Novo Nordisk Secures EU Approval for Rybelsus Cardiovascular Benefit Label

European Regulators Endorse Rybelsus for Cardiovascular Risk Reduction

Novo Nordisk A/S (NYSE: NVO) has secured a significant regulatory achievement with the European Medicines Agency's approval to update the label of its oral glucagon-like peptide 1 receptor agonist (GLP-1 RA), Rybelsus (oral semaglutide), to include cardiovascular benefits for patients with type 2 diabetes. This marks a pivotal moment for the drug, positioning it as the first oral GLP-1 RA in the European Union with proven cardiovascular efficacy, bolstering Novo Nordisk's standing in the competitive diabetes treatment landscape.

Clinical Trial Demonstrates Significant Cardiovascular Benefit

The label expansion is predicated on the robust findings from the Phase IIIb SOUL clinical trial. This extensive study, involving 9,650 patients with type 2 diabetes and high cardiovascular risk (atherosclerotic cardiovascular and/or chronic kidney disease), demonstrated that Rybelsus reduced the risk of major adverse cardiovascular events (MACE), including cardiovascular death, heart attack, and stroke, by 14% compared to placebo when added to standard care. This evidence underscores the drug's potential beyond glycemic control, addressing a critical comorbidity in type 2 diabetes.

"Heart problems are the leading cause of disability and death for people living with type 2 diabetes," stated Emil Kongshøj Larsen, executive vice president of International Operations at Novo Nordisk. This highlights the urgent medical need that Rybelsus is now uniquely positioned to address within the oral GLP-1 class in the EU.

Additional data from the SOUL trial also indicated a significant reduction in hospitalizations related to serious adverse events with oral semaglutide. Further detailed results are anticipated to be presented at the European Association for the Study of Diabetes Annual Meeting later this month.

Market Reaction and Competitive Positioning

Following the announcement, Novo Nordisk stock experienced a modest rise in premarket trading, reflecting investor confidence in Rybelsus's expanded market potential. This approval is a strategic win, strengthening Novo Nordisk's competitive edge, particularly against arch-rival Eli Lilly (NYSE: LLY). Eli Lilly's flagship GLP-1 therapies, Mounjaro (for type 2 diabetes) and Zepbound (for obesity), currently lack a cardiovascular indication, offering Rybelsus a distinct advantage in treatment differentiation, especially for patients prioritizing cardiovascular risk reduction. The oral administration of Rybelsus may also enhance patient adherence compared to injectable alternatives, a significant factor in long-term treatment success.

Broader Context and Implications in the GLP-1 Market

The GLP-1 market remains one of the most dynamic and competitive segments in the pharmaceutical industry. While the EU approval is a positive catalyst for Novo Nordisk, the company has faced considerable challenges. Its shares have underperformed, losing approximately 35.3% year-to-date, a stark contrast to the broader pharmaceutical sector. This underperformance is largely attributed to intensifying competition, primarily from Eli Lilly, whose Mounjaro and Zepbound generated a combined $14.7 billion in sales in the first half of 2025, accounting for 52% of Eli Lilly's total revenues. Eli Lilly now leads the U.S. GLP-1 market with a 57% prescription share.

Novo Nordisk's broader strategy involves expanding the label of its semaglutide drugs (including Ozempic and Wegovy) to reach more patient populations and drive incremental revenues. However, the company is also undertaking a significant restructuring, including a workforce reduction, to manage rising costs and adapt to market pressures, as highlighted by its revised operating profit growth estimates for 2025.

The challenges extend to other players in the oral GLP-1 space. Viking Therapeutics (NASDAQ: VKTX) recently reported mixed results for its oral VK2735 formulation, with high discontinuation rates due to adverse events, leading to a substantial 36% to 43% plunge in its stock. This underscores the complexities and high bar for efficacy and tolerability in developing oral GLP-1 treatments, further solidifying Rybelsus's unique position with its established cardiovascular benefit.

Looking Ahead: US Approval and Future Competition

Novo Nordisk is actively pursuing a similar cardiovascular indication label extension for Rybelsus in the United States, with a decision from the Food and Drug Administration (FDA) anticipated later this year. A positive outcome would further solidify Rybelsus's global competitive stance. The company has also submitted a US application for a once-daily 25 mg oral formulation of semaglutide for adults with obesity or overweight and cardiovascular disease, signaling continued innovation and expansion into broader cardiometabolic disease management.

The ongoing competition with Eli Lilly, the potential emergence of generic semaglutide alternatives, and the development of next-generation GLP-1 therapies from companies like Viking Therapeutics will continue to shape the market. Investors will closely monitor regulatory decisions, sales performance, and pipeline developments as Novo Nordisk aims to leverage Rybelsus's enhanced profile to sustain long-term growth and reclaim market momentum.