Survodutide: A Dual GLP-1/Glucagon Agonist Reshaping Cardiometabolic Care.

Survodutide shows promise for significant weight loss and glycemic control, but higher discontinuation rates due to side effects raise concerns about its long-term use.

Summary and findings

Survodutide is a dual glucagon and GLP-1 receptor agonist evaluated for its effects on cardiometabolic conditions. Phase 2 trials reported weight loss up to 18.7% and HbA1c reductions of up to -1.71%. The ongoing SYNCHRONIZE-CVOT trial aims to assess its impact on cardiovascular events and long-term safety.

Abstract

Cardiovascular disease remains the leading cause of mortality worldwide, with obesity, type 2 diabetes, and metabolic dysfunction-associated steatohepatitis (MASH) serving as major upstream drivers. Current therapies largely address downstream risk factors, leaving a need for agents that modify the metabolic contributors to cardiovascular disease. Survodutide, a dual glucagon and glucagon-like peptide-1 receptor agonist, represents an emerging therapy with broad metabolic effects, including potent weight reduction, glycemic control, hepatic fat reduction, and anti-inflammatory activity. Phase 2 trials have demonstrated weight loss up to 18.7% and HbA1c reductions up to -1.71%, outperforming semaglutide for weight outcomes while maintaining comparable glycemic efficacy. In MASH, survodutide achieved significant improvements in liver fat and fibrosis, offering potential cardiovascular protection through reductions in systemic inflammation and fibrosis-related remodeling. Its mechanistic profile suggests benefits for visceral and epicardial adiposity, with implications for heart failure with preserved ejection fraction. Early signals of renal benefit further underscore its role in cardiorenal syndromes. Adverse events, primarily gastrointestinal intolerance and modest heart rate increases, remain important limitations, contributing to discontinuation rates higher than comparator agents. The ongoing Survodutide for the treatment of obesity study (SYNCHRONIZE-CVOT) trial will clarify whether these robust metabolic effects translate into reduced cardiovascular events and long-term safety. Survodutide has the potential to reshape cardiometabolic care by addressing multiple converging pathways that drive cardiovascular disease. Confirmation of its safety and efficacy in outcomes trials could establish dual agonism as a cornerstone therapeutic strategy for patients with obesity, type 2 diabetes, MASH, and cardiorenal disease.

Limitations

Not reported in abstract.

Elsewhere in the Survodutide (BI 456906) corpus