Introduction & Objective: To explore the effect of mazdutide, a once-weekly GLP-1 and glucagon receptor dual agonist, on liver steatosis.
Methods: In the GLORY-1 phase 3 trial (NCT05607680), 610 Chinese adults with a BMI of 28 kg/m2 or more, or 24 kg/m2 or more and at least one weight-related comorbidity were randomly assigned 1:1:1 to receive once-weekly, subcutaneous mazdutide 4 mg, mazdutide 6 mg or placebo for 48 weeks. A subpopulation of participants had MRI scan and liver fat content (LFC) measurement by MRI-proton density fat fraction (MRI-PDFF). Change from baseline at week 48 in LFC was an exploratory endpoint of the study.
Results: In participants with baseline LFC of 5% or more and 10% or more, treatment with mazdutide 4 mg or 6 mg for 48 weeks led to marked and dose-dependent reductions in LFC. Of note, a mean relative reduction of 80.2% was achieved with mazdutide 6 mg among participant with baseline LFC of 10% or more. In participants with baseline LFC of 5% or more, compared with placebo, substantially more participants with mazdutide 4 mg and 6 mg achieved ≥30% relative reduction in LFC, ≥50% relative reduction in LFC and normalization of LFC (<5%) at week 48 (Figure).
Conclusion: In Chinese adults with overweight or obesity and liver steatosis, mazdutide 4 mg and 6 mg provides robust reductions in LFC.
L. Ji: None. H. Jiang: None. Y. Zhang: None. L. Lv: None. J. Gu: None. Z. Liu: Employee; Innovent Biologics. Y. Wang: Employee; Innoventbio. H. Deng: Employee; Innovent. L. Qian: Employee; Innoventbio.
