Survodutide Normalizes Liver Fat in 61% of Patients With MASLD in Phase 3 Trial: Lee Kaplan, MD, PhD

At the American Diabetes Association 2026 Scientific Sessions, Boehringer Ingelheim presented phase 3 data showing that survodutide, its investigational glucagon/glucagon-like peptide-1 (GLP-1) dual agonist, normalized liver fat in 6 out of 10 patients with metabolic dysfunction-associated steatotic liver disease (MASLD), a result that experts say signals the drug's potential to address the full spectrum of metabolic disease, not just obesity.

The SYNCHRONIZE-MASLD trial (NCT06309992), a 48-week placebo-controlled study in adults with obesity or overweight and MASLD, met both coprimary end points. Up to 84.2% of survodutide-treated participants achieved at least a 30% relative liver fat reduction vs 24.3% on placebo (P < .0001), and body weight declined by up to 12.2% vs 1.0% with placebo. Critically, 61% of patients using survodutide reached liver fat normalization, defined as liver fat content below 5%, compared with just 5.7% on placebo.

The clinical weight of those reductions was put in context by Lee Kaplan, MD, PhD, director of The Obesity and Metabolism Institute, Massachusetts General Hospital, and chair of the SYNCHRONIZE program executive committee, in an interview with The American Journal of Managed Care®. "A 30% decrease in liver fat is associated with improvement in MASH. A 50% decrease in liver fat has been associated with improvement in fibrosis," the expert explained, adding that the reductions seen with survodutide exceed that threshold and are therefore "associated with improvement in all aspects of MASH [metabolic dysfunction-associated steatohepatitis] and its fibrotic complications."

In the SYNCHRONIZE-1 (NCT06066515) obesity trial, survodutide produced up to 63.1% liver fat reduction and 34% visceral fat reduction, with lean mass representing no more than 10.8% of total tissue change. Kaplan highlighted that the drug's dual mechanism appears to drive "a lesser effect on losing muscle and a greater effect on decreasing visceral fat, one of the most dangerous areas of excess fat."

Concerns about glucagon agonism worsening glycemia were also addressed. "This combination of GLP-1 and glucagon agonism in the right balance actually not only fails to make things worse, but actually improves lipid disorders and glucose disorders," the expert said. Results from SYNCHRONIZE-2 (NCT06066528), enrolling patients with type 2 diabetes, are expected later this year.

Reference

Boehringer Ingelheim’s survodutide phase III trial showed targeted 34% visceral and 63% liver fat reduction, while minimizing lean mass loss in pre-specified analysis, supporting improved metabolic health in people living with obesity. News release. Boehringer Ingelheim. June 7, 2026. Accessed June 7, 2026.