Effectiveness of the Dual GLP-1R/GCGR Agonist Mazdutide in GSD IXc: A Case Report
- 1Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
- 2Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250100, China
Abstract
Background: 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. Objectives: To explore the efficacy of mazdutide for weight management, hepatic function, and glycemic control in an overweight patient with GSD IXc. Methods: 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/m2). 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. Results: 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. Conclusions: 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.
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BibTeX
@article{chen2026effectiveness,
title = {{Effectiveness of the Dual GLP-1R/GCGR Agonist Mazdutide in GSD IXc: A Case Report}},
author = {Yingying Chen and Xueyu Zhong and Xin Guo and Yanli Xia and Cuixia Tian and Juan Zheng},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15208128},
url = {https://www.mdpi.com/2077-0383/15/20/8128},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Effectiveness of the Dual GLP-1R/GCGR Agonist Mazdutide in GSD IXc: A Case Report
AU - Yingying Chen
AU - Xueyu Zhong
AU - Xin Guo
AU - Yanli Xia
AU - Cuixia Tian
AU - Juan Zheng
PY - 2026
DA - 2026/10/01
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15208128
UR - https://www.mdpi.com/2077-0383/15/20/8128
AB - Background: 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. Objectives: To explore the efficacy of mazdutide for weight management, hepatic function, and glycemic control in an overweight patient with GSD IXc. Methods: 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/m2). 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. Results: 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. Conclusions: 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.
SN - 2077-0383
ER -