The biggest argument against using GLP-1s for weight loss is that they cause excess muscle loss. But as it turns out... GLP-1s do not cause any more muscle loss than traditional weight loss methods! Let's discuss🧵

The differences in weight loss in that chart showing data from different trials are not 1. Clinically significant—they're not large enough to matter physiologically 2. Statistically significant—each weight loss method is not distinguishable in current data But that's lean mass

Lean mass includes water. Unfortunately, if we use DXA scans to understand body composition, we include that with muscle. But if we use MRIs, we can separate water and muscle! As it turns out, the UK Biobank has just the required data.

The way this analysis works is simple. You take people randomized to the GLP-1 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:

We can also see that tirzepatide-based loss is indistinguishable from typical weight loss, with no difference in muscle volume loss noted.

Additionally, by using MRI data, you can investigate questions of muscle quality as indexed by how much fat 'infiltrates' muscle. In fact, with tirzepatide, there's a marked reduction in fat infiltration, so it seems to improve muscle quality!

Added bonus: people report improved physical functioning despite overall losing muscle (a natural part of losing weight).

Since that data came out, more meta-analyses on this subject have been conducted. Their results are exciting! Now we know, more confidently, that weight loss with GLP-1RA drugs produces very similar lean mass losses to traditional weight loss.

There are even new trial results like BELIEVE (results shown), EMBRAZE, and COURAGE that are specifically concerned with muscle mass loss, and they show... The same hopeful results! And they show some other drugs that might help improve weight loss composition more generally.

These findings are so replicable that I've even been able to replicate them with subscriber-submitted data. Among more than 400 of my subscribers who sent in DXA data, I found that weight loss on GLP-1RAs was very similar to traditional weight loss, and with exercise, better.

I could go on with even more evidence in this thread, but that's what the article linked below is for, so I won't. What I'll say is this: - GLP-1RAs don't destroy excess muscle - GLP-1RAs don't excessively reduce the metabolic rate - GLP-1RAs work via CICO This is what we know