Boehringer Ingelheim’s Phase 3 SYNCHRONIZE-1 and SYNCHRONIZE-MASLD trials show survodutide significantly reduces body weight, visceral fat, and liver fat while preserving lean mass, reinforcing its potential as a dual glucagon/GLP-1 therapy for obesity and MASLD.
Written By: Dr. Preethi Putti, PharmD
Reviewed By: Pharmacally Editorial Team
Boehringer Ingelheim has reported new Phase 3 results from the SYNCHRONIZE-1 and SYNCHRONIZE-MASLD trials, showing significant reductions in body weight, visceral fat, and liver fat across adults living with obesity or overweight and patients with MASLD. The findings further support the potential of survodutide (BI 456906), an investigational glucagon/GLP-1 receptor dual agonist, to address key drivers of metabolic dysfunction associated with obesity.
Results were presented at the American Diabetes Association (ADA) 2026 Scientific Sessions and published simultaneously in The New England Journal of Medicine and Nature Medicine.
Dual Mechanism of Action
Survodutide combines glucagon receptor agonism with GLP-1 receptor activation. GLP-1 activity reduces appetite and increases satiety, while glucagon receptor activation is thought to help reduce liver fat and improve metabolic function. The dual mechanism may offer benefits across obesity and obesity-related metabolic disorders, including MASLD.
SYNCHRONIZE-1: Obesity and Overweight
The 76-week Phase 3 SYNCHRONIZE-1 trial (NCT06066515) enrolled 725 adults with obesity or overweight who did not have type 2 diabetes. Using the efficacy estimand, survodutide achieved up to 16.6% mean weight loss compared with 3.2% for placebo (p<0.0001). MRI substudy analyses provided additional insight into body composition changes: participants achieved reductions of up to 34.0% in visceral fat and 63.1% in liver fat relative to baseline. Lean mass accounted for no more than 10.8% of total tissue mass change at the highest dose, indicating that weight loss was driven primarily by reductions in fat mass.
SYNCHRONIZE-MASLD: Liver Fat Reduction
The 48-week SYNCHRONIZE-MASLD trial (NCT06309992) enrolled 218 adults with obesity or overweight and MASLD with evidence of inflammation and/or fibrosis, including patients with and without type 2 diabetes. Survodutide met both co-primary endpoints. Up to 84.2% of participants achieved at least a 30% relative reduction in liver fat content compared with 24.3% in the placebo group (p<0.0001). Body weight reductions reached up to 12.2% versus 1.0% with placebo. 61.0% of treated patients reached liver fat normalization (<5%) compared with 5.7% of placebo-treated participants. Investigators also observed favorable trends across liver-related biomarkers, including alanine aminotransferase (ALT), supporting potential reductions in hepatic inflammation.
Safety Profile
The safety profile remained consistent with the incretin drug class. The most common adverse events were gastrointestinal, including nausea, vomiting, diarrhea, and constipation, occurring primarily during dose escalation. In SYNCHRONIZE-1, treatment discontinuation due to gastrointestinal adverse events occurred in 19.0% of survodutide-treated patients versus 2.9% of placebo recipients. While this discontinuation rate is somewhat higher than reported in other GLP-1 agonist trials, no new safety signals emerged in either study.
Expanding Development Program
The clinical program continues to expand. Ongoing Phase 3 studies include SYNCHRONIZE-2 in adults with obesity and type 2 diabetes and SYNCHRONIZE-CVOT in patients with cardiovascular disease, chronic kidney disease, or cardiovascular risk factors. Additional studies include SYNCHRONIZE-JP in Japan and SYNCHRONIZE-CN in China.
Meanwhile, the Phase 3 LIVERAGE and LIVERAGE-Cirrhosis trials are evaluating survodutide in adults with metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis, including compensated cirrhosis. Survodutide has also received FDA Fast Track designation and Breakthrough Therapy designation for MASH.
Global Impact
With more than one billion people worldwide living with obesity and up to 75% developing MASLD, the latest findings reinforce the potential of dual glucagon/GLP-1 receptor agonism to address both excess weight and the underlying metabolic dysfunction that drives obesity-related disease. Together, these results strengthen survodutide’s positioning as a therapy capable of redefining obesity and MASLD treatment by targeting fat reduction, liver health, and metabolic improvement.
References
survodutide-phase-3-fat-loss-obesity-dual-agonist-data | Boehringer Ingelheim
About the Writer
Dr.Preethi Putti, PharmD (LinkedIn) is a pharmaceutical researcher with experience in healthcare and pharmaceutical market research and competitive intelligence. She specializes in analyzing drug pipelines, clinical data, and industry trends and translating complex scientific data into clear and structured medical content. Strong foundation in clinical research, data interpretation, and evidence-based healthcare analysis. Committed to advancing a global career in clinical research and healthcare innovation.