Survodutide CVOT Tests CV Safety of Dual Agonist: Biykem Bozkurt, MD, PhD

Establishing cardiovascular safety was essential for survodutide (Boehringer Ingelheim), a novel glucagon and glucagon-like peptide-1 (GLP-1) dual receptor agonist, said Biykem Bozkurt, MD, PhD, professor of medicine and senior dean of faculty at Baylor College of Medicine, and principal investigator of the SYNCHRONIZE-CVOT trial (NCT06077864). She discussed the rationale for the phase 3 SYNCHRONIZE-CVOT trial, the first global cardiovascular safety trial of the class.

Why Obesity Calls for Cardiometabolic Treatment

“Obesity is a complex chronic disease involving multiple biological pathways, including abnormalities in energy metabolism, visceral and dysfunctional fat accumulation, insulin resistance, inflammation,” Bozkurt said. These pathways contribute to diabetes, hyperlipidemia, hypertension, chronic kidney disease, and cardiovascular disease, which is a leading cause of death among individuals living with obesity.

Therapies must therefore address risk beyond weight reduction. “It’s not just the magnitude of weight loss; it’s the quality of weight loss,” she said.

Survodutide is designed based on an endogenous peptide. GLP-1 receptor agonism promotes satiety, improves glucose control, and reduces weight. Glucagon receptor activation adds complementary effects by enhancing hepatic lipid metabolism, fatty acid oxidation, and energy expenditure.

Why a Noninferiority Outcomes Trial was Needed

“Given the novelty of this new therapeutic class…and potential direct effects of glucagon on the cardiovascular system, establishing cardiovascular safety through a non-inferiority outcomes trial was essential,” Bozkurt said.

The trial aimed to determine whether the dual agonist can be used safely in patients at elevated cardiovascular risk. That includes individuals living with obesity, with or without diabetes, who have established cardiovascular disease or chronic kidney disease, including patients with coronary artery disease, myocardial infarction, or heart failure.

“Glucagon has complex physiological effects, including potential effects on cardiovascular function as well as glucose metabolism, and we needed to demonstrate this safety along with its effects on the comprehensive cardiovascular benefits,” she said. Those findings were presented at the American Heart Association (AHA) Scientific Sessions 2026 and simultaneously published in The Lancet.¹

References

1. Bozkurt B, le Roux CW, Wharton S, et al. Cardiovascular outcomes with survodutide in adults with obesity at increased cardiovascular risk (SYNCHRONIZE-CVOT): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. Published online November 9, 2026. doi:10.1016/S0140-6736(26)02140-9