Boehringer Ingelheim’s Survodutide Phase III Clinical Results: Reduces Visceral Fat by 34% and Liver Fat by 63%, Minimizes Lean Muscle Mass Loss

• This announcement is based on the previously announced positive topline results from the 76-week SYNCHRONIZE-1 study, which met its primary endpoint and showed that the novel glucagon/GLP-1 dual receptor agonist survodutide achieved up to 16.6% weight loss from baseline.¹
• Pre-specified detailed analyses from a substudy of SYNCHRONIZE-1 showed that, compared to baseline, survodutide reduced visceral fat by up to 34%; in the highest dose group, lean body mass loss accounted for no more than 10.8% of total tissue mass change; and liver fat was reduced by up to 63.1%, suggesting targeted reduction of metabolically harmful fat after 76 weeks.^2,3
• Detailed results from the SYNCHRONIZE-MASLD trial showed that the study met both of its primary endpoints. Further results indicated that, compared to baseline, approximately 60% of participants with metabolic dysfunction-associated steatotic liver disease (MASLD) who were overweight or obese achieved normalization of liver fat after 48 weeks of treatment with survodutide.⁴
• The results from SYNCHRONIZE-1 and SYNCHRONIZE-MASLD were presented at the American Diabetes Association (ADA) 2026 Scientific Sessions and published simultaneously in the *New England Journal of Medicine* and *Nature Medicine*, respectively.^5,6

Ingelheim, GermanyJune 8, 2026 /PRNewswire/ — Boehringer Ingelheim today announced positive results from two global Phase III clinical trials, SYNCHRONIZE-1 and SYNCHRONIZE-MASLD, for its glucagon/GLP-1 dual receptor agonist survodutide (BI 456906).^2,4 The results indicate that survodutide has the potential to improve metabolic health through weight loss in two distinct populations: adults with obesity or overweight without type 2 diabetes (SYNCHRONIZE-1),² and adults with MASLD accompanied by inflammation and/or fibrosis who are overweight or obese (SYNCHRONIZE-MASLD).⁴

The complete results from SYNCHRONIZE-1 and SYNCHRONIZE-MASLD were presented today at the American Diabetes Association (ADA) 2026 Scientific Sessions and published simultaneously in the *New England Journal of Medicine* and *Nature Medicine*, respectively.^5,6

SYNCHRONIZE-1 Study Results

The 76-week Phase III SYNCHRONIZE-1 study evaluated the efficacy of survodutide in adults with obesity or overweight without type 2 diabetes. Previously announced topline results in April showed that the study met its primary endpoint under both treatment-regimen* and efficacy† estimand analyses.¹ Based on the efficacy estimand analysis, a mean sustained weight loss of up to 16.6% was observed, which was statistically significant compared to a 3.2% reduction in the placebo group (p＜0.0001).²

In a substudy of this trial, analysis of patients who completed MRI measurements at both baseline and end of study (during treatment) showed a relative reduction in visceral fat of up to 34.0%.² Further analysis indicated that, in the highest dose group, lean body mass loss accounted for no more than 10.8% of total tissue mass change, suggesting that weight loss was primarily driven by fat reduction.² In the same substudy, a pre-specified analysis also showed that adults treated with survodutide experienced a reduction in liver fat of up to 63.1%, further demonstrating its potential to improve metabolic health.²

“For people living with obesity, weight loss only solves part of the problem. They also face an increased risk of serious diseases driven by obesity and related metabolic dysfunction, including metabolic liver disease, type 2 diabetes, and cardiovascular disease. There is an urgent need for treatment options that not only reduce weight but also address these associated conditions,” said Dr. Lee Kaplan, M.D., Ph.D., Director of the Obesity and Metabolism Institute in Boston, USA, and Chair of the SYNCHRONIZE Program Executive Committee. “Encouragingly, these data show that survodutide’s glucagon/GLP-1 dual receptor agonist mechanism offers a promising therapeutic pathway for people with obesity, as well as those with obesity-related metabolic liver disease, including MASLD and MASH.”

“Obesity is a complex disease closely linked to the body’s metabolic regulation. Excess visceral fat, primarily distributed in the abdomen, is a known key driver of metabolic dysfunction and is closely associated with impaired liver function,” said Shashank Deshpande, Chairman of the Executive Board and Head of Human Pharma at Boehringer Ingelheim. “By comprehensively addressing obesity, visceral fat, and liver fat, survodutide has the potential to redefine the possibilities of targeted weight management therapies, aiming to tackle the key drivers of metabolic dysfunction closely linked to obesity.”

