Diabetology & Metabolic Syndrome (Dec 2024)

Supaglutide alleviates hepatic steatosis in monkeys with spontaneous MASH

  • Qinghua Wang,
  • Yue Zhou,
  • Yunzhi Ni,
  • Zhihong Wang,
  • Yan-Ru Lou,
  • Zunyuan Yang,
  • Li Gong,
  • Yinan Liang,
  • Wen Zeng,
  • Gerald J. Prud’homme

DOI
https://doi.org/10.1186/s13098-024-01513-7
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 16

Abstract

Read online

Abstract Background Glucagon-like peptide 1 (GLP-1) is an incretin hormone and plays an important role in regulating glucose homeostasis. GLP-1 has a short half-life due to degrading enzyme dipeptidyl peptidase-IV and rapid kidney clearance, which limits its clinical application as a therapeutic agent. We demonstrated previously that supaglutide, a novel long-acting GLP-1 analog, exerted hypoglycemic, hypolipidemic, and weight loss effects in type 2 diabetic db/db mice, DIO mice, and diabetic monkeys. In the present study, we investigated supaglutide’s therapeutic efficacy in rhesus monkeys with spontaneous metabolic dysfunction-associated steatohepatitis (MASH). Methods 15 rhesus monkeys with biopsy-confirmed MASH were divided into three groups, receiving supaglutide 50 µg/kg, supaglutide 150 µg/kg, and placebo, respectively, by weekly subcutaneous injection for 3 months. Liver fat content quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF), liver pathology, and metabolic parameters were assessed. Results We found that once-weekly subcutaneous injections of supaglutide for 3 months significantly reduced hepatic fat accumulation, with a 40% percentage decrease in MRI-PDFF from baseline (P < 0.001 vs. Placebo). Treatment with supaglutide alleviated hepatic histological steatosis (nonalcoholic fatty liver disease activity score P < 0.001 vs. Placebo) without worsening of fibrosis, as assessed by ultrasound-guided liver biopsy. Supaglutide concomitantly ameliorated liver injury exemplified by a lowering tendency of hepatic alanine aminotransferase levels. Supaglutide also decreased body weight in a dose-dependent fashion accompanied by decreased food intake, improved lipid profile and glycemic control. Conclusions Supaglutide exerts beneficial effects on hepatic and metabolic outcomes in spontaneous MASH monkeys.

Keywords