observed during short-term continuous glucose monitoring.
Limitations
- Single case report with no control group.
- No specific dose or treatment route reported.
- Short follow-up period of 4 months.
- Lack of larger cohort validation.