Metabolic health refers to the body’s ability to process nutrients and maintain internal homeostasis.⁷ As a complex disease, obesity involves not only weight gain but also disruptions in metabolic processes.⁸ Among people with obesity, up to three-quarters may have concurrent MASLD, characterized by excessive fat accumulation in the liver.⁹ Approximately one-third of people with obesity may progress to the more severe stage of metabolic dysfunction-associated steatohepatitis (MASH), characterized by inflammation and liver damage.⁹

SYNCHRONIZE-MASLD Study Results

The positive results from the Phase III SYNCHRONIZE-MASLD study further reinforce survodutide’s potential in metabolic health, demonstrating targeted reduction of liver fat alongside weight loss.⁴ The study evaluated survodutide over 48 weeks in overweight or non-obese adults with MASLD and evidence of inflammation and/or fibrosis, including participants with or without type 2 diabetes.⁴

The study met its co-primary endpoints under both treatment-regimen and efficacy estimand analyses. Results showed that, in the efficacy estimand analysis, up to 84.2% of participants treated with survodutide achieved at least a 30% relative reduction in liver fat, significantly superior to 24.3% in the placebo group (p＜0.0001).⁴ For the other co-primary endpoint, based on the efficacy estimand analysis, the relative change in body weight from baseline was up to -12.2%, significantly superior to -1.0% in the placebo group (p＜0.0001).⁴ Further detailed results from secondary endpoints showed that at Week 48, up to approximately 60% (61.0%) of patients achieved normalization of liver fat (liver fat content <5%), compared to 5.7% in the placebo group.⁴

Positive trends were also observed in other secondary endpoints assessing liver-related biomarkers, such as improvements in alanine aminotransferase (ALT) levels, suggesting reduced inflammation.⁴

Consistent with the GLP-1 class, the most common adverse events in the SYNCHRONIZE-1 study with survodutide were gastrointestinal (GI) events, mostly mild to moderate and typically occurring during the dose escalation phase.² Compared to placebo, more common adverse events included nausea, vomiting, diarrhea, and constipation.² The discontinuation rate due to GI adverse events was 19%, compared to 2.9% in the placebo group.² These results were consistent in the SYNCHRONIZE-MASLD study and align with the known safety profile of this drug class. No new safety signals were identified in either study.⁴ Looking ahead, Boehringer Ingelheim is committed to optimizing patient-centered dosing guidance and treatment protocols to help patients and clinicians make better treatment decisions.

Overall, the results from SYNCHRONIZE-1 and SYNCHRONIZE-MASLD collectively suggest that the glucagon/GLP-1 dual receptor agonist has the potential to benefit people with obesity, as well as patients with MASLD and evidence of inflammation and/or fibrosis.^2,4,10 Survodutide aims to address unmet treatment needs in these disease areas: its GLP-1 receptor agonism reduces appetite and enhances satiety,¹¹ while its glucagon receptor agonism is thought to act directly on the liver, reducing liver fat, modulating metabolic function, alleviating inflammation, and improving fibrosis.^12,13,14 Survodutide is currently under investigation and has not been approved for clinical use; its efficacy and safety continue to be evaluated.

Additionally, as part of a broader evidence base, several Phase IIIb studies are underway to address key unmet needs in obesity management and real-world clinical practice. These studies are expected to launch later this year: SYNCHRONIZE-HERA will evaluate survodutide in women’s health; ELEVATE-LIVER will assess survodutide’s effects on cardiac function and structure in patients with MASLD or early MASH; and SYNCHRONIZE-START will focus on tolerability, exploring real-world dose escalation strategies, including treatment initiation and switching from GLP-1 receptor agonists. Together with SYNCHRONIZE-1 and SYNCHRONIZE-MASLD, these studies form a key part of the global Phase III obesity research program covering different subpopulations.^{15,16,17,18,19,20}

Meanwhile, survodutide is also being evaluated in two global Phase III studies, LIVERAGE and LIVERAGE-Cirrhosis, targeting adults with MASH and stage 2 or 3 fibrosis, and adults with compensated MASH cirrhosis (stage 4 fibrosis), respectively, to further validate its efficacy and safety.^21,22

About Overweight and Obesity

In 2016, over 1.9 billion adults worldwide were overweight—defined as a body mass index (BMI) ≥25.²³ Of these, over 650 million were living with obesity—defined as a BMI ≥30.²³ Currently, over 1 billion people globally are living with obesity (approximately 1 in 8 people); this number is projected to more than double from 2010 levels by 2030.²⁴ Overweight and obesity are complex chronic diseases characterized by abnormal or excessive fat accumulation that poses a risk to an individual’s overall health.⁸

About Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

MASLD is a condition characterized by excessive fat accumulation in the liver.²⁵ Among people with obesity, up to 75% may develop MASLD; of these, approximately one-third may progress to the more severe stage of metabolic dysfunction-associated steatohepatitis (MASH).⁹ MASH is characterized by liver inflammation and damage.⁹ In the United States, MASH cases are projected to increase by 63% between 2015 and 2030, from 16.5 million to 27 million cases.²⁶

About Survodutide (BI 456906)

Survodutide is a glucagon/GLP-1 dual receptor agonist that simultaneously activates the glucagon receptor and the GLP-1 receptor, both of which play important roles in regulating the body’s metabolic function.^12,13,14

Survodutide is currently under investigation and has not been approved for clinical use; its efficacy and safety have not been established. It is currently being evaluated through a comprehensive Phase III clinical development program, including the SYNCHRONIZE studies for people with overweight or obesity^{15,16,17,18,19,20} and the LIVERAGE studies for people with MASH and accompanying fibrosis.^21,22

Survodutide has shown potential in treating adults with non-cirrhotic MASH and moderate or severe fibrosis (stage 2 or 3) and has received the following designations from the U.S. FDA:

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

Survodutide’s potential in treating adults with MASH and fibrosis has also been recognized by several regulatory agencies:

• Inclusion in the PRIME (Priority Medicines) scheme by the European Medicines Agency (EMA) in November 2023;²⁹
• Breakthrough Therapy designation granted by the Center for Drug Evaluation of China’s National Medical Products Administration (NMPA) in June 2024;
• Breakthrough Therapy designation granted by Taiwan’s Food and Drug Administration in September 2024.

Survodutide is licensed to Boehringer Ingelheim by Zealand Pharma, with Boehringer Ingelheim fully responsible for its global development and commercialization. Survodutide is also a key component of Boehringer Ingelheim’s pipeline in cardiovascular, renal, and metabolic diseases.

This is a Phase III, randomized, double-blind, placebo-controlled 76-week efficacy and safety study involving 725 adults with obesity or overweight without type 2 diabetes, evaluating the efficacy and safety of survodutide.¹⁵ Participants received once-weekly injections of survodutide (at doses of 3.6 mg or 6.0 mg) or placebo.¹⁵ The primary endpoints of the study included:¹⁵ percentage change in body weight from baseline to Week 76, and the proportion of participants achieving ≥5% weight loss from baseline to Week 76. The study included 31 secondary endpoints, including achievement of ≥10%, ≥15%, and ≥20% weight loss, and absolute changes from baseline to Week 76 in:¹⁵

• Body weight
• Waist circumference
• Blood pressure
• Body mass index (BMI)
• Glycated hemoglobin (HbA1c)
• Total cholesterol
• Liver fat content

Additionally, endpoints from a body composition substudy included absolute and relative changes in:

• Total fat volume
• Lean tissue volume
• Visceral fat volume
• Subcutaneous fat volume

This is a Phase III, randomized, double-blind, placebo-controlled 48-week efficacy and safety study involving 218 adults with MASLD and evidence of inflammation and/or fibrosis who are overweight or obese, comparing survodutide with placebo.¹⁸ Participants received once-weekly injections of 6.0 mg survodutide or placebo.¹⁸ The primary endpoints of the study included: relative reduction in liver fat content ≥30% from baseline to Week 48, and percentage change in body weight (kg) from baseline to Week 48.¹⁸

The study also included 13 secondary endpoints, such as:¹⁸

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

About the SYNCHRONIZE Studies

Survodutide is also being evaluated in two additional global Phase III studies targeting key subgroups of people with overweight or obesity:

• SYNCHRONIZE-2: Includes a subgroup of adults with type 2 diabetes.¹⁶
• SYNCHRONIZE-CVOT: Includes a subgroup of adults with cardiovascular disease, chronic kidney disease, or risk factors for cardiovascular disease.¹⁷

Additionally, survodutide is being explored in two Phase III studies in marketed regions:

• SYNCHRONIZE-JP (Japan) and SYNCHRONIZE-CN (China): Evaluating survodutide’s efficacy in specific subgroups of people with obesity.^19,20
• SYNCHRONIZE-JP includes secondary endpoints assessing relative changes in liver fat and body composition parameters from baseline to Week 76 with survodutide compared to placebo.¹⁹

 About the LIVERAGE and LIVERAGE-Cirrhosis Studies

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

LIVERAGE is expected to enroll approximately 1,800 adult participants, and LIVERAGE-Cirrhosis is expected to enroll approximately 1,590 adult participants. In both studies, participants are randomized to receive once-weekly injections of survodutide (up to a maximum dose of 6 mg) or placebo.^21,22

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