Emerging Data Suggest Survodutide Targets Liver Fat More Rapidly Than Weight Loss: Lee Kaplan, MD, PhD

The understanding of how novel agents like survodutide (Boehringer Ingelheim) may influence body composition and liver health beyond simple weight loss is evolving with emerging data from the phase 3 SYNCHRONIZE-1 (NCT06066515) and SYNCHRONIZE-MASLD (NCT06309992) trials, according to Lee Kaplan, MD, PhD, director of The Obesity and Metabolism Institute, Massachusetts General Hospital in Boston, and chair of the SYNCHRONIZE program executive committee.

Topline results from SYNCHRONIZE-1 presented by Kaplan today at the 86th Scientific Sessions of the American Diabetes Association (ADA) showed that adults with obesity or overweight without type 2 diabetes achieved an average weight loss of up to 16.6% at 76 weeks with survodutide, a dual glucagon/glucagon-like peptide-1 (GLP-1) receptor agonist, compared with 3.2% for placebo. More detailed analyses presented at the meeting suggest that the drug’s metabolic benefits may extend beyond overall weight reduction.

In an interview with The American Journal of Managed Care^®, Kaplan explained that weight loss achieved through behavioral, surgical, or pharmacologic interventions generally includes reductions in both fat mass and lean mass. Because individuals with obesity often have higher baseline lean mass due to the mechanical demands of carrying excess weight, some decline in lean tissue is expected as body weight decreases.

However, body composition analyses from a prespecified MRI substudy of SYNCHRONIZE-1 found that lean mass accounted for no more than 10.8% of total tissue mass change at the highest dose of survodutide, indicating that weight loss was driven predominantly by fat loss. At the same time, participants experienced reductions of up to 34.0% in visceral fat volume after 76 weeks of treatment. Kaplan noted that “decrease in visceral fat, I think, has an even stronger basis for improving metabolic health than the preservation of muscle, which is still an open question.”

The liver fat findings were particularly notable. In the same SYNCHRONIZE-1 substudy, survodutide reduced liver fat by up to 63.1% relative to baseline. According to Kaplan, excess visceral adiposity and hepatic fat are key drivers of metabolic dysfunction and are closely linked to inflammation and impaired liver health. He pointed out that reductions in liver fat appeared early, suggesting a treatment-specific effect: “What we’re seeing is something that is specific to the treatment and is specific to the liver more than [it] is just an association with the amount of weight loss.” He added that “loss of liver fat is associated in numerous studies with improvement in MASH [metabolic dysfunction–associated steatohepatitis], with decreased inflammation, decrease in liver cell injury, and decrease in fibrosis.”

The drug’s dual mechanism may contribute to these effects. While GLP-1 receptor activation helps reduce appetite and increase satiety, glucagon receptor agonism is thought to act directly on the liver to reduce hepatic fat, regulate metabolic function, resolve inflammation, and improve fibrosis.

Additional support for these observations came from the phase 3 SYNCHRONIZE-MASLD trial, which enrolled adults with obesity or overweight who had metabolic dysfunction–associated steatotic liver disease (MASLD) with evidence of inflammation and/or fibrosis. After 48 weeks, up to 84.2% of participants receiving survodutide achieved at least a 30% relative reduction in liver fat compared with 24.3% in the placebo group, while body weight declined by up to 12.2% versus 1.0% with placebo.

Investigators also reported that 61.0% of treated participants achieved liver fat normalization, defined as liver fat content below 5%, compared with 5.7% of those receiving placebo. Positive trends were observed in liver-related biomarkers, including alanine transaminase levels, suggesting reductions in hepatic inflammation.

For clinicians, the findings highlight a broader shift in obesity management from focusing solely on body weight to evaluating outcomes such as body composition, visceral adiposity, liver fat content, and other markers of metabolic health. Together, the SYNCHRONIZE-1 and SYNCHRONIZE-MASLD data suggest that glucagon/GLP-1 dual agonism may offer benefits that extend beyond weight loss alone, particularly for patients at risk of obesity-related liver disease and metabolic dysfunction.

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.