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 builds on previously announced positive topline results from SYNCHRONIZE-1 76-week trial, which met its primary endpoints and showed up to 16.6% weight loss with survodutide, a novel glucagon/GLP-1 dual agonist, from baseline.1 ​
• Detailed pre-specified analysis from a sub study of SYNCHRONIZE-1 show that, relative to baseline, survodutide achieved a reduction of up to 34% in visceral fat, with the proportion of lean mass loss reflecting no more than 10.8% of change in total tissue mass at the highest dose, alongside an up to 63.1% reduction of liver fat, indicating a targeted reduction in metabolically harmful fat after 76 weeks.2,3
• Detailed results presented from SYNCHRONIZE-MASLD, showed that the trial met both its primary endpoints, with additional results showing that, relative to baseline, liver fat normalization was reached by 6 out of 10 participants living with metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity or overweight who were treated with survodutide after 48 weeks.4
• The SYNCHRONIZE-1 and SYNCHRONIZE-MASLD results were presented at the American Diabetes Association's (ADA) 2026 Scientific Sessions and simultaneously published in The New England Journal of Medicine and Nature Medicine, respectively.5,6

Ingelheim, Germany - Boehringer Ingelheim today announced positive results from two global Phase III trials of its glucagon/GLP-1 dual agonist survodutide (BI 456906), SYNCHRONIZE-1 and SYNCHRONIZE-MASLD.2,4 The results demonstrate survodutide's potential to reduce weight and therefore improve metabolic health in two distinct populations: adults living with obesity or overweight, without type 2 diabetes (SYNCHRONIZE-1),2 and adults with overweight or obesity with metabolic dysfunction-associated steatotic liver disease (MASLD) with evidence of inflammation and or fibrosis (SYNCHRONIZE-MASLD).4 Full results from SYNCHRONIZE-1 and SYNCHRONIZE-MASLD were presented today at the American Diabetes Association's (ADA) 2026 Scientific Sessions and published simultaneously in The New England Journal of Medicine and Nature Medicine respectively.5,6

SYNCHRONIZE-1 Results

The 76-week Phase III SYNCHRONIZE-1 trial investigated survodutide in adults living with obesity or overweight, without type 2 diabetes. Positive topline data announced in April showed that the trial met its primary endpoints using both the treatment-regimen* and efficacy† estimands.1 Sustained weight loss of up to an average of 16.6% was seen using the efficacy estimand, a statistically significant decrease versus 3.2% in the placebo arm (p<0.0001).2‡ 

In a sub study of the trial the fat loss observed in the patients who provided MRI measurements at baseline and end of study while on treatment, showed a relative reduction of up to 34.0% visceral fat.2 Additional analysis showed that lean mass accounted for no more than 10.8% of change in total tissue mass at the highest dose, indicating that weight loss was primarily driven by reductions in fat mass.2 In the same sub study, a pre-specified analysis showed adults treated with survodutide had liver fat reduction of up to 63.1% further demonstrating survodutide's potential to positively impact metabolic health.2 

“For people living with obesity, weight loss is only one part of the story. They face an increased risk of developing serious conditions driven by obesity and associated metabolic dysfunction, including metabolic liver disease, type 2 diabetes, and cardiovascular disease. There is an urgent need for treatments that go beyond weight loss to also address these related conditions,” Dr Lee Kaplan, M.D., Ph.D., Director of The Obesity and Metabolism Institute, Boston, MA, USA, Chair of the SYNCHRONIZE program executive committee said. “I am delighted to see that these data reveal that the glucagon/GLP-1 dual agonism of survodutide offers a promising approach for people with obesity, and for those with obesity-associated metabolic liver diseases including MASLD and MASH.”   

