Novo Nordisk Secures First Oral GLP-1 Cardiovascular Approval in EU

Novo Nordisk’s Rybelsus® (oral semaglutide) has now become the first and only oral GLP-1 receptor agonist (GLP-1 RA) approved in Europe with proven cardiovascular benefit, following updated CHMP labeling. The decision is grounded in the SOUL phase 3b trial, which demonstrated a 14% reduction in major adverse cardiovascular events (MACE: CV death, MI, stroke) in high-risk type 2 diabetes patients.

This milestone signals more than just an incremental label expansion—it positions oral semaglutide as a differentiated asset within the crowded GLP-1 space, with implications across treatment algorithms, market access, and future competitive strategy.

The SOUL Data: What Sets Oral Semaglutide Apart

• Design: 9,650-patient global outcomes trial; double-blind, placebo-controlled.
• Population: T2D patients with established ASCVD and/or CKD.
• Result: 14% relative risk reduction in MACE, consistent across BMI and weight subgroups.
• Secondary insights: Reduced hospitalisations for serious adverse events.

These findings elevate oral semaglutide beyond its glycaemic and weight-reduction profile, anchoring it firmly in the cardiovascular outcomes space traditionally dominated by injectables.

Strategic Implications

1. Oral Convenience + Outcomes Data = New Standard?
Injectable GLP-1 RAs (Ozempic, Trulicity, Mounjaro) already have strong CV outcome data. But Rybelsus now brings those benefits into pill form—removing the injection barrier that still limits uptake in some populations. This could re-set prescribing behavior, especially for early-stage patients or in markets where injection hesitancy is strong.

2. Competitive Pressures in the Oral GLP-1 Race
So far, Novo Nordisk owns the oral GLP-1 category. Competitors (Lilly, Pfizer) have oral incretin programs, but none with outcomes data at this stage. The SOUL results lock in a first-mover advantage, potentially extending Novo’s leadership for years.

3. Market Expansion Beyond Diabetes
In parallel, Novo is pursuing US approval for oral Wegovy® (25 mg semaglutide pill) for obesity + CV risk reduction. If successful, Novo will replicate the same playbook in obesity that it has now executed in diabetes: show outcomes benefit, win regulatory label, and secure payer adoption.

4. Access and Pricing Considerations
GLP-1 demand already outstrips supply. Oral formulations may ease logistics, but payer negotiations around cardiovascular outcomes benefit will determine uptake speed. Expect differential adoption: faster in Europe (where outcomes data is heavily weighted), slower in cost-sensitive markets.

Relevance for China

• Rybelsus is already marketed in China for type 2 diabetes. A CV label would meaningfully strengthen its case for inclusion and expansion in reimbursement lists, where outcomes evidence often drives policy.
• Patient adherence: Oral format may resonate strongly in China’s outpatient setting, where injection reluctance remains a barrier.
• Local competition: Chinese firms are advancing GLP-1 and dual agonist pipelines, but no domestic oral GLP-1 with CV outcomes data is close to market. Novo’s lead could widen the competitive moat.

Takeaway

With this EU approval, Novo Nordisk has effectively repositioned oral semaglutide as a cardiovascular drug in addition to a diabetes therapy. This reframing matters: it allows payers to justify broader use, patients to overcome needle resistance, and prescribers to treat earlier.

The GLP-1 market has been defined by injectables with outcomes data. With Rybelsus, that paradigm is shifting toward oral therapies that deliver equivalent cardiovascular protection. For Novo Nordisk, it’s not just a label change—it’s a strategic moat that competitors will struggle to breach in the short term.

Reference

Novo Nordisk Press Release ID 916425: “EU approval makes Novo Nordisk’s oral semaglutide the first and only oral GLP-1 RA to reduce cardiovascular death, heart attack and stroke.” 15 September 2025.