Novel glucagon/GLP-1 receptor dual agonist helps reduce liver fat

In patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or steatohepatitis (MASH), treatment with the novel glucagon and GLP-1 receptor dual agonist DD01 is associated with rapid reductions in liver fat, according to a phase II study.

The study included 67 adult patients (mean age 48.4 years, 63 percent female, 85 percent White) with MASLD or MASH who were overweight or had obesity (BMI ≥25 kg/m²). All participants had to have liver fat content of at least 10 percent with metabolic risk factors, or if the biopsy confirmed MASH with a nonalcoholic fatty liver disease activity score of at least 4.

The participants were randomly assigned to receive DD01 40 mg (n=33) or matched placebo (n=34). Treatment was administered as once-weekly subcutaneous injections over 48 weeks, dose-escalated over 2 weeks.

The primary endpoint was a ≥30-percent relative reduction in liver fat, as measured using MRI-proton density fat fraction at week 12. Safety was also assessed.

At week 12, 76 percent of DD01-treated participants vs 12 percent of placebo-treated participants achieved the primary endpoint (adjusted common odds ratio, 28.8, 95 percent confidence interval, 7.2–115.2; p<0.0001).

Treatment-emergent adverse events (AEs) occurred in 85 percent of participants in the DD01 group and 68 percent in the placebo group. The most common AEs were nausea, diarrhoea, and vomiting. Treatment-emergent AEs led to treatment discontinuation in 12 percent and 3 percent of participants in the DD01 and placebo groups, respectively. Treatment-emergent serious AEs, including abdominal pain and acute cholecystitis, occurred in the DD01 group (6 percent). There were no reports of death in either treatment group.