Survodutide clears cardiovascular safety bar in Phase 3 SYNCHRONIZE-CVOT

The glucagon/GLP-1 dual agonist met its primary MACE non-inferiority endpoint in 5,530 high-risk adults, with cardiometabolic benefits published simultaneously in

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Zealand Pharma and Boehringer Ingelheim have reported that survodutide, a dual glucagon/GLP-1 receptor agonist, demonstrated a favourable cardiovascular safety profile in the Phase 3 SYNCHRONIZE-CVOT trial, the first cardiovascular outcomes trial (CVOT) conducted for a drug of this mechanistic class. Full results were presented at the American Heart Association Scientific Sessions in Chicago on 9 November 2026 and published simultaneously in The Lancet.

The trial enrolled 5,530 adults living with obesity or overweight who also had established cardiovascular disease, chronic kidney disease, or at least two weight-related risk factors for CVD. Participants received weekly subcutaneous injections of survodutide at either 3.6 mg or 6.0 mg, or placebo, over 72 weeks. The primary composite endpoint, a five-point major adverse cardiovascular event (5P-MACE) measure covering cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularisation, and heart failure events, was met for non-inferiority against placebo, with a hazard ratio of 0.89 (95% CI: 0.67–1.18; p less than 0.0001 for non-inferiority using the treatment-regimen estimand).

Cardiometabolic benefits beyond safety

Beyond the primary safety read, survodutide produced several meaningful secondary improvements. Systolic blood pressure fell by up to 6.68 mmHg in the survodutide arm versus 1.76 mmHg with placebo at 72 weeks (p=0.0001), and waist circumference reduced by up to 11.96 cm versus 2.74 cm for placebo, a marker closely associated with visceral fat burden and cardiometabolic risk. The drug also delivered weight loss of up to 13.7% at week 72 against 2.0% for placebo, in a population that included patients with type 2 diabetes. Additional reductions were observed in high-sensitivity C-reactive protein and triglycerides, both established cardiovascular risk biomarkers.

David Kendall, Chief Medical Officer at Zealand Pharma, said the totality of data across the SYNCHRONIZE programme, which also includes SYNCHRONIZE-1, SYNCHRONIZE-2, and SYNCHRONIZE-MASLD, gives the partnership confidence that "dual glucagon/GLP-1 can significantly reduce body weight, improve glycaemic control, reduce liver fat and favourably affects cardiovascular risk factors." Boehringer Ingelheim has indicated it is proceeding with global regulatory submissions for survodutide in obesity.

Gastrointestinal adverse events were the most common tolerability issue, consistent with the GLP-1 drug class. Treatment discontinuation due to GI events reached 19.3% and 20.8% at the 3.6 mg and 6.0 mg doses respectively, compared with 1.9% in the placebo arm, rates the companies attributed partly to limited dose-titration flexibility in the original SYNCHRONIZE-CVOT protocol. Forthcoming Phase 3b studies, including SYNCHRONIZE-START and SYNCHRONIZE-HERA, are designed with more flexible titration strategies to improve real-world tolerability.

Competitive and regulatory context

The obesity therapeutics market has been reshaped by GLP-1-based agents, most notably semaglutide and tirzepatide, both of which have established CVOTs underpinning their cardiovascular benefit claims. Survodutide's glucagon co-agonism is designed to add incremental effects on energy expenditure and hepatic metabolism beyond what a pure GLP-1 agonist achieves, a differentiation story that will be tested against established competitors during regulatory review.

For Zealand Pharma, which licensed survodutide to Boehringer Ingelheim and receives milestones and royalties on its commercialisation, the CVOT readout completes the registrational evidence package for the obesity indication. Survodutide is also in Phase 3 development for metabolic dysfunction-associated steatohepatitis (MASH), where it holds FDA Breakthrough Therapy designation and EMA PRIME status, a parallel indication that could meaningfully broaden its commercial profile if regulatory submissions are successful. The next key milestone for the programme will be regulatory agency responses to the obesity filings Boehringer Ingelheim has indicated are under way.

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