Novo Nordisk has secured a European label update for Rybelsus (oral semaglutide) to include cardiovascular risk reduction based on the SOUL outcomes trial, making it the first and only oral GLP-1 receptor agonist in the EU with proven cardiovascular benefit in adults with type 2 diabetes at high cardiovascular risk. SOUL showed a 14% reduction in major adverse cardiovascular events versus placebo on top of standard of care, with additional analyses to be presented at EASD indicating fewer hospitalizations and benefits consistent across body weight strata. In parallel, a US decision on a similar cardiovascular label for Rybelsus is expected later this year, and Novo has a filing pending for a once-daily 25 mg oral semaglutide for obesity and cardiovascular disease in the US.
The strategic question now is whether this turns Rybelsus from a convenience-driven diabetes brand into an outcomes-led therapy that can command priority positioning in treatment algorithms and reimbursement frameworks. Until now, oral semaglutide’s value story has often hinged on needle avoidance and weight loss. With a hard cardiovascular endpoint in hand, Novo can argue that an oral GLP-1 is not just easier to use for needle-averse patients, but clinically consequential in the highest-risk segment of type 2 diabetes.
This matters immediately for patients who have resisted injectables and for primary care, cardiology, and nephrology teams managing complex cardiometabolic profiles. An oral option with cardiovascular benefit could expand uptake among those unlikely to initiate or persist with injections, but Medical Affairs will need to close the adherence gap associated with the fasting administration requirement for Rybelsus and the potential for gastrointestinal intolerance. If the hospitalization reductions highlighted from SOUL translate into real-world settings, that becomes a powerful lever for payer negotiations, particularly in health systems focused on avoiding acute bed-days and downstream costs.
For payers in Europe, the update provides a new basis to revisit access criteria. Several markets tether GLP-1 reimbursement to demonstrated cardiovascular outcomes or restrict access by BMI or prior therapy failure. A cardiovascular indication for an oral GLP-1 could loosen BMI-based restrictions for high-risk diabetics and pull Rybelsus earlier into pathways alongside, not after, SGLT2 inhibitors. Expect pressure for indication-based pricing or outcomes-based agreements as budget holders balance cardiometabolic benefits against rising class spend. For Market Access teams, country-by-country evidence packages connecting SOUL outcomes to local hospitalization and cost offsets will be crucial, as will plans for real-world evidence to confirm persistence and effectiveness with oral dosing in routine care.
Competitionally, Novo gains a first-mover edge in oral incretins with cardiovascular proof. Eli Lilly’s oral orforglipron remains in late-stage development without completed outcomes data, and broader class competition still centers on injectables with strong weight loss and cardiovascular narratives. The label expansion also strengthens Novo’s incretin portfolio coherence across diabetes and obesity; if an oral Wegovy formulation is approved in the US, the company could extend the GLP-1 franchise’s reach into primary care at scale. The limiting factor remains the supply of semaglutide and manufacturing flexibility across dosage forms, which will influence how aggressively commercial teams can pivot from injectable to oral demand.
The next six to twelve months will show whether guidelines, payers, and prescribers treat Rybelsus as a cardiovascular drug that happens to be oral, rather than an oral drug with cardiovascular data. The answer will hinge on real-world adherence, cross-specialty education, and Novo’s ability to translate SOUL into country-specific value stories before rival oral incretins arrive.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
