Does retatrutide (tirzepatide) retain muscle better than Ozempic (semaglutide)?

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Last updated: July 8, 2025View editorial policy

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From the Guidelines

Retatrutide (tirzepatide) may preserve muscle mass better than semaglutide (Ozempic) due to its triple-hormone action, which could lead to more selective fat loss and better preservation of lean muscle mass. This is based on the most recent and highest quality study available, which suggests that tirzepatide's action on glucagon receptors may help maintain metabolic rate and reduce muscle breakdown during weight loss 1. Some key points to consider when using either medication for weight loss and diabetes management include:

  • Maintaining adequate protein intake (1.6-2.0g/kg of body weight daily) to support muscle mass
  • Engaging in regular resistance training 2-3 times weekly to build and maintain muscle
  • Ensuring sufficient caloric intake to minimize muscle catabolism
  • Monitoring for potential side effects and adjusting treatment as needed It's also important to note that while tirzepatide may have a muscle-sparing effect, definitive comparative data with semaglutide is limited, and more research is needed to fully understand the effects of these medications on muscle mass 1. In clinical trials, tirzepatide has shown approximately 15-20% total body weight reduction with about 70-75% of that coming from fat tissue, suggesting better muscle preservation compared to semaglutide 1. Overall, the choice between retatrutide (tirzepatide) and semaglutide (Ozempic) should be based on individual patient needs and medical history, and patients should work closely with their healthcare provider to determine the best course of treatment.

From the Research

Comparison of Retatrutide and Ozempic

  • Retatrutide (tirzepatide) and Ozempic (semaglutide) are both used for the treatment of obesity and type 2 diabetes.
  • Studies have shown that retatrutide stimulates Glucagon-like peptide 1 (GLP-1), Glucose-dependent insulinotropic polypeptide (GIP) receptors, and glucagon receptors, which may contribute to its effectiveness in weight loss and glucose control 2, 3.
  • In terms of muscle retention, there is limited direct comparison between retatrutide and Ozempic.
  • However, a study on retatrutide's effects on human atrial preparations found that it increased force of contraction in a concentration- and time-dependent manner, suggesting potential positive effects on muscle function 4.
  • Another study found that retatrutide resulted in substantial reductions in body weight, with a mean percentage change in body weight of -17.5% at 24 weeks, which may be associated with changes in muscle mass 5.
  • In comparison, Ozempic (semaglutide) has been shown to result in significant weight loss, but its effects on muscle retention are not as well-studied.
  • A study comparing retatrutide to dulaglutide, another GLP-1 receptor agonist, found that retatrutide resulted in greater reductions in body weight, but the comparison to Ozempic (semaglutide) is still needed 6, 3.
  • Overall, while there is some evidence to suggest that retatrutide may have positive effects on muscle function and retention, more research is needed to directly compare its effects to those of Ozempic (semaglutide) 2, 4, 5, 6, 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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