“Obesity is a complex disease linked to how the body manages metabolism. Excess visceral fat, which is found primarily around the abdomen, is a known contributor to metabolic dysfunction and is closely connected to impaired liver function,” said Shashank Deshpande, Chairman of the Board of Managing Directors and Head of Human Pharma, Boehringer Ingelheim. “By tackling obesity alongside visceral fat and liver fat, survodutide has the potential to redefine what a targeted weight management therapy can achieve, as we aim to address key drivers of metabolic dysfunction often associated with obesity.”

Metabolic health refers to how the body processes nutrients and maintains homeostasis.7 As a complex disease, obesity goes beyond weight, having associations with disruptions in metabolic processes.8 Up to three in every four people living with obesity have MASLD, where excess fat builds up in the liver.9 For about one in three people living with obesity, this can advance to a more serious stage called metabolic dysfunction-associated steatohepatitis (MASH), which is characterized by inflammation and liver damage.9 

SYNCHRONIZE-MASLD results

Positive Phase III results from the SYNCHRONIZE-MASLD trial further reinforce survodutide's potential in metabolic health by demonstrating improvements in weight loss and a targeted reduction in liver fat.4 The SYNCHRONIZE-MASLD trial investigated survodutide for 48 weeks among adults with obesity or overweight who had MASLD with evidence of inflammation and or fibrosis, both with and without type 2 diabetes.4 

The trial met its co-primary endpoints using both the treatment-regimen and efficacy estimands, with results showing that up to 84.2% of participants treated with survodutide experienced at least a 30% relative liver fat reduction using the efficacy estimand, a statistically significant improvement over 24.3% in the placebo arm (p<0.0001).4 The trial met its other co-primary endpoint with a relative reduction in body weight of up to 12.2%, using the efficacy estimand versus 1.0% in the placebo arm (p<0.0001).4 Additional detailed results, from a secondary endpoint, showed up to 6 out of 10 patients (61.0%) reached liver fat normalization (liver fat content <5%) at Week 48 using the efficacy estimand, versus 5.7% in the placebo arm.4 

Positive trends were also observed across other secondary endpoints evaluating liver-related biomarkers, such as alanine transaminase (ALT) levels, signaling reduction in inflammation.4 

As expected with GLP-1 based therapies, in SYNCHRONIZE-1 the most commonly reported adverse events for survodutide were gastrointestinal (GI) events, which were mostly mild to moderate in severity and usually occurring during the dose escalation phase.2 The more frequent events included nausea, vomiting, diarrhea, and constipation compared with placebo.2 The treatment discontinuation rates due to GI adverse events were 19% in people treated with survodutide compared to 2.9% on the placebo arm.2 These results were consistent across the SYNCHRONIZE-MASLD trial and with the known class effects. No new safety signals were identified in both trials.4 Looking ahead, Boehringer is committed to helping patients and clinicians make informed decisions through more optimized, patient centered dosing guidance and protocols.

Collectively, SYNCHRONIZE-1 and SYNCHRONIZE-MASLD show the potential benefits of glucagon/GLP-1 dual agonism for people living with obesity and people with MASLD with evidence of inflammation and or fibrosis.2,4,10 Survodutide could address the unmet need for treatment of these conditions as its GLP‑1 agonism decreases appetite while increasing fullness and satiety,11 while its glucagon agonism is thought to directly act on the liver to reduce hepatic fat, regulate metabolic function, resolve inflammation, and improve fibrosis.12,13,14 Survodutide is an investigational agent and has not been approved for use; its efficacy and safety have not been established.

