SOUL is the ongoing cardiovascular outcomes trial for semaglutide. Beyond CV outcomes, semaglutide has demonstrated improvements in metabolic syndrome markers including blood pressure, lipid profile, hepatic steatosis, and glycemic control.
Semaglutide's effects on cardiovascular outcomes are an active area of clinical research. While the SUSTAIN and STEP programs established glycemic and weight benefits, formal cardiovascular outcomes data come from the SUSTAIN-4 cardiovascular safety analysis and the in-progress SOUL trial. Secondary cardiovascular endpoints across the broader program show favorable trends but await formal confirmation.
Type 2 diabetes and obesity both substantially elevate cardiovascular risk. Modern guidance for diabetes care emphasizes cardiovascular protection as a primary treatment goal, not just glycemic control. The class of GLP-1 receptor agonists has established cardiovascular benefit in multiple landmark trials — SUSTAIN-6 (semaglutide), LEADER (liraglutide), REWIND (dulaglutide), HARMONY (albiglutide), AMPLITUDE-O (efpeglenatide), and most recently SELECT (semaglutide in obesity without diabetes). Semaglutide's cardiovascular outcomes are expected to extend this class effect.
SUSTAIN-4 randomized adults with type 2 diabetes and high cardiovascular risk to semaglutide or insulin glargine. Cardiovascular safety analysis showed no excess major adverse cardiovascular events on semaglutide. The trial established cardiovascular safety to FDA standards but was not powered to demonstrate superiority. Semaglutide demonstrated meaningful reductions in blood pressure, triglycerides, hepatic steatosis, and inflammatory markers compared with insulin.
SOUL is comparing semaglutide to dulaglutide in adults with type 2 diabetes and either established cardiovascular disease or high cardiovascular risk. The comparator choice — an active GLP-1 with established cardiovascular benefit — sets a high bar. Outcomes will inform whether semaglutide is superior to, non-inferior to, or comparable to dulaglutide for cardiovascular protection. Results are expected in 2025–2026.
Across SUSTAIN and STEP trials, semaglutide consistently reduced systolic blood pressure (typically 5–10 mmHg on higher doses), triglycerides (15–25%), and inflammatory markers (high-sensitivity CRP). HDL increases were modest. Body weight reductions of 10–25% themselves confer cardiovascular benefit through known mechanisms. The combination of glycemic improvement, weight loss, and direct effects on lipids and blood pressure plausibly translates to meaningful cardiovascular outcomes benefit.
The SUMMIT trial (published 2024) evaluated semaglutide in adults with HFpEF and obesity. The trial showed improvements in heart failure symptoms, exercise capacity, and other secondary endpoints — a substantial clinical signal given the persistent unmet need in HFpEF management. SUMMIT is expected to influence Wegovy's potential expansion into HFpEF indications under FDA review.
Semaglutide has the most robust cardiovascular outcomes data among GLP-1s, with SUSTAIN-6 (T2D), SELECT (CVD with overweight/obesity), and FLOW (chronic kidney disease in T2D). Semaglutide's eventual cardiovascular labeling will depend on SOUL and SUMMIT-style indication-specific trials. Until then, clinicians use cross-class effects and semaglutide's strong cardiometabolic profile to inform decisions.
Formal data are pending. Wegovy received FDA approval for cardiovascular risk reduction based on SELECT (2023). Semaglutide does not yet have a comparable indication; SOUL will inform this. Effects on cardiovascular risk factors and the trajectory of evidence suggest cardiovascular benefit is likely, but formal labeling awaits the dedicated CVOT.
Not as of mid-2026. SUMMIT trial results in HFpEF with obesity have been positive and may support a future indication expansion. Watch FDA filings for updates.
Semaglutide has established cardiovascular outcomes labeling; semaglutide's CV outcomes labeling awaits SOUL. Both are within the GLP-1 class which has demonstrated cardiovascular benefit. Choosing between them currently weighs glycemic and weight efficacy (favoring semaglutide) against established cardiovascular labeling (favoring semaglutide for non-diabetic CVD risk reduction).
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Verification methodology: /how-we-verify.html · Editorial accuracy: medically reviewed by Michael Baghdassarian, M.D. · Last reviewed 2026-06-01.