Novel GLP-1/FGF21 dual agonist shows promise in treatment of MASLD with T2DM

The glucagon-like peptide-1 (GLP-1) and fibroblast growth factor 21 (FGF21) dual agonist HEC88473 demonstrates an acceptable safety profile and potential efficacy in the management of patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM).

Researchers performed a randomized, double-blind, placebo-controlled phase Ib/IIa trial to evaluate the safety and efficacy of a novel GLP-1/FGF21 dual agonist HEC88473 for the treatment of MASLD combined with T2DM. Sixty eligible patients were randomly allocated to receive HEC88473 (5.1, 15.3, 30.6, 45.9, or 68.0 mg) or placebo via weekly subcutaneous injection for 5 weeks.

Treatment with HEC88473 resulted in a reduction in MRI-proton density fat fraction (MRI-PDFF) in a dose-proportional manner after 5 weeks.

The largest relative mean change was ‒47.21 percent (p=0.0143) in the 30.6-mg cohort as opposed to ‒15.05 percent in the placebo arm. A higher proportion of >30-percent relative reductions was observed in patients with baseline PDFF >8 percent.

HEC88473 also resulted in substantial decreases in the levels of glycated haemoglobin (HbA1c), as well as fasting and postprandial glucose. The largest mean change in HbA1c reached ‒1.10 percent in the 68.0-mg cohort relative to ‒0.31 percent in the placebo group.

Additionally, lipid profiles improved among participants.

With regard to safety, most adverse events were either mild or moderate in severity, with gastrointestinal disorders (48.3 percent) being the most common.

“A 5-week treatment with HEC88473 was generally safe and well tolerated, with multiple positive effects observed, including reduced liver fat, and improved glycaemic control, insulin resistance, and lipid metabolism, indicating comprehensive improvement in metabolic syndrome,” the researchers said.