Mounjaro vs Wegovy: The First Head-to-Head Trial Reveals a Clear Winner

A major new study has confirmed what many Mounjaro users have long suspected—tirzepatide, the active ingredient in Mounjaro, may deliver greater weight loss than its main rival, Wegovy.

Presented at the European Congress on Obesity and published in the New England Journal of Medicine, the first direct comparison between these two weight-loss drugs has shown Mounjaro led to a 20% average body weight reduction, compared to 14% with Wegovy over 72 weeks.

That’s a difference that’s likely to shape prescribing choices, private sales, and perhaps even NHS pathways in the coming months.

The Numbers Speak Volumes

The trial enrolled 750 people with obesity, all with an average starting weight of 113kg (nearly 18 stone). Each participant was randomly assigned to take the highest tolerated dose of either Mounjaro (tirzepatide) or Wegovy (semaglutide), both self-injected weekly.

The results were striking:

• 32% of Mounjaro users lost 25% or more of their body weight vs 16% with Wegovy
• Mounjaro users saw an average waistline reduction of 18cm, compared to 13cm with Wegovy
• Blood pressure, blood sugar, and cholesterol all improved more significantly with Mounjaro
• Side effects were similar across both groups
• Women tended to lose more weight than men in both arms of the trial

Why the Difference?

Both medications work by mimicking hormones that influence appetite, telling your brain you’re full and slowing down digestion. But Wegovy (semaglutide) activates one hormone pathway, while Mounjaro (tirzepatide) activates two.

This dual-action mechanism appears to be the secret behind Mounjaro’s superior performance. It’s designed not just to suppress appetite but also to increase energy expenditure—essentially encouraging the body to burn more fat while reducing food intake.

Dr Louis Aronne, one of the lead researchers, noted:

“The majority of people with obesity will do just fine with semaglutide (Wegovy), but those at the higher end may ultimately do better with tirzepatide (Mounjaro).”

What Does This Mean for UK Users?

In the UK, both Wegovy and Mounjaro are available through specialist NHS weight-management services, but private demand is booming. According to Prof Naveed Sattar from the University of Glasgow:

“In the UK, tirzepatide sales privately are now well ahead of semaglutide – that’s just a reality – and this paper will accelerate that, I imagine.”

It’s easy to see why. For many patients, a 15% weight loss is life-changing—but if 20–25% is within reach with similar side effects and greater improvements in cardiometabolic health, then Mounjaro becomes the obvious choice.

Wegovy’s Edge: Cardiac Outcomes (for now)

However, it’s not all one-sided. Wegovy already holds a licence in the UK to reduce the risk of heart attacks, based on large cardiovascular trials. Mounjaro hasn’t yet reached that milestone, although similar trials are underway and early signs look promising.

Until those trials are complete, Wegovy may remain the preferred choice for people with a history of cardiovascular events or those looking for additional protective benefits beyond weight loss.

The Bigger Picture: A Rapidly Evolving Field

This trial is just one part of a huge wave of research underway in the field of obesity care. Higher doses, oral versions, and new GLP-1/GIP combinations are already in development. Even novel classes of medications are being tested.

Some experts believe we may be on the cusp of a future where obesity prevention—not just treatment—is possible through medication. Others, like Prof Sattar, remind us that no drug can substitute for societal change:

“It would be far better to make our society healthier to prevent more people developing obesity.”

What This Means for You

If you’re already on Mounjaro, this new trial reinforces what many users have experienced: it works—powerfully, consistently, and across a range of health measures.

If you’re still deciding, or perhaps on Wegovy and considering a switch, it’s worth discussing these findings with your clinician. Both medications have their place, and personalisation is key.

At Life on Mounjaro, we’ll continue to bring you the latest research, real-world stories, and honest reflections from those navigating this journey. Because while the science is evolving, one thing is clear: you deserve options that work for your body, your goals, and your life.

Have you tried Mounjaro or Wegovy?

We’d love to hear from you. Share your story—or just your thoughts—with us by getting in touch.