Additionally, as part of the broader evidence program, a set of Phase IIIb studies are being advanced to address key unmet needs in people living with obesity and real-world care. Initiating later this year, SYNCHRONIZE-HERA will evaluate survodutide in women's health; ELEVATE-LIVER will assess the impact of survodutide in the preservation of cardiac function and structure in people living with MASLD or early MASH; and SYNCHRONIZE-START will examine real-world titration approaches, including treatment initiation and switching from GLP-1 RAs, with a focus on tolerability. These efforts complement SYNCHRONIZE-1 and SYNCHRONIZE-MASLD within the broader global Phase III obesity program in overweight and obesity, including key sub-populations.15,16,17,18,19,20 Survodutide is also being studied in two global Phase III clinical trials LIVERAGE and LIVERAGE-Cirrhosis investigating the efficacy and safety of survodutide in adults with MASH and fibrosis stages 2 or 3 and in those with compensated MASH cirrhosis (fibrosis stage 4).21,22 

Notes to editors

About obesity and overweight

In 2016, more than 1.9 billion adults lived with overweight — defined as a body mass index (BMI) of 25 or more.23 Of these, over 650 million were living with obesity — defined as a BMI of 30 or more.23 More than one billion people around the world are living with obesity today (1 in 8 of us) - and by 2030, that number could be more than double what it was in 2010.24 Overweight and obesity are complex chronic conditions involving abnormal or excessive fat accumulation that present a risk to a person's overall health.8

About metabolic dysfunction-associated steatotic liver disease (MASLD)

MASLD is a condition where excess fat builds up in the liver.25 Up to 75% of people living with obesity will develop MASLD and in 1 in 3 of those, this can advance to a more serious stage called metabolic dysfunction-associated steatohepatitis (MASH).9 MASH is characterized by inflammation and liver damage.9 In the U.S., cases of MASH are predicted to rise by 63% between 2015 and 2030, from 16.5 million to 27.0 million cases.26

About survodutide (BI 456906) 

Survodutide is a glucagon/GLP-1 receptor dual agonist that activates both the glucagon and GLP-1 receptors, which play a role in controlling metabolic functions.12,13,14 Survodutide is an investigational agent and has not been approved for use; its efficacy and safety has not been established. It is being evaluated in a robust Phase III clinical development program, including the SYNCHRONIZE studies for people living with overweight or obesity,15,16,17,18,19,20 and the LIVERAGE studies for people living with MASH and fibrosis.21,22

Survodutide has potential to treat adults with non-cirrhotic MASH and moderate or advanced fibrosis (stages 2 or 3) and has been recognized by the U.S. FDA, which granted it: 

• Fast Track designation in May 2021 and;27
• Breakthrough Therapy designation in September 2024.28 

Survodutide's potential to treat adults with MASH and fibrosis has also been recognized by: 

• the European Medicines Agency (EMA), through acceptance to its PRIME scheme in November 2023 and;29
• the Center for Drug Evaluation of China's National Medical Products Administration (NMPA) which granted it Breakthrough Therapy designation in June 2024 and;
• the Taiwan Food and Drug Administration which granted it Breakthrough Designation in September 2024.

Survodutide is licensed to Boehringer Ingelheim from Zealand Pharma, with Boehringer solely responsible for development and commercialization globally. Survodutide is part of Boehringer Ingelheim's research and development portfolio in the cardiovascular, renal and metabolic disease areas.

About the SYNCHRONIZE-1 trial (NCT06066515)

This is a Phase III, double-blind, placebo-controlled 76-week efficacy and safety trial of survodutide among 725 adults living with obesity or overweight, without type 2 diabetes.15 Participants received a weekly injection of survodutide at either a 3.6mg or 6.0mg dose, or placebo.15 The primary endpoints of the trial are the percentage change in body weight from baseline to Week 76, and an achievement of body weight reduction ≥5% from baseline to Week 76.15 

There are 31 secondary endpoints, including, achievement of ≥10, ≥15%, and ≥20% body weight reduction, and absolute changes from baseline to Week 76 in:15 

• Body weight
• Waist circumference
• Blood pressure
• Body Mass Index (BMI)
• Glycosylated hemoglobin A1c (HbA1c)
• Total cholesterol
• Liver fat content  

Body composition sub study endpoints included absolute and relative change in:

• Total fat volume
• Lean body volume
• Visceral fat volume
• Subcutaneous fat volume

