Survodutide Meets CV Safety End Point in SYNCHRONIZE-CVOT

Survodutide, an investigational glucagon/glucagon-like peptide-1 (GLP-1) receptor dual agonist, did not increase the risk of major adverse cardiovascular events (MACE) compared with placebo in adults with overweight or obesity and elevated cardiovascular risk, according to phase 3 SYNCHRONIZE-CVOT (NCT06077864) results presented at the American Heart Association (AHA) Scientific Sessions 2026 and simultaneously published in The Lancet.¹

Boehringer Ingelheim described the study as the first global cardiovascular safety trial of a glucagon/GLP-1 dual agonist and said it is preparing regulatory submissions for survodutide in obesity based on the full SYNCHRONIZE program.

"For people living with obesity, the clinical challenge extends beyond weight to the profound, often unrecognized effects of obesity on cardiovascular and metabolic health,” said Biykem Bozkurt, MD, PhD, principal investigator of the SYNCHRONIZE-CVOT trial, in a statement. “We are looking at novel therapeutic approaches that do not merely reduce body weight but can also improve metabolic dysfunction while maintaining cardiovascular safety. Combined with the breadth of evidence from the SYNCHRONIZE program, these data help give us confidence in how we could manage obesity and related cardiometabolic risk.”

Survodutide Met Noninferiority for 5-Point MACE

The double-blind, event-driven trial enrolled 5530 adults with obesity or overweight and established cardiovascular disease (CVD), chronic kidney disease, and/or at least 2 weight-related complications or risk factors for CVD. Participants received once-weekly survodutide 3.6 mg, survodutide 6.0 mg, or placebo.

The primary end point was time to first 5-point MACE: cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, ischemia-related coronary revascularization, or heart failure events. Survodutide was noninferior to placebo (HR, 0.89; 95% CI, 0.67-1.18; P < .001 for noninferiority using the treatment-regimen estimand), and the trial met its primary end point under both the treatment-regimen and supplementary secondary estimands.

Results were similar for the key secondary end point of 3-point MACE, a composite of cardiovascular death, nonfatal stroke, or nonfatal MI (HR, 0.84; 95% CI, 0.60-1.18; P < .0001 for noninferiority).

Systolic Blood Pressure Fell by Up to 6.68 mm Hg at 72 Weeks

Using the supplementary secondary estimand, systolic blood pressure decreased by up to 6.68 mm Hg with survodutide vs 1.76 mm Hg with placebo at 72 weeks (P = .0001). Waist circumference, a marker closely linked to visceral fat, decreased by up to 11.96 cm vs 2.74 cm with placebo, and body weight fell by up to 13.7% vs 2.0% in a population that included individuals with type 2 diabetes. Survodutide also significantly reduced high-sensitivity C-reactive protein and triglycerides.

In the earlier phase 3 SYNCHRONIZE-1 trial of 725 adults with obesity without diabetes, published in The New England Journal of Medicine, mean body weight change at week 76 under the treatment-regimen estimand was –12.2% with survodutide 3.6 mg and –13.0% with 6.0 mg vs –5.4% with placebo.² The trials enrolled different populations and reported weight using different estimands, so the figures are not directly comparable.

GI-Related Discontinuations Reached Roughly 20%

Gastrointestinal (GI) events, mostly mild to moderate, were the most commonly reported adverse events in SYNCHRONIZE-CVOT, led by nausea, vomiting, diarrhea, and constipation.¹ Discontinuation due to GI adverse events occurred in 19.3% of participants receiving survodutide 3.6 mg and 20.8% receiving 6.0 mg vs 1.9% with placebo, which the company said is consistent with other SYNCHRONIZE trials.

Discontinuations usually occurred during dose escalation, because the original protocol allowed limited flexibility to slow titration, adjust doses, or extend temporary interruptions. Ongoing and upcoming trials, including SYNCHRONIZE-START, SYNCHRONIZE-HERA, ELEVATE-LIVER, and SYNCHRONIZE-T2D, build in more flexible titration from the start.

Survodutide is not approved for any use. It is also being studied in metabolic dysfunction-associated steatohepatitis (MASH) in the phase 3 LIVERAGE and LIVERAGE-Cirrhosis trials.

"The SYNCHRONIZE-CVOT trial findings represent an important milestone for survodutide clinical development, as this is the first time we have demonstrated survodutide safety with respect to major adverse cardiovascular events,” said Shashank Deshpande, chairman of the board of managing directors and head of human pharma, Boehringer Ingelheim, in a statement. "Together with the growing body of evidence from the SYNCHRONIZE program, these results strengthen our confidence in the potential of survodutide’s dual-agonist approach to address underlying metabolic dysfunction and improve broader metabolic health beyond body weight alone. We remain committed to building evidence across interconnected metabolic diseases through our broader global clinical development program."

References

1. Boehringer Ingelheim's survodutide is the first glucagon/GLP-1 dual agonist to demonstrate a favorable cardiovascular safety profile in global phase 3 SYNCHRONIZE-CVOT trial alongside significant cardiometabolic benefits. News release. Boehringer Ingelheim. November 9, 2026. Accessed November 9, 2026.
2. le Roux CW, Wharton S, Startseva E, et al. Survodutide once weekly for the treatment of adults with obesity. N Engl J Med. Published online June 7, 2026. doi:10.1056/NEJMoa2600751