Roads of Mljet to Gudauri

What Comes from 88 Weeks of Tirzepatide? Or Stopping It?

NB: An earlier version of this post reflected confusion of time periods in this study. We regret the error.
“The long run is a misleading guide to current affairs. In the long run we are all dead,“ wrote John Maynard Keynes. But Keynes was obviously not a doctor. So his words don’t hold much sway over people who have questions about obesity medicines with impressive short-term results. But for those people, a new study in JAMA this week brings useful insights about what happens after 88 weeks of tirzepatide for obesity.

After a little less than two years of treatment with tirzepatide, people lost, on average, 25% of their body weight. For anyone who is familiar with studies of obesity medicine – or metabolic surgery – this is an impressive outcome.

But perhaps even more interesting is the observation that most people who stop after 36  weeks don’t regain all of the weight they lost in those first eight months. On average, a year after stopping the drug, they still weighed ten percent less than they did when they started.

Tirzepatide comes with two different brand names for the same drug: Mounjaro for diabetes and Zepbound for obesity. The difference? Marketing and labeling.

Placebo Controlled and Double Blinded

This is truly an impressive study. A total of 783 persons started on three years of tirzepatide for obesity. At the end of 36 weeks, 670 of them were randomized to receive either continuing therapy with tirzepatide or a week placebo injection. Of the starting group, 113 individuals had dropped out by the 36-week mark for a variety of reasons, including adverse events.

We note that from the time of randomization to the completion of 88 weeks, twice as many people withdrew from the placebo group as withdrew from tirzepatide. Perhaps some of the people getting weekly injections of a placebo figured out that it wasn’t helping them.

Why Didn’t Placebo Patients Regain Everything?

Clearly, this study shows the benefits of ongoing therapy with tirzepatide. People kept losing weight after 36 weeks on this drug and enjoyed significant benefits in cardiometabolic health.

But we also have much to learn from the fact that people who switched over to placebo did not regain all of the weight they had lost – even a year later. Are these “legacy effects” of tirzepatide? Or did lifestyle therapy play a role? Lead author Louis Aronne tells us that these are important questions to answer.

So, yes, ongoing therapy with tirzepatide is clearly beneficial. And still, we have much to learn about chronic care for this chronic disease.

Click here for the new study, here and here for further perspective on it.

Roads of Mljet to Gudauri, painting by Ivan Aivazovsky / WikiArt

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December 13, 2023