- In the phase 3 SYNCHRONIZE-1 trial, participants with obesity or overweight treated with Survodutide achieved up to 16.6% mean weight loss over 76 weeks.
- New analyses showed Survodutide reduced visceral fat by up to 34% and liver fat by up to 63.1%, suggesting benefits beyond overall weight reduction.
- The majority of weight loss came from fat mass, with analyses indicating that lean body mass was largely maintained.
- In people with obesity or overweight and metabolic dysfunction-associated steatotic liver disease (MASLD), around 60% of participants achieved normalization of liver fat levels.
Although newer obesity medications have transformed weight management, weight loss alone may not fully capture improvements in health.
For example, the medications may aim to help with fat loss, but growing evidence suggests that weight loss drugs may also reduce skeletal muscle mass, which could lead to adverse effects, such as sarcopenic obesity.
Survodutide is a dual glucagon and glucagon‐like peptide‐1 (GLP‐1) receptor agonist, developed by biopharmaceutical company Boehringer Ingelheim.
By also activating glucagon receptors, the drug aims to increase energy expenditure and influence fat metabolism, while still reducing appetite and food intake. As such, the drug may produce broader metabolic benefits than weight loss alone.
The 76-week phase 3 SYNCHRONIZE-1 trial evaluated Survodutide in 725 adults with obesity or overweight, without type 2 diabetes.
Participants received a weekly injection of Survodutide at either a 3.6 milligram (mg) or 6mg dose, or placebo.
The results show substantial and sustained weight loss, with participants using Survodutide losing up to 16.6% of body weight, without compromising muscle mass, compared with 3.2% in the placebo group.
In a sub-study of the trial involving individuals who provided MRI measurements at baseline and at the end of the study, the results show reductions in visceral fat of up to 34%, and that lean mass accounted for no more than a 10.8% change in total tissue mass, indicating that weight loss was primarily driven by reductions in fat mass.
Additionally, in the same sub-study, the researchers also observed liver fat reductions of up to 63.1%, highlighting that Survodutide could also be beneficial for liver health in those living with obesity.
Carel le Roux, MBChB, FRCP, FRCPath, PhD, Professor at University College in Dublin, Ireland, and Global Coordinating Investigator of the SYNCHRONIZE-1 trial, spoke to Medical News Today about the findings.
“The most important finding from SYNCHRONIZE-1 was the evidence of targeted weight loss, with substantial reductions in metabolically harmful visceral and liver fat alongside preservation of lean mass, highlighting survodutide’s potential to improve broader metabolic health.”
– Carel le Roux, MBChB, FRCP, FRCPath, PhD
“While survodutide demonstrated statistically significant and sustained weight loss over 76 weeks – with up to 16.6% average weight loss versus 3.2% with placebo – the MRI substudy provided important insight into how this weight loss was achieved,” added le Roux.
“The data showed that weight reduction was driven predominantly by fat mass loss, with lean mass accounting for only a small proportion of total tissue mass change. In particular, survodutide reduced visceral fat by up to 34% and liver fat by up to 63.1%, suggesting the potential to address key drivers of metabolic dysfunction associated with obesity,” he detailed.
The 48-week SYNCHRONIZE-MASLD study enrolled 216 adults with obesity or overweight who also had MASLD, with and without type 2 diabetes. Participants received either weekly Survodutide injections of varying doses or a placebo.
The results show that up to 84.2% of participants treated with Survodutide were able to reduce their liver fat by at least 30%, while only 24% of those given the placebo had the same outcome.
Additionally, roughly six out of 10 individuals using Survodutide reduced the amount of fat in their liver to normal ranges after 48 weeks, compared with 5.7% on placebo. Those given Survodutide also lost an average of 12% of their body weight, compared with 1% on placebo.
The researchers also note they observed improvements in liver-related biomarkers, suggesting a reduction in inflammation.
The obesity treatment landscape has become increasingly competitive, with several GLP-1–based therapies already approved for obesity and diabetes.
