A new real-world analysis suggests that while tirzepatide leads to more significant weight loss than semaglutide, it may also result in greater lean body mass loss.
The study, conducted by nference and posted to medRxiv, analyzed body composition in approximately 8,000 patients. Those treated with tirzepatide lost an average of 1.1% more lean body mass at three months and 2% more at twelve months compared to patients on semaglutide.
This difference was particularly notable among individuals who lost over 20% of their body weight. Around 10% of tirzepatide patients experienced a lean mass reduction exceeding 5%, versus fewer than 7% of semaglutide patients achieving similar overall weight loss.
"Patients shouldn't simplistically be thinking, 'I want to lose X amount of weight and I'll go with the option that delivers greater weight loss,'" stated Venky Soundararajan, Founder and CEO of nference.
Lean body mass, essential for metabolic health, physical function, and healthy aging, can be compromised by significant loss, raising concerns about sarcopenia and frailty, especially in older patients.
Exercise emerged as a critical factor, with reduced exercise tolerance more strongly associated with lean mass decline in tirzepatide patients. Higher doses, longer treatment, and pre-existing musculoskeletal conditions amplified this risk for both therapies. "If you're not exercising when you're on these medicines, you are essentially causing attrition of lean body mass," Soundararajan added.
While tirzepatide is a dual GLP-1/GIP receptor agonist and semaglutide targets GLP-1 alone, the study does not provide a biological explanation for the observed lean mass difference, necessitating further research.