Study Reveals Mounjaro Causes More Lean Body Mass Loss Than Ozempic—Here’s Why It Matters

New research indicates that tirzepatide-based medications, such as Mounjaro, may result in a higher loss of lean body mass compared to semaglutide-based drugs like Ozempic. This finding comes as GLP-1 medications continue to gain popularity for their significant weight-loss benefits.

Key Findings: Tirzepatide vs. Semaglutide

A study published in medRxiv—a preprint server for health sciences—examined 7,965 individuals newly prescribed GLP-1 medications. Of these participants, 6,196 were using semaglutide (e.g., Ozempic, Wegovy), while 1,769 were using tirzepatide (e.g., Mounjaro, Zepbound). Researchers measured lean body mass before and after initiating treatment.

The results showed that tirzepatide users experienced a 2% greater loss of lean body mass by 12 months compared to semaglutide users. In the first three months, the difference was 1.1%.

"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. In other words, the more aggressive the weight loss, the greater the likelihood that some of that loss includes muscle, not just fat."

— Jeffrey Lee, MD, double board-certified plastic surgeon and founder of JL Plastic Surgery

Why Lean Body Mass Loss Matters

Lean body mass includes muscle, connective tissue, and other essential components that support metabolism, strength, and physical function. Excessive loss of lean mass can lead to:

• Fatigue and reduced physical performance
• Increased risk of injury
• Slower metabolism and metabolic complications

Dr. Lee emphasized that while GLP-1 medications are effective for weight loss, they may also accelerate muscle loss if not managed properly.

Who Is at Higher Risk?

The study identified several factors that may increase the risk of lean body mass loss:

• Higher doses and longer treatment duration
• Lower tolerance for exercise during treatment
• Pre-existing musculoskeletal conditions

Additionally, the research noted that approximately 10% of tirzepatide users achieved a 20% weight reduction alongside a 5% reduction in lean body mass—a loss observed in far fewer semaglutide users.

What Can Patients Do?

Experts recommend incorporating strength training and resistance exercises into treatment plans to help preserve muscle mass. Maintaining a balanced diet rich in protein may also mitigate lean mass loss.

Note: This study is a preprint and has not yet undergone peer review.