About the SYNCHRONIZE-MASLD trial (NCT06309992)

This is a Phase III, double-blind, placebo-controlled 48-week efficacy and safety trial of survodutide among 218 adults living with obesity and overweight and with MASLD with evidence of inflammation and or fibrosis versus placebo.18 

Participants received a weekly injection of a 6.0mg dose of survodutide, or placebo.18 The primary endpoints of the trial are the relative reduction in liver fat content of at least 30% from baseline to Week 48, and the relative change (%) in body weight [kg] from baseline to Week 48.18 

There are 13 secondary endpoints, including:18 

• Absolute and relative change from baseline to Week 48 in liver fat content assessed by MRI.
• Absolute change from baseline to Week 48 in alanine amino transaminase (ALT) [U/L] levels.
• Absolute change from baseline to Week 48 in liver stiffness [kPa] assessed by magnetic resonance elastography (MRE).
• Absolute change in liver volume [mL] from baseline to Week 48 measured using MRI.

About the SYNCHRONIZE program

Survodutide is also being evaluated in two other global Phase III studies for people living with overweight or obesity among key sub-populations. 

• SYNCHRONIZE-2 enrolled a sub-population of adults with type 2 diabetes.16
• SYNCHRONIZE-CVOT enrolled a sub-population of adults with cardiovascular disease, chronic kidney disease, or with risk factors for cardiovascular disease.17

Survodutide is also being explored in two Phase III in-market trials:

• SYNCHRONIZE-JP in Japan and SYNCHRONIZE-CN in China are exploring survodutide for sub-populations of people living with obesity.19,20 SYNCHRONIZE-JP explores the relative change in liver fat and body composition parameters from baseline to Week 76 when treated with survodutide versus placebo, as a secondary endpoint.19

About LIVERAGE and LIVERAGE-Cirrhosis 

LIVERAGE and LIVERAGE-Cirrhosis are global Phase III clinical trials investigating the efficacy and safety of survodutide in adults with MASH and fibrosis stages 2 or 3 and in those with compensated MASH cirrhosis (fibrosis stage 4), respectively.21,22

LIVERAGE will enroll approximately 1,800 adults, and LIVERAGE-Cirrhosis will enroll approximately 1,590 adults. In each trial, participants are randomized to receive weekly injections of either survodutide, reaching a maximum dose of 6 mg, or placebo.21,22 

About Boehringer Ingelheim

Boehringer Ingelheim is a biopharmaceutical company active in both human and animal health. As one of the industry's top investors in research and development, the company focuses on developing innovative therapies that can improve and extend lives in areas of high unmet medical need. Independent since its foundation in 1885, Boehringer takes a long-term perspective, embedding sustainability along the entire value chain. Our approximately 54,300 employees serve over 130 markets to build a healthier and more sustainable tomorrow. Learn more at www.boehringer-ingelheim.com/uk (UK and Ireland) or www.boehringer-ingelheim.com (rest of world).

Boehringer Ingelheim's Intended Audiences Notice 

This press release is issued from our Corporate Headquarters in Ingelheim, Germany and is intended to provide information about our global business. Please be aware that information relating to the approval status and labels of approved products may vary from country to country, and a country-specific press release on this topic may have been issued in the countries where we do business.

* The treatment-regimen estimand is the estimated treatment effect, regardless of whether the patient adheres to the treatment, discontinues, or initiates other therapies
† The efficacy estimand is the estimated treatment effect assuming patients remained on treatment for the entire study duration. 
‡ P-values for efficacy estimand are nominal; they are calculated primarily for descriptive exploration rather than to establish strict, definitive proof of statistical significance

References

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2. Le Roux, CW. "Efficacy and Safety of Survodutide for the Treatment of Obesity in People without Diabetes:  Results from SYNCHRONIZE™-1” Oral presentation at the American Diabetes Association's (ADA) 2026 Scientific Sessions, New Orleans, US. 7 June 2026.
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