How does retatrutide compare to tirzepatide?
Retatrutide is an investigational triple hormone agonist (GLP-1, GIP, glucagon) showing promising early results for obesity and type 2 diabetes, while tirzepatide is an FDA-approved dual agonist (GLP-1, GIP) available for use today. The key differences are that retatrutide targets an additional hormone and is still in clinical trials, while tirzepatide is approved and on pharmacy shelves now.
What is Retatrutide?
Retatrutide is not yet FDA-approved and remains an investigational drug developed by Eli Lilly. It is currently in Phase 2 and 3 trials for obesity and type 2 diabetes. Early data from clinical trials show retatrutide produces very high levels of weight loss, averaging 17–24% over 24 to 48 weeks. This exceeds results seen with current FDA-approved drugs.
Studies have so far shown that the proportion of lean mass loss relative to total weight loss with retatrutide was similar to older GLP-1 medications. If trial results continue to be positive, retatrutide may reach approval as early as mid-2026 or early 2027.
What is Tirzepatide?
Tirzepatide is a dual agonist of GLP-1 and GIP, and is FDA-approved for treating type 2 diabetes (brand name: Mounjaro) and obesity (brand name: Zepbound). Similar to retatrutide, tirzepatide is made by Eli Lilly. But tirzepatide is available in pharmacies now, covered by many insurance plans, and widely prescribed for weight management and metabolic health.
Tirzepatide’s dual receptor action delivers powerful appetite suppression and blood sugar control, supported by substantial clinical evidence. Mounjaro was FDA approved in 2022, and Zepbound was approved in 2023 for weight loss and again in 2024 for obstructive sleep apnea.
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How Do They Compare in Weight Loss?
Both medications are highly effective for weight loss, but retatrutide’s early trial results suggest it may have a slight edge: retatrutide has shown 24.2% weight loss at 48 weeks in trials, while tirzepatide has reached up to 21% at 72 weeks. However, retatrutide and tirzepatide have not yet been directly compared in head-to-head trials, and retatrutide’s data remains investigational and limited to smaller studies. Tirzepatide’s efficacy and safety have been confirmed in large, published Phase 3 studies and real-world use.
Safety and Side Effects
Tirzepatide’s safety profile is well-established, with typical side effects including mild-to-moderate nausea, diarrhea, and constipation. Retatrutide appears to have similar gastrointestinal side effects in early studies, which may also include transient nausea and diarrhea. Retatrutide’s long-term safety is unknown until ongoing studies are completed, and more data on rare or severe adverse events is needed.
Availability of Retatrutide and Tirzepatide
Tirzepatide is FDA-approved and available now by prescription from health providers. It can be safely purchased at licensed pharmacies. Retatrutide is currently only available through clinical trials and cannot be safely purchased online or from any supplier.
Bottom Line
Tirzepatide is a proven, FDA-approved option for weight loss and diabetes care available now. Retatrutide offers highly promising trial results for weight loss, but is still experimental and not available outside clinical research settings. Only medications approved by the FDA and prescribed by a qualified provider should be used for obesity or diabetes management.
References
- Abdrabou Abouelmagd, A., Abdelrehim, A. M., Bashir, M. N., Abdelsalam, F., Marey, A., Tanas, Y., Abuklish, D. M., & Belal, M. M. (2025). Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials. Proceedings (Baylor University. Medical Center), 38(3), 291–303. https://doi.org/10.1080/08998280.2025.2456441
- Coskun, T., Wu, Q., Schloot, N. C., Haupt, A., Milicevic, Z., Khouli, C., & Harris, C. (2025). Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial. The lancet. Diabetes & endocrinology, 13(8), 674–684. https://doi.org/10.1016/S2213-8587(25)00092-0
- Eli Lilly and Company. (2025). Clinical Trial Registry. Retrieved from https://trials.lilly.com/en-US/
- Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., Stefanski, A., & SURMOUNT-1 Investigators (2022). Tirzepatide Once Weekly for the Treatment of Obesity. The New England journal of medicine, 387(3), 205–216. https://doi.org/10.1056/NEJMoa2206038
- Jastreboff, A. M., Kaplan, L. M., Frías, J. P., Wu, Q., Du, Y., Gurbuz, S., Coskun, T., Haupt, A., Milicevic, Z., Hartman, M. L., & Retatrutide Phase 2 Obesity Trial Investigators (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. The New England journal of medicine, 389(6), 514–526. https://doi.org/10.1056/NEJMoa2301972
- Mounjaro [package insert]. Updated June 2025. Eli Lilly and Company. Accessed on September 17, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0
- Zepbound [package insert]. Updated July 2025. Eli Lilly and Company. Accessed on September 17, 2025 at https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b
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