Episode Details

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This is the final in a three-part series about Tirzepatide (Brand name Mounjaro for Type 2 diabetes and Zepbound for Weight Loss.) In part one we discussed the basics of the drug, in part 2 we discussed the authors of this study and finally, in part three we’ll finish discussing the most recent study on Zepbound - SURMOUNT -4.

(the text in italics is from the study itself.)

SURMOUNT-4 was designed to find out what happens when higher-weight people (without type 2 diabetes) go on the drug for a while and then go off of it. The study was divided into two periods In the first 36 weeks all of the participants took Tirzepatide. Then there was a 52-week period during which subjects were randomly assigned to receive either tirzepatide, or a placebo.

The basic findings, per the study:

After 36 weeks of open-label maximum tolerated dose of tirzepatide (10 or 15 mg), adults (n = 670) with obesity or overweight (without diabetes) experienced a mean weight reduction of 20.9%. From randomization (at week 36), those switched to placebo experienced a 14% weight regain and those continuing tirzepatide experienced an additional 5.5% weight reduction during the 52-week double-blind period.

Here's a graph that shows the average results:

Some things to note:

First, the graph clearly shows that people who go off the drug rapidly start regaining the weight they lost, and their weight was trending up when follow-up ended, suggesting that the weight regain will continue (as we’ve seen in about a century of research and in the history of weight loss drugs.) In addition to being exposed to the side effects of these drugs (some of which can be fatal) these people will also be subjected to the risks that come from weight cycling which include everything from increased risk of type 2 diabetes and hypertension to increased cardiovascular disease and overall mortality. This is important since there are any number of reasons why someone would have to go off the drug, from side effects, to expense, to availability.

For those who remained on the drug, weight loss slowed considerably and by the end, had started to rise slightly, which means that the claim that weight loss will be permanent as long as people stay on the drug is not supported by the evidence.

Let’s go beyond average results and get into some specifics - 783 participants were enrolled in the initial 36-week study in which all participants took Tirzepatide, but 113 discontinued the study drug before the 36-week stage even ended, most commonly due to an adverse event or participant withdrawal. So a little over 14% didn’t even make it 9 months on the drug, and that’s including the fact that the drug was started at a minimal 2.5mg dose and then increased by 2.5 mg every 4 weeks until a maximum tolerated dose of 10 or 15 mg was achieved.

300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period

Did you catch that? First, 10.5% of the group who were still taking the drug during the one-year follow-up had already gained back mor