Mounjaro May Lead to Greater Lean Body Mass Loss than Ozempic. Here’s Why

• A recent study found that semaglutide medications, such as Ozempic, may better preserve lean body mass than tirzepatide medications, such as Mounjaro.
• This may be due in part to tirzepatide leading to more significant weight loss.
• The findings show that maintaining a strength-training routine may help reduce muscle loss when using GLP-1s.

GLP-1 drugs have exploded in popularity due to their ability to promote significant weight loss. This class of medications has helped transform the way healthcare professionals treat obesity.

Semaglutide medications, such as Ozempic or Wegovy, and tirzepatide medications, such as Mounjaro and Zepbound, are the most popular GLP-1 drugs for weight loss.

A study recently published in medRxiv has shown that while tirzepatide appears to lead to greater weight loss, there may be a trade-off of a higher loss of lean body mass than semaglutide.

Lean body mass includes muscle, connective tissue, and other essential components that support metabolism, strength, and overall physical function.

This study is a preprint and has not yet been peer-reviewed in a scientific journal, but here’s what the researchers found.

The researchers measured each participant’s lean body mass before and after beginning their first prescription of either semaglutide or tirzepatide. They found that those on tirzepatide consistently showed a greater loss of lean body mass.

People on tirzepatide lost about 1.1% more lean body mass than those using semaglutide in the first 3 months of using the medications. This increased to 2% more lean body mass loss by 12 months.

“This finding is not entirely surprising. Tirzepatide is generally more potent than semaglutide, and with greater overall weight loss, you often see a higher degree of lean mass loss as well,” said Jeffrey Lee, MD, double board certified plastic surgeon and founder of JL Plastic Surgery, who also prescribes GLP-1s. Lee was not involved in the study.

“In other words, the more aggressive the weight loss, the greater the likelihood that some of that loss includes muscle, not just fat,” Lee told Healthline.

The study emphasizes the importance of physical activity while taking GLP-1s.

Lee agreed. “Exercise (particularly strength training) plays a critical role in preserving lean muscle mass while on GLP-1 medications,” he said.

“I emphasize to my patients that both adequate protein intake and exercise are essential for preserving muscle. Both aerobic exercise and resistance training are highly beneficial,” added Mir Ali, MD, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA. Ali wasn’t involved in the study.

Lee noted that resistance training signals the body to maintain muscle, even in a calorie deficit, and should be a core part of any weight loss plan using GLP-1 drugs.

Ali emphasized that adequate protein intake is also an important factor in supporting muscle preservation.

“Just as important is the pace of weight loss — slower, more gradual weight reduction tends to better preserve lean mass compared to rapid weight loss. This is why careful dose titration and ongoing monitoring are key when using GLP-1s,” Ali told Healthline.