Novo Nordisk’s Wegovy® (semaglutide) and Eli Lilly’s Mounjaro (tirzepatide) are two incretin-based therapies used widely in obesity and diabetes treatment. Both have shown strong effects on weight loss and metabolic health, but new data highlight important differences in heart outcomes.

At the European Society of Cardiology (ESC) Congress 2025, Novo Nordisk reported that Wegovy® (semaglutide 2.4 mg) cut the risk of heart attack, stroke, or death by 57% compared with Mounjaro in people with obesity and established cardiovascular disease (CVD) who remained on treatment. In the broader population, including those with treatment gaps, Wegovy® still showed a 29% reduction.

The STEER real-world study builds on earlier SELECT results and supports the view that semaglutide’s cardiovascular benefit is molecule-specific, rather than a general feature of GLP-1 or GIP/GLP-1 drugs.

The results follow closely after Lilly’s SURPASS-CVOT trial, which compared Mounjaro with Trulicity in people with type 2 diabetes and CVD. That study confirmed non-inferiority, showing an 8% lower risk of major adverse cardiovascular events (MACE), defined as cardiovascular death, heart attack, or stroke, but without statistical superiority. Mounjaro’s key strengths were stronger reductions in weight, A1C, and kidney function decline, as well as a 16% lower rate of all-cause death.

How Lilly’s Results Add Context

• Lilly proved that Mounjaro is not inferior to Trulicity in diabetes patients with CVD, but it did not reach superiority for MACE. Its strengths are metabolic, with better weight, glucose, and kidney outcomes.
• Novo Nordisk followed by showing Wegovy outperforms Mounjaro directly in real-world obesity with CVD patients without diabetes, suggesting the heart-protective effect is stronger and more molecule-specific.

In other words:

• Lilly demonstrated that tirzepatide is safe and competitive in diabetes.
• Novo Nordisk then used head-to-head real-world data to argue semaglutide is distinctly better for cardiovascular protection in obesity.

Sources

Novo Nordisk Press Release
Mounjaro Shows Heart Health Potential in Landmark Diabetes Trial

Update

Since this report, additional studies and expert commentary have added context:

• HFpEF study: In people with obesity and type 2 diabetes, semaglutide and tirzepatide showed similar benefits for heart failure with preserved ejection fraction.
• Expert reaction: Clinicians welcomed the STEER findings but cautioned that, as real-world data, they should be viewed as hypothesis-generating until confirmed in randomized trials.
• Mechanistic research: New lab studies suggest GLP-1 drugs may directly improve blood flow in the heart’s smallest vessels, pointing to cardiovascular effects beyond weight loss.

The conversation around GLP-1 therapies and heart health is still evolving. Future studies should help answer the questions that have come up.

Further Reading

• New Study: GLP-1 Drugs Protect the Heart, And It Has Nothing to Do with Weight Loss - On The Pen
• New CV outcomes signal: Semaglutide vs Tirzepatide - Michael Albert, MD
• Wait, what?!?!? - Conan Tu, MD
• It’s hard to imagine - Beverly Tchang, MD
• This study fuels the critical conversation - Robert Gabbay, MD, PhD
• How long before we see robust RCTs to validate these signals? - Robert Gabbay, MD, PhD
• Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction - JAMA