ZEPBOUND/MOUNJARO AND WEGOVY FACE OFF!

Hot off the presses in the New England Journal of Medicine and presented simultaneously at the European Congress of Obesity this week are the results of a head-to-head trial comparing tirzepatide (Zepbound/Mounjaro) to semaglutide (Wegovy) for weight loss. (Coincidentally, tirzepatide for weight management (Zepbound) was just approved in Canada yesterday – stay tuned for more on this in another blog post!)

The SURMOUNT-5 trial was an open label trial (meaning participants and the study teams knew what they were taking) that randomized 751 adults with obesity (BMI 27 or higher) to receive either maximum tolerated dose of tirzepatide (10mg or 15mg weekly) vs maximum tolerated dose of semaglutide (1.7mg or 2.4mg weekly). At 72 weeks, weight loss was 20.2% with tirzepatide vs 13.7% with semaglutide. People in the tirzepatide group lost an average of 18.4cm (7.2 inches) from their waist, vs 13cm (5.1 inches) with semaglutide. While both groups had benefits to cardiovascular risk factors like blood pressure, blood sugar, and cholesterol, the benefits were greater with tirzepatide.

Women lost about 6% more weight than men with both treatments. (We often see more weight loss success in obesity medicine clinical trials in women than men, though we don’t know why that is.)

I was really interested to learn about gastrointestinal (GI) side effects in this head-to-head comparison. Before I tell you their findings, here’s the background: A previous study of tirzepatide 5mg, 10mg, and 15mg weekly vs semaglutide 1mg weekly in people with type 2 diabetes found a little more GI side effects with tirzepatide. But in clinical practice, doctors around the world (including myself) have noticed that people who don’t tolerate semaglutide well often tolerate tirzepatide well.

The SURMOUNT 5 study found that while nausea, diarrhea, and constipation were about the same on either medication, there was a little more vomiting with semaglutide (21.3% of participants) vs tirzepatide (15%). Though the need to stop medication due to GI side effects was low for both groups, it was a little higher with semaglutide (5.6%) than tirzepatide (2.7%). Here I will point out that if a person in this study couldn’t tolerate at least 10mg of tirzepatide or at least 1.7mg of semaglutide due to GI side effects, they were required by the study protocol to stop treatment entirely. This differs from clinical practice where we may try to see if a lower dose would be tolerated. There were more injection site reactions with tirzepatide (8.6%) than semaglutide (0.3%).

So it’s clear from the SURMOUNT-5 study that tirzepatide (Zepbound/Mounjaro) provides greater weight loss than semaglutide (Wegovy). Does that mean that tirzepatide is the choice medication? My answer to that is entirely dependent on the health and the goals of the individual person sitting in front of me. What treatment goals matter to that person? What weight-related health issues does that person have? Both medications have shown benefits in numerous weight-related health conditions, and we should recommend treatment tailored towards improving the weight-related health issues that each individual carries. Both medications provide meaningful and robust weight loss. If a particular weight target is important to that person, and that target fits best with a medication providing greater weight loss, then we may go with that treatment.

You may wonder – isn’t more weight loss always better? While we do tend to see greater improvements to weight-related health issues with greater weight loss, at a certain point (which will be different for each person), more weight loss may not be better. For example, a person may have reached their health goals without needing more weight loss. Also, some people may be at risk of losing too much weight, which can be prevented by increasing the dose more slowly, using less than the maximum dose, and/or decreasing the dose as needed. Finally, remember that the response to weight loss medication varies greatly from one individual to the next – again, it’s about individualizing treatment and dosage to find what works best for that person’s holistic care.

BOTTOM LINE: Tirzepatide (Zepbound/Mounjaro) provides greater weight loss than semaglutide (Wegovy), though both medications provide robust and clinically important weight loss benefits. In choosing the best weight management medication for each individual (be that one of these two treatments, or another medication entirely), the choice should be aligned with the targets of treatment set by each individual with their health care team – be that tailoring treatment to the proven benefit to that person’s weight-related health issues, and/or numbers on the scale (if that is important to the person being treated).

Disclaimer: I am an investigator in clinical trials of tirzepatide and semaglutide. I receive honoraria as a continuing medical education speaker and consultant from the makers of tirzepatide (Eli Lilly) and semaglutide (Novo Nordisk).

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