Research by Austin Graybeal ’21 Ph.D., assistant professor of kinesiology in Texas Christian University’s Harris College of Nursing & Health Sciences, was recently published. But his work on GLP-1 medications and the link between muscle loss and fat began back during his time as a doctoral student at TCU, stemming from his dissertation, when he led an early group raising the question of GLP-1 medications and muscle loss (termed fat-free mass loss), several months before the first GLP-1 medication was FDA approved specifically for weight loss.

He recently took time with TCU News to answer a few questions about his research.

Can you start by explaining what happens in the body with both fat and muscle when taking GLP-1s?
GLP-1 medications, an umbrella term commonly used for the newer generation of weight-loss drugs such as Wegovy, Ozempic, Zepbound, Mounjaro and Foundayo, work largely by curbing appetite. They increase feelings of fullness, slow how quickly food leaves the stomach, and help regulate blood sugar. They do this by mimicking or enhancing the actions of hormones such as glucagon-like peptide-1 (i.e., GLP-1), but with a much more powerful and sustained effect than our naturally occurring GLP-1 alone.

That mechanism is particularly important for people struggling with their weight, as research suggests that obesity can be associated with impaired appetite responses after eating. In other words, the biological signals telling someone that they have eaten enough may not be as effective as they should be. These medications can help restore or amplify those signals.

The result is that people eat less and lose weight, which is unsurprising. But there is a trade-off: the food you stop eating also contains the nutrients your body needs to maintain muscle, which is one of the tissues most closely tied to lifelong health, physical function and independence.

Fortunately, we have learned a lot since then, and the good news is that most of the weight being lost is fat. However, any substantial or rapid weight loss, whether it occurs through medication, dieting or bariatric surgery, typically takes some lean tissue along with the fat. That does not mean we should avoid the weight loss; it means we need to plan for it. Preserving muscle helps maintain strength, supports metabolic health and allows us to remain functional and independent as we age.

Are certain people more at risk for losing muscle mass or is this a risk or side effect for everyone?
Most people who lose a meaningful-to-substantial amount of weight will lose at least some lean tissue, so to some degree this is relevant to everyone. But that loss is not necessarily distributed evenly.

In our study, women and people who began treatment at a higher body weight experienced some of the largest changes. They lost the most fat, which is encouraging, but they also tended to lose more muscle in relative terms. In other words, some of the people seeing the most dramatic benefits may also be the people who most need to prioritize protecting their lean tissue. These can also be populations that, on average, have lower relative protein intake, lower participation in resistance training, or less confidence navigating exercise and nutrition.

There is another dimension that goes beyond muscle itself and has become a major focus of our lab. Women make up roughly two-thirds of GLP-1 users, and for many people, the body can change faster than the mind adjusts to that change. When weight comes off very quickly, someone's self-image may struggle to keep pace. In some cases, that disconnect could encourage overly restrictive eating, which can further increase the risk of losing muscle. We are now studying the crossover between rapid physical change and body image because we think it is an underappreciated part of the risk framework, particularly for women and for people who have lived with obesity for a long time.

So, if people are taking GLP-1 medication, what can they do to protect their muscle mass while losing fat?
Two things consistently stand out in the research, and they really go hand-in-hand. The first is eating enough protein, which provides the nutrients the body needs to maintain muscle during weight loss. The second is regular resistance training, whether that means lifting weights, using resistance machines or performing body-weight exercises. Resistance training provides the stimulus that signals the body, even while weight is coming down, that muscle is still needed and should be preserved, and the protein supports that preservation.

In our study, everyone received diet and exercise counseling alongside the medication. I think that combination is an important part of why our results were as positive as they were from a muscle-preservation standpoint, and it may help explain why some people have very different experiences while taking these medications. I would frame the medication as a powerful tool, but one that is not meant to carry the entire load by itself. The medication and the lifestyle are meant to work together.

I would also encourage people, when possible, to monitor their body composition rather than focusing exclusively on the amount of weight lost, ideally in partnership with their care team. Body weight tells you how much you've changed, body composition tells you what you've changed. For long-term health, that distinction may be more important.

Is there anything else readers should know?
I want to make sure people don't interpret this research as a cautionary tale about these medications. GLP-1 therapies are genuinely effective, and for many people they have accomplished what decades of other approaches could not. The goal of our research is not to scare anyone away from these medications. It is to understand how we can help people get the benefits of treatment while also preserving their strength, function and relationship with their body.

The last thing I would emphasize is that the people who often have the most to gain from strength training and good nutrition are sometimes the people least likely to feel comfortable or welcome pursuing them. That may be because of intimidation in a gym, limited experience with resistance training or pressure from unrealistic body-image ideals. That is exactly why support, good information and a strong care team matter so much.

Of course, anyone considering or currently taking these medications should make those decisions with their own healthcare provider. Our work is meant to better inform that conversation, not replace it.