The differences are not clinically or statistically significant across trials. That's good! It means there's likely not any excess wasting from taking today's wonder drug. But lean body mass isn't exactly what we're interested in, is it? Lean body mass includes more than muscle.

Thankfully, we now have high-quality MRI-based evidence that GLP-1RAs do not reduce muscle mass beyond what's expected from equivalent non-pharmacological weight loss. This new evidence actually leverages the U.K. Biobank study.

The way this works is simple. You take people randomized to the GLP-1 receptor agonist drug Tirzepatide and compare them to a matched cohort who lost weight without pharmacological assistance in the U.K. Biobank. The correlation between weight and lean loss is similar in both:

But correlation shmorrelation, what if the intercepts differ even though the slopes are so alike? Glad you asked. Because there's no difference in muscle volume loss.

But, you may ask, even though muscle isn't excessively lost with GLP-1 drugs, what about muscle quality? As it turns out, muscle quality as indexed by the amount of fat infiltrating it improves even more with GLP-1s than with normal weight loss!

Muscle quality as indexed by reported physical functioning also improves. Moreover, among those who have had bariatric surgery--which we now know produces comparable weight loss--their relative strength goes up and they become more physically capable.

In short: There is no reason to think that GLP-1 drugs are make people relatively fatter (they reliably increase the ratio of muscle to fat), more fat than they would be doing something else (no difference), or weaker than they would be losing weight in another way.

If you'd like to know more, check out my latest article. It's all about this topic: https://www.cremieux.xyz/p/oze...