Do You Lose More Muscle with GLP-1 Weight Loss Medications? The Science Behind Muscle Mass and Obesity Drugs

Written by Dr. Ritva Mettänen, MD

The media is full of alarming reports about the “side effects” of GLP-1 medications. If you've been following the news, you’ve probably seen more fear than facts. It almost seems like the media has taken on the role of scaring people away from these medications entirely. Why? Because fear drives clicks — and clicks drive revenue.

But here’s the problem: behind those headlines are real people trying to improve their health, and misinformation isn’t helping anyone.

One of the Most Common Concerns: Muscle Loss

One of the most prominent and heated claims during the spring of 2025 has been that GLP-1 medications cause a greater loss of muscle mass in patients compared to tirzepatide or traditional, non-medical weight loss methods. Understandably, this claim has sparked significant concern among users of obesity medications, causing many to hesitate before starting or continuing treatment.

But Why Does Muscle Mass Matter More Than You Think?

Before we dive into the latest research, let’s quickly revisit what muscles — primarily skeletal muscles —  actually do—beyond making you look fit:

✅ Improve body composition and firmness
✅ Increase strength

But that’s just the beginning. Muscle tissue plays a critical role in overall health:

✅ Helps regulate blood sugar and improves metabolic health
✅ Supports immune function and reduces infection risk
✅ Maintains joint health
✅ Improves balance and coordination
✅ Speeds recovery after illness or surgery

In short: muscle isn’t just for aesthetics—it’s a vital organ system. Okay, so now we definitely know that muscle really matters.

What Does the Science Say About Muscle Loss and GLP-1 Medications?

I know what scared you—that one study claiming that up to 40% of the weight lost by GLP-1-RA users came from muscle mass. But that was just one study, okay? It’s important to understand that the scientific world is not infallible. Confirming any finding or hypothesis requires multiple peer-reviewed studies. In more recent studies published after that one, this alarming claim about massive muscle loss has been debunked.

The latest researches suggests that the degree of muscle loss may not be as substantial as initially feared. For example, newer research shows that the ratio of fat mass lost to lean mass lost when using GLP-1 medications is actually similar to that seen in people losing weight through lifestyle changes or even surgery—about 25% lean mass, regardless of the method used.

In a 72-week study where tirzepatide (a combination of GLP-1 and GIP) was used as the weight loss drug, participants’ muscle mass was measured using DXA—the gold standard in body composition analysis. The study showed that the percentage of lean mass lost was exactly the same — 25% — in both the tirzepatide and placebo groups.And here’s another key point: lean mass is not the same as muscle mass.

It’s also important to understand that lean mass ≠ muscle mass. Lean body mass includes everything in the body that isn’t fat—organs, bones, water, etc. Skeletal muscle makes up just over 50% of lean mass, meaning not all lean mass loss is muscle.

So, Will You Lose More Muscle with Obesity Medications Like GLP-1?

The short answer is no, you won’t. GLP-1 medications do not cause you to lose significantly more muscle than other weight loss approaches. But that doesn’t mean you should start skipping leg day just because weight loss feels easier with the help of these injections.

Because the truth is, if you rely solely on the jabs and do nothing else, this is going to be just another temporary diet—and you're unlikely to see lasting results.

And I’m pretty sure that’s not what you want.

The good news? You can and should preserve your muscle mass—and it all starts with one simple, proven action: resistance training.

So, What Determines How Much Muscle We Lose During Weight Loss?

The most important factor is the speed of weight loss. And the second most important factor is resistance training.

I get it—everyone wants fast and impressive results. But this approach comes at a cost. The more weight you lose per week, the higher the proportion of that loss is lean mass—not fat tissue.

Rapid weight loss is neither healthy nor recommended. In fact, it can completely disrupt your body’s natural balance:

• Thyroid function may suffer
• Nutrient deficiencies can lead to hair loss, iron deficiency, brittle nails, fatigue, and overall weakness

So what’s the right pace for sustainable and muscle-preserving weight loss?

