In large trials, MASLD drug survodutide safely shrank liver fat, body weight
Injectable therapy may lower liver disease risk in people with obesity
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Survodutide, Boehringer Ingelheim’s investigational injectable therapy, significantly reduces liver fat and leads to clinically meaningful weight loss in obese or overweight people with metabolic dysfunction-associated steatotic liver disease (MASLD), a form of steatotic liver disease (SLD).
That’s according to new findings from the now-completed Phase 3 SYNCHRONIZE-MASLD clinical trial (NCT06309992), which tested the treatment candidate in more than 200 obese or overweight adults with MASLD and signs of liver inflammation and/or scarring. Some participants had type 2 diabetes, while others did not.
These results were presented at the American Diabetes Association’s 2026 Scientific Sessions, held earlier this month in New Orleans. The data were also detailed in a study titled “Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a randomized, double-blind, placebo-controlled phase 3 trial,” published in Nature Medicine
In a separate Phase 3 trial, dubbed SYNCHRONIZE-1 (NCT06066515), survodutide also led to significant weight loss in obese or overweight adults without MASLD, while also substantially reducing visceral fat — fat surrounding internal organs — and liver fat. These are key drivers of MASLD and other metabolic diseases.
According to the researchers, these findings suggest the therapy may lower the risk of MASLD in people with obesity.
“I am delighted to see that these data reveal that … survodutide offers a promising approach for people with obesity, and for those with obesity-associated metabolic liver diseases including MASLD,” Lee Kaplan, MD, PhD, chair of the SYNCHRONIZE program executive committee and the director of the Obesity and Metabolism Institute in Boston, said in a press release from Boehringer, which is leading the therapy’s clinical development after coinventing it with Zealand Pharma.
MASLD is characterized by the abnormal accumulation of fat in the liver and typically occurs in the context of other metabolic disorders, such as obesity, diabetes, or elevated blood fat levels.
Up to 75% of obese people may develop MASLD
According to Boehringer, as many as 75% of people living with obesity will develop MASLD, and in about one-third of those cases, the disease may progress to metabolic dysfunction-associated steatohepatitis (MASH), a more severe form marked by liver inflammation and scarring, known as fibrosis. MASH may eventually lead to cirrhosis, or irreversible liver scarring, liver failure, and the need for a liver transplant.
Survodutide, given via under-the-skin (subcutaneous) injections, is designed to simultaneously activate GLP-1 receptor proteins, which help regulate appetite, and glucagon receptor proteins, which are thought to increase energy use.
Activating GLP-1 receptors is intended to reduce hunger and increase feelings of fullness, while activating glucagon receptors may increase fat burning, reduce liver fat, and directly improve liver health by easing inflammation and fibrosis.
In the U.S., survodutide has received fast track and breakthrough therapy designations for treating people with non-cirrhotic MASH and moderate to advanced liver fibrosis. The therapy was also granted Priority Medicines (PRIME) status in the European Union and breakthrough therapy status in China for adults with MASH and fibrosis. These designations are meant to accelerate survodutide’s clinical development and regulatory review.
Previous one-year data from a Phase 2 trial (NCT04771273) involving 295 adults with MASH and biopsy-confirmed liver fibrosis showed that 83% of survodutide-treated participants experienced a significant reduction in MASH severity, compared with 18% of those given a placebo.
Survodutide cut liver fat for over 80% of participants
In SYNCHRONIZE-MASLD, a total of 218 participants were randomly assigned to receive once-weekly subcutaneous injections of either survodutide (6 mg) or a placebo for 48 weeks, or nearly one year. Overall, 216 received at least one dose, and 172 — 80% of the participants — completed the trial.
The study met both of its primary goals, according to the researchers.
Specifically, at about the one-year mark, a significantly greater proportion of participants receiving survodutide achieved at least a 30% reduction in liver fat than those on the placebo (84% vs. 24%). Survodutide-treated participants also lost an average of 12% of their body weight, while those on the placebo lost 1% — a statistically significant difference.
In addition, 61% of participants treated with survodutide reached liver fat normalization, or liver fat content below 5%, compared with 6% of those in the placebo group.
[These new] data … reinforce the potential of survodutide as a truly differentiated … therapy for people living with overweight or obesity and associated metabolic dysfunction.
The therapy also significantly reduced liver volume, liver stiffness (used as a proxy of liver fibrosis,) and blood levels of markers of liver inflammation and damage. Survodutide-treated participants also showed significant reductions in waist circumference, blood pressure, blood sugar levels, and unhealthy blood fats, the data showed.
As expected with therapies targeting GLP-1, gastrointestinal problems were the most commonly reported adverse events and included nausea, vomiting, diarrhea, and constipation. Most were mild to moderate in severity, while serious adverse events were more common in the placebo group than in the survodutide group.
In SYNCHRONIZE-1, which enrolled 725 adults with overweight or obesity, survodutide reduced visceral fat by up to 34% and liver fat by up to 63%, while producing weight loss of up to 17%.
“We are very encouraged by the first results reported from the SYNCHRONIZE program,” David Kendall, MD, chief medical officer of Zealand Pharma, said in a separate company press release. “Data … demonstrated that this novel mechanism achieves targeted visceral and liver fat reduction and reinforce the potential of survodutide as a truly differentiated … therapy for people living with overweight or obesity and associated metabolic dysfunction.”
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