GLP-1 RAs For Weight Loss (But How Much Of That Loss Is Muscle?)

First introduced as a diabetes medication, GLP-1 drugs quickly took hold for off-label use as weight loss aids, even when the science was still very young.

Here’s one of our first articles on that, back in the day: Semaglutide’s Surprisingly Big Research Gap

As for that popularity? Check out: 1 in 5 US Women Aged 50–64 Has Used GLP-1 RAs: What We’ve Learned

Spoiler, one of the things we’ve learned is: Most People Who Start GLP-1 RAs Quit Them Within A Year (Here’s Why)

One of the main things in their favor is, of course, that (for most people, anyway), they work (except when they don’t: Why Intermittent Fasting (& GLP-1 Drugs!) Might Not Work For You).

But it seems that even that comes with a drawback of its own, and in this case, it’s a drawback that keeps on giving taking.

Wrong weight loss!

Recent research has shown that 25–40% of the weight lost on GLP-1 drugs comes from fat-free mass (mostly muscle), compared to only 8% per decade lost naturally with age.

As we wrote about in an older article of ours:

❝Of the four studies that actually looked at the macros (unlike most studies), they found that on average, protein intake decreased by 17.1%. Which is a big deal!

It’s an especially big deal, because while protein’s obviously important for everyone, it’s especially important for anyone trying to lose weight, because muscle mass is a major factor in metabolic base rate—which in turn is much important for fat loss/maintenance than exercise, when it comes to how many calories we burn by simply existing.

A reasonable hypothesis, therefore, is that one of the numerous reasons people who quit GLP-1 agonists immediately put fat back on, is because they probably lost muscle mass in amongst their weight loss, meaning that their metabolic base rate will have decreased, meaning that they end up more disposed to put on fat than before.❞

Read in full: Semaglutide’s Surprisingly Big Research Gap ← our older article that we quoted above

And now the very latest research (by Dr. Charlotte Suetta et al.) puts even more weight behind our hypothesis that we wrote about back in the day, and adds new numbers to it.

All incretin-based drugs (GLP-1–related therapies) tested were associated with a higher proportion of muscle loss relative to total weight loss compared with placebo or lifestyle interventions.

As for the numbers: the median proportion of weight loss from muscle-related tissue was 34.9%, with 68% of studies exceeding the 25% benchmark.

Since, as we said, muscle plays a key role in metabolism, glucose regulation, energy expenditure, and immune function, this becomes quite dire, because its loss can keep on self-perpetuating down the line as metabolic health worsens.

In the words of Dr. Suetta herself:

❝Treatment success should not be defined by kilograms lost alone. This is particularly true in older adults and in patients with low muscle reserve or functional limitations.

The question is no longer whether incretin-based therapies reduce body weight; the question now is whether we can ensure that the weight lost is predominantly fat while preserving the muscle needed for metabolic health, physical function and healthy aging.❞

You can find her paper itself, here: Beyond Weight Loss: Preserving Muscle in the Era of Incretin Therapy

As well as a systematic review that found the same: Effect of Incretin-Based and Nonpharmacologic Weight Loss on Body Composition: A Systematic Review

And if you’d prefer to do better, then consider: The 5 Training Rules To Build Your Metabolism (Not Just Lose Weight)

And if you like books, then we highly recommend: Strong: The Definitive Guide To Active Ageing – by Jacqueline Hooton ← The author, herself in her 60s, knows her stuff when it comes to fitness (female fitness in particular) and aging (or: ageing, as you’ll see in this book, with its British English).

Want to learn more?

You might also like this one that we reviewed a little while back:

Magic Pill: The Extraordinary Benefits and Disturbing Risks of the New Weight-Loss Drugs – by Johann Hari

Take care!