Does tirzepatide cause muscle loss?

If you’re considering using tirzepatide (Mounjaro or Zepbound) to support weight loss, you may have come across concerns about losing muscle along with body fat. 

So, does tirzepatide cause muscle loss? Yes — though the picture is more nuanced than a simple yes or no. Significant weight loss — whether from tirzepatide or any other method —  can reduce both fat and lean body mass, an umbrella term for muscles, organs, bones, and fluid. However, a substantial portion of the weight lost is typically body fat, and some research suggests muscle quality may improve, meaning the overall body composition may shift in a healthier direction.

Let’s take a closer look at tirzepatide muscle loss, including why it happens, what to do about it, and whether semaglutide vs. tirzepatide is more likely to cause it.

Tirzepatide may cause some muscle loss simply by causing weight loss. Muscle loss is not listed as a side effect of tirzepatide, according to the prescribing information for Zepbound and Mounjaro. But tirzepatide can cause weight loss, and any significant or rapid weight loss can lead to muscle loss. 

Here’s what the science says:

• In clinical trials of tirzepatide, about 25% of the total weight lost came from lean mass, which includes muscle, organs, bones, and body fluids. The majority — roughly 75% — came from fat loss.

• In one study, participants experienced reductions in muscle volume over time. However, these reductions were largely proportional to the amount of weight lost and similar to what’s seen with other weight loss methods.

• In another study, people taking tirzepatide had smaller thigh muscle volume, but they also had significant reductions in fat stored within the muscle. This suggests that some of the change in muscle size may reflect improved muscle quality rather than harmful muscle loss.

Ultimately, even if you lose some muscle on tirzepatide, you may still see an overall improvement in body composition — because most weight loss tends to come from fat rather than muscle.

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Losing a significant amount of weight quickly (whether with tirzepatide or any other method) can lead to muscle loss. People with obesity typically lose about 15% of their body weight on Zepbound, and about 25% of the total weight lost may come from lean mass.

Here are some potential causes of tirzepatide muscle loss:

Weight loss

Weight loss is the main driver of lean body mass loss in people taking tirzepatide. When body weight decreases, both fat and muscle can be lost. Rapid weight loss is even more likely to lead to lean mass loss, which includes muscle.

Wondering how tirzepatide works? As a dual GLP-1 and GIP receptor agonist, tirzepatide mimics two gut hormones that play roles in blood sugar regulation and appetite. Together, these effects slow down digestion, reduce appetite, and quiet cravings — which leads to significant weight loss in many people taking Mounjaro or Zepbound.

Side effects may reduce workout frequency

Fatigue and nausea are two common side effects of tirzepatide. And if you’re feeling tired and sick, you might be tempted to skip your regular workouts. 

Over time, not using muscles can lead to muscle loss. The good news: muscle loss from reduced activity usually takes weeks to months to develop — and tirzepatide side effects tend to improve as your body adjusts to the medication.

Reduced protein intake

Tirzepatide decreases appetite, which can make it easy to eat much less overall — including less protein. When protein intake drops during weight loss, your body may reduce muscle protein synthesis and break down some lean tissue to meet its energy needs.

Eating enough protein each day can help support muscle preservation during weight loss.

Research is too limited to say for sure if semaglutide (Wegovy, Ozempic) or tirzepatide causes more muscle loss. There have been no studies directly comparing their effects on muscle mass when administered simultaneously or at equivalent doses.

Tirzepatide tends to cause more overall weight loss than semaglutide. Since some lean mass is lost during any significant weight loss, greater total weight loss can mean greater absolute muscle loss. But that doesn’t mean tirzepatide is uniquely harmful to muscle — it likely reflects the larger drop on the scale.

With both medications, about 75–85% of weight lost is fat, and about 15–25% is lean mass. In other words, most of the weight loss comes from fat. Some research also suggests tirzepatide may reduce fat stored inside muscle, which could improve muscle quality.

Based on current evidence, both medications appear to affect muscle in proportion to the amount of weight lost — not because one directly damages muscle more than the other.

Want to maintain muscle mass on tirzepatide? Strategies include eating plenty of protein, adding strength training to your workouts, and getting enough sleep.

1. Optimize protein intake

Getting enough protein is always important, but especially when you’re trying to lose weight. Protein helps you feel fuller after a meal, promotes fat loss, and helps preserve muscle mass. 

Protein is found in animal sources like meat, eggs, and dairy, as well as plant-based sources such as soy, seeds, and lentils. A protein calculator can help you figure out how many grams of protein may be appropriate to target based on your individual goals — whether that’s weight loss, muscle preservation, or building muscle.

2. Do more strength training

Exercise is a helpful, healthy part of any weight management journey. Resistance training in particular has been shown to help prevent muscle loss during weight loss. 

By adding strength training with free weights, resistance bands, or body-weight exercises to your workouts, you can set yourself up to preserve muscle mass while losing weight on tirzepatide.

3. Get enough sleep

Sleep might not sound like a muscle-building activity, but adequate rest is key to healthy body composition.  

Getting 7–8 hours of sleep per night has been shown to help prevent muscle loss and promote fat loss. Research is also clear that even one night of poor sleep can undermine the body’s ability to repair and build muscle.

4. Maintain adequate calorie intake 

Muscles need nourishment. Extreme calorie restriction can lead to greater muscle loss, which is why a slower, steadier approach to weight loss may help protect lean muscle mass. 

Daily calorie needs vary from person to person. A calorie deficit calculator can help estimate how many calories may support weight loss while meeting nutritional needs. Prioritizing protein within that calorie range can also help protect lean muscle mass. 

5. Incorporate daily movement

Strength training is important, but so is regular physical activity. One research review found that both resistance training and endurance exercises — such as running, biking, or brisk walking — are important for preserving muscle during weight loss.

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Does tirzepatide cause muscle loss? Yes, tirzepatide can lead to some muscle loss — but that’s not the full picture. Let’s recap:

• Weight loss from tirzepatide (or any other method) can cause muscle loss. Significant weight loss reduces fat and lean body mass, which includes muscle mass.

• Quality is as important as quantity. In some studies, tirzepatide has also been linked to improvements in muscle quality, such as reduced fat stored within muscle tissue. 

• Proportions matter. Because fat loss is often greater than lean mass loss, some people taking tirzepatide may end up with a higher percentage of their body weight coming from muscle after treatment. 

• Semaglutide vs. tirzepatide muscle loss isn’t fully understood. No studies have directly compared muscle loss from semaglutide versus tirzepatide.

• Muscle loss can be prevented.  Muscle mass can be preserved or even built with strength training, a protein-rich diet, and other lifestyle strategies.

• Muscle loss from tirzepatide isn’t always caused by the medication itself. Muscle loss from tirzepatide isn't always caused by the medication itself. Quitting your workout routine, eating too little protein, or losing weight very quickly can all contribute to muscle decline.