Survodutide differs from other GLP-1 drugs because it is a dual agonist that combines GLP-1 activity with glucagon receptor activation. The researchers suggest this mechanism may help explain the drug’s apparent effects on visceral and liver fat.
Its GLP-1 activity helps reduce appetite and increase feelings of fullness, while also activating glucagon receptors in the liver. This increases the liver’s ability to reduce fat buildup, improve metabolism, decrease inflammation, and reduce fibrosis.
MASLD is closely tied to metabolic health, type 2 diabetes, and obesity, and is estimated to affect roughly 1 in 3 adults. While standard GLP-1 drugs can help treat MASLD, dual glucagon and GLP‐1 receptor agonist drugs such as Survodutide may offer a more effective option.
However, direct comparisons between Survodutide and other obesity medications have not been conducted in head-to-head trials, making it difficult to determine which therapy is superior.
“Survodutide’s dual glucagon and GLP-1 receptor agonism is designed to address obesity and metabolic dysfunction through complementary mechanisms,” le Roux told MNT. “Its GLP-1 activity helps reduce appetite while increasing fullness and satiety, supporting sustained weight loss.”
“At the same time, the glucagon component is thought to directly impact the liver and metabolic pathways involved in hepatic fat metabolism,” he added. “Based on preclinical and clinical evidence to date, the glucagon agonism may contribute to reductions in liver fat, improvements in metabolic regulation, and potentially inflammation and fibrosis-related pathways.”
“This mechanism is aligned with the reductions in visceral and hepatic fat observed in the SYNCHRONIZE-1 MRI substudy. We think this liver-directed component is an important differentiator for survodutide,” le Roux explained.
“While currently available GLP-1-based treatments primarily focus on appetite regulation and weight reduction, survodutide’s dual agonism is specifically designed to directly impact the liver — a key regulator of metabolic function,” he detailed.
“However, any comparisons with other therapies should be made cautiously, as cross-trial comparisons are limited by differences in study designs, populations, and endpoints,” the researcher pointed out.
As with other drugs in the GLP-1 class, gastrointestinal side effects are an important consideration. Symptoms such as nausea, vomiting, and diarrhea were the most common adverse events.
Additionally, one in five participants discontinued treatment due to side effects, a rate higher than that in the placebo group.
The researchers note that many of these events occurred during dose escalation and were generally classified as mild to moderate.
While the results are promising, Survodutide remains an investigational therapy and has not yet received regulatory approval for obesity or liver disease.
“The reductions in visceral and liver fat are clinically meaningful because these fat depots are strongly associated with cardiometabolic disease risk, including MASLD/MASH, type 2 diabetes, and cardiovascular disease,” explained le Roux.
“Visceral fat and hepatic fat are considered particularly harmful forms of fat due to their links with inflammation and metabolic dysfunction. As mentioned, in SYNCHRONIZE-1, the MRI substudy showed up to a 34% reduction in visceral fat and up to a 63.1% reduction in liver fat after 76 weeks of treatment,” he continued.
“These findings go beyond overall weight reduction and indicate a potentially targeted effect on metabolically harmful fat stores. The liver fat findings are especially notable because up to 75% of people living with obesity may also have MASLD. Reducing hepatic fat may help improve metabolic health and preserve liver function, which is why these data are considered highly relevant in the broader context of obesity and connected diseases.”
– Carel le Roux, MBChB, FRCP, FRCPath, PhD
As part of the SYNCHRONIZE program, Survodutide is also under evaluation in other global phase 3 studies. This includes SYNCHRONIZE-2, investigating the drug in those living with obesity who also have type 2 diabetes, and SYNCHRONIZE-CVOT, which is testing the Effect of Survodutide on cardiovascular safety in those with overweight or obesity.
If future studies confirm the current findings, Survodutide could emerge as a treatment that addresses multiple aspects of metabolic disease simultaneously, such as obesity, excess visceral fat, and fatty liver disease, rather than focusing solely on body weight reduction.
