Retatrutide vs tirzepatide: how do they compare?
Retatrutide is an investigational triple hormone agonist (GLP-1, GIP, glucagon) showing promising 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 and Company. 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 28% over 80 weeks. This exceeds results seen with current FDA-approved drugs. Additionally, studies show a reduction in knee osteoarthritis pain and improvement in sleep apnea.
TRANSCEND-T2D-1 study
In a Phase 3 clinical study of adults with type 2 diabetes, people taking retatrutide saw up to a 2% reduction in their A1C blood tests, and up to 17% weight loss after 40 weeks. This was compared to an A1C reduction of 0.8% and 2.5% weight loss in the placebo group.
TRIUMPH-1 phase 3 study for weight loss
In a Phase 3 clinical study of adults with obesity or overweight and at least one weight-related condition, people taking 12 mg of retatrutide lost an average of about 28% of their body weight over 80 weeks. This is compared to around -2% change in body weight in the placebo group.
In people with knee osteoarthritis, pain scores decreased by nearly 73%. Retatrutide also improved sleep for those with moderate-to-severe obstructive sleep apnea, decreasing breathing pauses by about 61% (an average of 36 fewer events per hour).
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.
Related questions
- Zepbound vs Mounjaro: Comparison Guide for Weight Loss and Diabetes Treatment
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How Do They Compare in Weight Loss?
Both medications are highly effective for weight loss, but retatrutide’s Phase 3 trial results have shown an average of 28.3% weight loss (70.3 lbs) at 80 weeks. Tirzepatide has reached up to 21% at 72 weeks. In one study, adults with type 2 diabetes who took retatrutide 12 mg lost 17% of their body weight after 40 weeks. Retatrutide and tirzepatide have not yet been directly compared for weight loss in head-to-head trials.
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 studies, including transient nausea, diarrhea, and constipation. These side effects happened more frequently when raising the dose.
See Retatrutide Consumer Information.
Availability of Retatrutide and Tirzepatide
Tirzepatide is FDA-approved and available now by prescription from healthcare 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/
- Eli Lilly and Company. (2026, March 19). Lilly's triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes [Press release]. https://lilly.gcs-web.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-demonstrated-significant
- Eli Lilly and Company. (2026, May 21). Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss
- Eli Lilly and Company. (2026, June 6). Lilly's triple agonist, retatrutide, drove substantial improvements in weight, A1C, knee osteoarthritis pain, and obstructive sleep apnea, demonstrating its remarkable potential to treat obesity and its complications [Press release]. https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-drove-substantial-improvements
- 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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