Retatrutide versus Tirzepatide: What is the Difference in Muscle Retention

⚠️ Important: This article is not advice. Retatrutide is a drug that is still being tested and has not been approved by the FDA. If you have health concerns you should talk to a doctor.

Reviewed by: Alex M. Rivera, B.S. Molecular Biology

The Trade-Off in Body Composition

Retatrutide and Tirzepatide are two drugs that help with weight loss. They are part of a class of medicines that use hormones to help people lose weight. Both drugs help people lose a lot of weight. Up to 24% with Retatrutide and 15-21% with Tirzepatide.. A big question is, how much of the weight lost is fat and how much is muscle?

The short answer is that Tirzepatide helps keep muscle than Retatrutide. 75% Of the weight lost with Tirzepatide is fat while about 62-67% of the weight lost with Retatrutide is fat. This means that Retatrutide causes muscle loss than Tirzepatide.

This difference happens because the two drugs work in ways. Tirzepatide helps the body use insulin better and reduces hunger. Retatrutide does the thing but it also increases the amount of energy the body uses which can cause more muscle loss.

1. How These Drugs Affect Muscle Differently

Tirzepatide is a drug that helps the body use insulin better and reduces hunger. It does this by activating two hormones in the body. This helps people lose weight because it reduces hunger and helps the body use insulin better. Tirzepatide does not increase the amount of energy the body uses so it does not cause much muscle loss.

Retatrutide is a drug that does the thing as Tirzepatide but it also increases the amount of energy the body uses. This causes weight loss but it also causes more muscle loss. The increase in energy use is what causes the muscle loss.

The trade-off is clear: more energy use means weight loss but it also means more muscle loss.

2. Tirzepatide: The SURMOUNT-1 Study

The SURMOUNT-1 study looked at how Tirzepatide affects body composition. The study found that 75% of the weight lost with Tirzepatide is fat and only 25% is muscle. This is a thing because it means that people who take Tirzepatide will lose more fat and less muscle.

The study also found that Tirzepatide helps improve muscle quality. It reduces the amount of fat inside the muscles, which makes them stronger and more efficient.

3. Retatrutide: The Phase 2 Study

The Phase 2 study looked at how Retatrutide affects body composition. The study found that Retatrutide causes muscle loss than Tirzepatide. 33-38% Of the weight lost with Retatrutide is muscle compared to 25% with Tirzepatide.

The study also found that Retatrutide causes fat loss than Tirzepatide but it also causes more muscle loss. This is because Retatrutide increases the amount of energy the body uses which can cause muscle loss.

4. Head-to-Head Comparison

Here is a comparison of the two drugs:

| Parameter | Tirzepatide | Retatrutide |

|———–|————|————|

Mechanism | Dual hormone activator | Triple hormone activator |

Weight loss | 15-21% | 24-28% |

Fat loss | 33.9% | 26.1% |

Muscle loss | 10.9% | 6.5 kg |

Muscle loss percentage | 25% | 33-38% |

FDA approval | Approved | Not approved |

5. Real-World Considerations

The increase in energy use caused by Retatrutide can be a problem. It can cause muscle loss if people do not eat protein or exercise enough. Tirzepatide on the hand helps improve muscle quality by reducing the amount of fat inside the muscles.

Exercise is important for both drugs. People who take either drug should exercise regularly. Eat enough protein to prevent muscle loss.

6. Summary, for Researchers

Here are the points:

| Question | Answer |

1. Which drug preserves muscle?
   Tirzepatide
   
2. Why does Retatrutide cause muscle loss?
   It increases energy use, which can cause muscle loss
   
3. Does Tirzepatide harm muscle quality?
   No it improves muscle quality by reducing fat inside the muscles
   
4. Can we stop muscle loss?
   Yes. We need to do resistance exercises and eat a lot of protein at 1.6 grams for every kilogram we weigh every day for both tirzepatide and retatrutide to work well.
   
5. Which medicine is better for who?
   Tirzepatide is better if we want to keep our muscle mass. Retatrutide is better if we want to lose a lot of weight including fat and we are willing to do exercises to save our muscles.

References

1. Look M, Dunn JP, Kushner RF and others. What happens to our body when we take tirzepatide to lose weight as seen in the SURMOUNT-1 study of adults who’re overweight or obese. Diabetes Obes Metab. 2025;27(5):2720-2729. DOI: 10.1111/dom.16275

2. Jastreboff AM, Kaplan LM, Frías JP and others. Using retatrutide a medicine that works on three hormones to treat obesity. A phase 2 trial. N Engl J Med. 2023;389:514-526. DOI: 10.1056/NEJMoa2301972

3. Locatelli JC, Costa JG, Haynes A and others. Can exercise help us lose weight and keep our muscles when we take medicines like tirzepatide and retatrutide? Diabetes Care. 2024;47(10):1718-1730. DOI: 10.2337/dci23-0100

4. Sattar. Others. What happens to our muscles when we take tirzepatide as seen in people with type 2 diabetes: a -hoc analysis from SURPASS-3 MRI. Lancet Diabetes Endocrinol. 2025. DOI: 10.1016/S2213-8587(25)00027-0

5. Frias. Others. How retatrutide affects our body composition in people with type 2 diabetes: a substudy of a phase 2 trial. *Lancet Diabetes Endocrinol*. 2025;13(8):674-684. DOI: 10.1016/S2213-8587(25)00092-0

6. Comparing Retatrutide and Tirzepatide: Lean. Fat Loss. IncreaseMyT. 2026.

7. Retatrutide vs Tirzepatide: How Do They Compare? GoodRx. 2026.

8. Retatrutide vs Tirzepatide: A Comparison of the Triple Agonist. Instalab. 2026.

9. Using Retatrutide to Cut Fat, Not Muscle: Early Data. Voy. 2025.

10. Tirzepatide Linked to Muscle Loss Than Semaglutide. EMJ Reviews. 2026.

This article was. Reviewed by Alex M. Rivera, B.S. Molecular Biology our, in-house science reviewer. Alex M. Rivera only uses information from trusted sources. Updates the content regularly. Remember, this is not advice. Always talk to a doctor.