Ingelheim am Rhein, Germany, November 9, 2026
Boehringer Ingelheim has announced positive results from its global Phase III SYNCHRONIZE-CVOT clinical trial, demonstrating a favorable cardiovascular safety profile for investigational survodutide in adults living with overweight or obesity and elevated cardiovascular risk. The study met its primary endpoint, showing that survodutide did not increase the risk of major adverse cardiovascular events (MACE) compared with placebo. The findings were presented at the American Heart Association (AHA) Scientific Sessions 2026 in Chicago, Illinois, and simultaneously published in The Lancet on November 9, 2026. Survodutide (BI 456906) is an investigational dual glucagon and glucagon-like peptide-1 (GLP-1) receptor agonist designed to address metabolic dysfunction through two complementary biological pathways. In addition to demonstrating cardiovascular safety, the treatment showed improvements in several cardiometabolic measures, including systolic blood pressure, waist circumference, body weight and metabolic biomarkers. These findings add important evidence to the clinical development of survodutide as a potential treatment for obesity and related metabolic complications.
Phase III Trial Meets Cardiovascular Safety Endpoint
The Phase III SYNCHRONIZE-CVOT trial was a randomized, double-blind, placebo-controlled cardiovascular outcomes study involving 5,530 adults with overweight or obesity and established cardiovascular disease, chronic kidney disease, and/or multiple weight-related complications or cardiovascular risk factors. Participants received once-weekly injections of survodutide at doses of 3.6 mg or 6.0 mg, or placebo. The primary endpoint evaluated the time to the first occurrence of a composite of five major cardiovascular events, including cardiovascular death, non-fatal heart attack, non-fatal stroke, coronary revascularization and heart failure events. The results showed a hazard ratio of 0.89 (95% confidence interval: 0.67–1.18) for survodutide compared with placebo. The study met its predefined non-inferiority criterion, with a p-value below 0.0001 using the treatment-regimen estimand. This demonstrates that survodutide did not increase the risk of these major cardiovascular events compared with placebo in the studied population. A key secondary analysis of three-point MACE, comprising cardiovascular death, non-fatal heart attack and non-fatal stroke, also met its non-inferiority criterion, with a hazard ratio of 0.84. Importantly, the findings establish cardiovascular safety within the trial’s statistical framework, not cardiovascular superiority or a proven reduction in cardiovascular events.
Improvements in Weight and Cardiometabolic Health
Beyond cardiovascular safety, survodutide demonstrated improvements across several important measures of metabolic health at Week 72. The supplementary secondary estimand, which estimates treatment effects assuming continued treatment, showed a reduction in systolic blood pressure of up to 6.68 mmHg, compared with 1.76 mmHg in the placebo group. Waist circumference decreased by up to 11.96 cm, compared with 2.74 cm with placebo. The treatment also produced weight loss of up to 13.7%, compared with 2.0% in the placebo group, in the studied population that included individuals with type 2 diabetes. Additional improvements were reported in high-sensitivity C-reactive protein (hs-CRP), an inflammatory biomarker, and triglycerides, which are associated with cardiometabolic risk. These findings are relevant because obesity is linked to several interconnected health conditions, including type 2 diabetes, cardiovascular disease, chronic kidney disease and metabolic dysfunction-associated steatotic liver disease. The results suggest that survodutide may have potential benefits extending beyond body-weight reduction. However, the magnitude of these changes should be interpreted in the context of the specific trial analysis and estimand used, rather than as guaranteed outcomes for individual patients.
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Dual Receptor Approach Advances MASH Research
Survodutide activates both GLP-1 and glucagon receptors, which play complementary roles in metabolic regulation. GLP-1 receptor activation helps regulate appetite and energy intake, while glucagon receptor activation is associated with effects on energy expenditure and liver metabolism. By targeting both pathways, Boehringer Ingelheim aims to address multiple aspects of metabolic dysfunction associated with obesity. The company also reported that gastrointestinal adverse events, particularly nausea, vomiting, diarrhea and constipation, were the most commonly observed side effects and were generally mild to moderate. Discontinuation rates due to gastrointestinal adverse events were 19.3% with the 3.6 mg dose and 20.8% with the 6.0 mg dose, compared with 1.9% in the placebo group. These findings highlight the importance of dose escalation and treatment tolerability in future development. Survodutide is also being investigated in Phase III LIVERAGE studies for patients with MASH and liver fibrosis. Following the broader SYNCHRONIZE clinical program, Boehringer Ingelheim stated that it is moving forward with global regulatory submissions for survodutide in obesity. The candidate remains investigational and has not been approved for use; its safety and efficacy have not yet been established by regulatory authorities.
Source: Boehringer Ingelheim press release
