ROMA (ITALPRESS) – Boehringer Ingelheim today announced positive results from two global Phase III studies on its dual glucagon/ agonist GLP-1 survodutide (BI 456906): Synchronize-1 and Synchronize-Masld. The results show the potential of survodutide in promoting weight loss and, consequently, improving metabolic health in two distinct populations: adults with obesity or overweight without type 2 diabetes (Synchronize-1), and adults with overweight or obesity affected by steatosic liver disease associated with metabolic dysfunction (Masld) with evidence of inflammation and/or fibrosis (Synchron).
The complete results of the Synchronize-1 and Synchronize-Masld studies were presented today at the Scientific Sessions 2026 of the American Diabetes Association (ADA) and published simultaneously, respectively, on The New England Journal of Medicine and Nature Medicine. The 76-week Phase III Synchronize-1 study assessed suvodutis in adults with obesity or overweight without type 2 diabetes. The positive preliminary data announced in April had already shown the achievement of the primary endpoints using both the therapeutic estimand (treatment-regimen estimand) and the estimand of effectiveness (efficacy estimand). A weight loss sustained up to an average of 16.6% was observed using the estimation of effectiveness, a statistically significant reduction compared to 3.2% observed in the placebo group (p”0,0001).
In a sub-study, in patients who have evaluated by magnetic resonance (MRI) to the basal and at the end of the study during treatment, the observed fat loss showed a relative reduction of visceral fat up to 34.0%. Additional analysis showed that lean mass represented no more than 10.8% of total tissue mass variation at the highest dose, indicating that weight loss was mainly determined by fat mass reduction. In the same sub-study, a pre-specific analysis showed that adults treated with survodutide got a reduction of liver fat up to 63.1%, further confirming the suvodutide potential in improving metabolic health.
“For people living with obesity, weight loss is just a part of history. These individuals face an increased risk of developing severe conditions driven by obesity and associated metabolic dysfunction, including metabolic liver disease, type 2 diabetes and cardiovascular diseases. There is an urgent need for treatments that go beyond simple weight loss and also address these related conditions,” said Lee Kaplan, Director of the Boston Obesity and Metabolism Institute and Chairman of the Executive Committee of the SYNCHRONIZE program.
“I am pleased to see that these data reveal that the dual glucagon/GLP-1 agonism of survodutide offers a promising approach for people with obesity, and for those with metabolic hepatic diseases associated with obesity, including MAS and MASH. Obesity is a complex pathology closely linked to how the body regulates metabolism. Excess visceral fat, located mainly at the abdominal level, is a well-known factor that contributes to metabolic dysfunction and is closely associated with the alteration of liver function”, said Shashank Deshpande, Chairman of the Board of Directors and Head of Human Pharma of Boehringer Ingelheim. “Agendo simultaneously on obesity, visceral fat and liver fat, survodutide has the potential to redefine what a targeted weight management therapy can offer, addressing some of the main factors underlying metabolic dysfunction frequently associated with obesity.”.
Metabolic health refers to the ability of the body to process nutrients and maintain homeostasis. Obesity is a complex pathology that goes beyond the simple excess of body weight and is associated with alterations of metabolic processes. Up to three out of four people with obesity present Masld, a condition in which excess fat accumulates in the liver. In about a three case, the disease can evolve in a more severe form, steatohepatitis associated with metabolic dysfunction (Mash), characterized by inflammation and liver damage. The positive results of Phase III SynchronizE-masld’s study further strengthen the suvodutide potential in improving metabolic health, demonstrating benefits both in weight loss and in the targeted reduction of liver fat.
The study assessed survodutide for 48 weeks in adults with obesity or overweight affecting Masld with evidence of inflammation and/or fibrosis, both with and without type 2 diabetes. The study achieved both primary co-primary endpoints using both therapeutic regime estimation and estimation of effectiveness. The results showed that up to 84.2% of participants treated with survodutide obtained a relative reduction of liver fat equal to at least 30%, according to the estimation of effectiveness, compared to 24,3% observed in the placebo group (p”0,0001). The second co-primary endpoint was also achieved, with a relative reduction of body weight up to 12.2% according to the estimation of effectiveness, compared to 1.0% recorded in the placebo group (p”0,0001).4 Further detailed results related to a secondary endpoint have evidenced that up to 6 out of 10 patients (61.0%) have achieved normalization of liver fat (low liver lipid content of 5%) In addition, favourable trends have been observed in several secondary endpoints related to hepatic biomarkers, including alanine aminotransferase levels (ALT), indicative of a reduction in inflammation.
As envisaged for the therapies based on GLP-1, in the SYNCHRONIZE-1 study, adverse events most commonly reported in patients treated with suvodutis were gastrointestinal (GI), mostly mild or moderate and generally observed during the dose titration phase.2 The most frequent events included nausea, vomiting, diarrhea and constipation, with a greater incidence than the placebo. Treatment interruption rates due to gastrointestinal adverse events amounted to 19% in subjects treated with suvodutide compared to 2.9% in the placebo group. Similar results have been observed in the SYNCHRONIZE-MASLD study and are consistent with the known effects of the therapeutic class. New security signals have not been identified in both studies. Looking to the future, Boehringer confirms his commitment to helping patients and clinicians make informed decisions through increasingly optimized and patient-centered indications and dosing protocols. Together, SYNCHRONIZE-1 and SYNCHRONIZE-MASLD demonstrate the potential benefits of dual glucagon/GLP-1 agonism in people with obesity and in patients with MASLD associated with inflammation and/or fibrosis. Survodutide could respond to the unsatisfied therapeutic need for these conditions, as its agonism of the GLP-1 reduces appetite and increases sense of fullness and satiety, while it is believed that its agonism of the glucagon acts directly on the liver to reduce liver fat content, regulate metabolic function, solve inflammation and improve fibrosis.
Survodutide is an experimental drug and has not been approved for clinical use. Efficacy and safety have not yet been definitively established. In addition, within the broadest program of evidence, a series of Phase IIIb studies are underway to respond to key needs still dissatisfied with people with obesity and real clinical practice. With scheduled start by the end of the year, SYNCHRONIZE- HERA will assess survodutide in female health; ELEVATE-LIVER will assess the impact of survodutide on the preservation of function and heart structure in people with MASLD or MASH in the early stages; and SYNCHRONIZE-START will examine titration approaches in real clinical practice, including the start of treatment and the transition from GLP-1 receptor agonists (GLP-1 RA), with particular attention to tolerance. These initiatives complement the SYNCHRONIZE-1 and SYNCHRONIZE-MASLD studies within the broadest global Phase III programme in obesity and overweight, which includes key subpopulations. Survodutide is also the subject of study in two global Phase III, LIVERAGE and LIVERAGE-Cirrhosis clinical trials, which assess the effectiveness and safety of suvodutide in adults with MASH and stage 2 or 3 fibrosis and in patients with MASH compensated cirrhosis (stadium of fibrosis 4).
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