Survodutide Reduces Weight and Liver Fat in Obesity and MASLD

Survodutide, a once-weekly injectable dual glucagon/GLP-1 receptor agonist, achieved substantial weight loss and liver fat reduction in two phase 3 trials. Data presented at the American Diabetes Association Scientific Sessions in New Orleans showed weight loss of approximately 15% in patients with obesity and significant improvements in liver health for those with metabolic dysfunction-associated steatotic liver disease (MASLD).

How did survodutide perform in clinical trials?

In the SYNCHRONIZE-1 trial, which included 725 adults with overweight or obesity but no type 2 diabetes, researchers found significant weight reductions. According to Carel le Roux, MD, PhD, participants using a 6 mg dose saw a mean weight change of 16.6%, while those on 3.6 mg saw a 15.3% reduction over 76 weeks.

The results were stark compared to the placebo group, which saw a 3.2% change. Roughly 85% of participants on the 6 mg dose achieved a weight reduction of 5% or more, compared to 38.8% in the placebo group.

A separate trial, SYNCHRONIZE-MASLD, focused on 216 adults with obesity and risk for MASLD, including some with type 2 diabetes. Lee M. Kaplan, MD, PhD, reported that 84.2% of the survodutide group achieved a 30% or greater reduction in liver fat content, while only 24.3% of the placebo group did.

Did You Know? Participants in the SYNCHRONIZE-1 trial experienced a waist circumference reduction of about 14 cm, which Dr. Carel le Roux noted is equivalent to at least six notches on a belt.

Why is this drug’s impact on liver health significant?

The drug’s ability to target more than just weight is a key differentiator. In the SYNCHRONIZE-1 MRI substudy, the highest dose of survodutide led to a 63.1% reduction in liver fat content and a 34% reduction in visceral adipose tissue.

For those with liver-specific complications, the SYNCHRONIZE-MASLD trial showed that survodutide normalized liver fat content in 60% of participants. Dr. Kaplan stated the drug significantly reduced liver fat, injury, inflammation, and fibrosis.

Beyond the liver, the drug improved several cardiometabolic risk factors. Researchers reported reductions in blood pressure, fasting plasma glucose, and lipids, including LDL cholesterol and triglycerides, while HDL cholesterol increased.

Expert Insight: Samantha Carter notes that the shift toward dual agonism represents a transition from viewing weight loss as the primary goal to focusing on multiorgan health. By addressing both GLP-1 and glucagon receptors, the therapy could allow for a more precision-based approach to obesity care, where treatment is guided by a patient’s specific metabolic risks.

What are the side effects and safety concerns?

The safety profile of survodutide mirrors other drugs in the GLP-1 receptor agonist class. The most common adverse events were mild or moderate gastrointestinal symptoms.

Professor Carel le Roux

In the SYNCHRONIZE-1 trial, GI symptoms occurred in 80.9% to 89.7% of the survodutide groups, compared to 47.9% for the placebo. About 23% to 24.8% of participants in the treatment arms withdrew due to adverse events, while only 5.4% of the placebo group did.

Similarly, in the SYNCHRONIZE-MASLD trial, 19.9% of participants discontinued the study due to GI-related adverse events, compared to 4.3% in the placebo group.

What may happen next for survodutide?

The focus of future research may shift toward long-term cardiovascular and liver outcomes. Jaime Almandoz, MD, MBA, suggested that the next steps could involve determining the specific cardiovascular outcomes and the impact on liver fibrosis beyond noninvasive tests.

Researchers may also seek to identify which specific patient populations benefit most from this dual-agonist approach. This could lead to a scenario where liver health becomes a primary factor in choosing between different obesity therapeutics.

Frequently Asked Questions

What is survodutide?
It is a once-weekly injectable dual glucagon/GLP-1 receptor agonist developed by Boehringer Ingelheim and Zealand Pharma for treating overweight, obesity, and liver-related metabolic dysfunction.

How does it affect blood sugar in non-diabetics?
In the SYNCHRONIZE-1 trial, survodutide decreased mean HbA1c levels by up to 0.27 percentage points. Additionally, 30 to 32 participants regressed from prediabetes to normoglycemia.

Did the trials show any impact on liver fibrosis?
Yes, the SYNCHRONIZE-MASLD trial reported improvements in liver fibrosis based on noninvasive tests, including FibroScan.

How do you think a focus on multiorgan health might change the way we approach weight management?