(Drumroll, please...)

0.5–1 kg per week.
And not a gram more.

Your body also remembers everything: the amount of muscle and fat it once had. And it will always try to return to that baseline. The more muscle you lose, the more fat you regain. That’s why the less muscle you lose during weight loss, the better — for both your metabolism and long-term results.

So, ladies and gentlemen:
Lift the weights. Don’t skip leg day. Your future self will thank you.

How to Protect — and Build — Muscle Mass

Considering that muscle mass decreases by about 3–8% per decade after age 30 — and that rate increases as we age — it’s crucial to take care of your muscles. The sooner you start taking care of your muscles, the better the results.

This is especially important for women, as menopause accelerates metabolic changes starting around age 40, leading to not only muscle loss but also bone weakening.

Current research shows that the best way to maintain and build muscle tissue is through resistance training.

Not just protein.
Not just cardio.
But resistance training.

Combining aerobic exercise and sufficient protein intake with weight training takes a bit more effort—but it’s absolutely worth it.

What if I’m using weight loss jabs, you may ask. The more resistance training you include, the less muscle you lose. So, no excuses!

Want to read more? Scroll down and enjoy!

A Deeper Dive To Muscles And Health

Blood Sugar Control

Muscles are the most important target for insulin and blood glucose.
When you eat a meal, your blood sugar rises. High blood sugar isn’t good for your body, so it needs to be quickly transported to a safe place where it can’t do harm.

Think of glucose as a tipsy friend on a Friday night: it needs a ride home. Insulin is the “taxi” that picks it up and drops it off where it belongs.

You’ve probably heard that excess energy gets stored in fat cells (think of these as the sugar’s summer cottages), but did you know that muscle cells are glucose’s true home? And insulin doesn’t just act as a taxi — it also rings the doorbell (the insulin receptor) to let each sugar molecule into the cell (home). If the glucose isn’t used right away, it’s stored in the muscle cells as glycogen.

Immune System Support

Wait, what?! What do muscles have to do with immunity?
Oh, a lot. Muscle cells and the immune system are closely linked.

Muscle cells contain important immune-supporting white blood cells and interleukins like IL-6 and IL-15, which have significant anti-inflammatory roles.

Low muscle mass is associated with higher disease risk, while people who maintain muscle mass—especially those who regularly do resistance training—have a reduced risk of infections and metabolic diseases.

In fact, one study found that consistent resistance training reduced the 10-year risk of heart disease by up to 81%.

That’s not a typo.

Joint Health and Longevity

Strong muscles support joint function, which is especially important for weight-bearing joints.

For example, the knees rely on surrounding muscle support to maintain proper movement patterns, stay correctly aligned both at rest and in motion, and reduce joint pain.

And no — you don’t need to be overweight to need this support. Everyone benefits from it.

Strong muscles can also help delay the onset of osteoarthritis and joint degeneration by providing all the benefits just mentioned.

Balance and Fall Prevention

The brain receives signals about our body’s position from three sources: the eyes, the inner ear's balance system, and the muscles. Skeletal muscles contain proprioceptors (balance receptors) — specialized sensors help the brain understand your body’s position and motion.

This is a major reason why older people have a higher risk of falling. We lose 3–8%, even up to 10% of muscle mass per decade. And the less you develop and maintain your muscles, the faster you lose them.

By the time menopause sets in, you’ll start noticing the impact of muscle loss:

• Weight gain
• Rising blood sugar
• Declining physical performance
• Hello, prediabetes

...and so on.

Still wondering if resistance training is optional? It’s not.
It’s a non-negotiable. A lifeline.

Resources:
https://doi.org/10.2337/dci23-0100
https://doi.org/10.1136/jech-2019-212268
https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.16275
DOI: 10.1016/S2213-8587(24)00272-9