Efruxifermin shows therapeutic potential alongside GLP-1RA medications

Treatment with the Fc–FGF21 analogue efruxifermin is well tolerated and appears to further improve liver health in patients with type 2 diabetes (T2D) and metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis who are already on a GLP-1RA, according to a phase IIb trial.

The trial included 31 adult patients with T2D and MASH fibrosis (F1–F3) on a stable GLP-1RA therapy, including semaglutide (48.4 percent), dulaglutide (45.2 percent), and liraglutide (6.5 percent). These patients were randomly assigned to receive either efruxifermin 50 mg (n=21) or placebo (n=10), administered once weekly for 12 weeks.  

Safety and tolerability of efruxifermin added to a stable dose of GLP-1RA was assessed as the primary endpoint. Secondary endpoints were changes in hepatic fat fraction (HFF), markers of liver injury and fibrosis, and metabolic parameters.

Efruxifermin, when used in addition to a GLP-1RA, was safe and well tolerated. The most common adverse events were mild-to-moderate gastrointestinal events. One patient in the efruxifermin group discontinued treatment due to nausea, whereas another withdrew consent. None of the patients had serious adverse events related to treatment.

In terms of efficacy, efruxifermin produced significant reductions in HFF compared with placebo (–65 percent vs –10 percent; p<0.0001). Efruxifermin also led to improvements in the noninvasive markers of liver injury, fibrosis, glucose, and lipid metabolism while maintaining GLP-1RA–mediated weight loss.