Apple, Pear, and Orange

A Sketchy Head-to-Head Study of Tirzepatide and Semaglutide

The headline is compelling. “Zepbound outperforms Ozempic and Wegovy in head-to-head weight loss study.” It certainly confirms the bias of a lot of people in the field. But is it true? Did tirzepatide (Zepbound) really beat semaglutide (Wegovy) in a head-to-head comparative study for obesity? In a word, no.

Uncontrolled, Observational, and Inequivalent Dosing

The LA Times says this is “the first head-to-head comparison of two blockbuster drugs used in real-world conditions.” That phrase points to the limitations of this comparison. It was an observational study based on electronic patient records. More concerning, though, the investigators did not have solid data on the doses patients received. They explain:

“We relied on brand as a proxy for target dose. The standard full dose is 0.5 mg for semaglutide labeled for T2D and 5.0 mg for tirzepatide (labeled exclusively for T2D at the time of this analysis).”

But the approved dose for obesity with semaglutide is 2.4 mg – not 0.5 mg. On average it takes more semaglutide to get the full therapeutic effect on body weight than is required merely for control of diabetes. The same is not true for tirzepatide. Doses used for diabetes are exactly the same as doses used for obesity in the case of tirzepatide.

These researchers chose to compare Mounjaro to Ozempic for weight management. Thus, we can be pretty confident that most of the patients in the semaglutide group received suboptimal doses for weight loss.

Read with Caution

So really, this is not a head-to-head comparison of tirzepatide and semaglutide for weight loss. Rather, it is a comparison of real world weight outcomes when treating diabetes with these two drugs. In that setting, the side effect of weight loss with semaglutide is less.

Sweeping generalizations about one or the other drug being better therefore can be misleading. Different people have different needs and will have different experiences. Results may vary is boilerplate for a reason.

As a side note, this study does give us interesting insight about dropout from therapy with these two drugs. In the 12 months of the study, a little more than half of patients stopped taking either drug. For tirzepatide, it was 56%. The number for semaglutide was 53%. The authors note:

“Additional research on discontinuation is needed, including the role of shortages, adverse events, and costs.

More to Come

Finally, we will likely get a more definitive answer about the relative efficacy of tirzepatide versus semaglutide purely for obesity from an RCT that is due to be complete in November. Given that tirzepatide’s maker, Lilly, is spending a tidy sum of money on this study, the odds are good that it will be favorable for tirzepatide. Not because the results are rigged, but because these are smart people choosing to do a study from which they have good reasons to expect favorable results.

Click here for the study, here and here for further reporting on it.

Apple, Pear, and Orange; painting by Gustave Courbet / Wikimedia Commons

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July 10, 2024

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