What is retatrutide? About the experimental weight loss drug

Reviewed by Felix Gussone, MD, Ro, 

Written by Amelia Willson 

Reviewed by Felix Gussone, MD, Ro, 

Written by Amelia Willson 

last updated: Jul 10, 2023

4 min read

Medications like Ozempic, Wegovy, and Mounjaro have become well-known for their impressive weight loss effects. 

But, it appears a new drug called retatrutide may be even more powerful. The experimental drug is currently in clinical trials and not on the market yet, but has lead to an average weight loss as high as 24% after 48 weeks on the highest dosage (12 mg weekly) in people with overweight or obesity.

So, how does retatrutide work, and when can you get your hands on it? Read on.

Ozempic Important Safety Information: Read more about serious warnings and safety info.

Wegovy Important Safety Information: Read more about serious warnings and safety info.

Mounjaro Important Safety Information: Read more about serious warnings and safety info.

What is retatrutide? 

Retatrutide is a new weight loss drug by Eli Lilly, the makers of Mounjaro, a diabetes drug that can lead to significant weight loss. Retatrutide is injected subcutaneously (under the skin) once a week, just like Ozempic, Mounjaro, and other weight loss medications like Wegovy. Retatrutide is currently being tested for treating obesity, type 2 diabetes, or both. Thus far, the results are promising.

In one study, retatrutide was tested in people with type 2 diabetes and a BMI between 25 and 50. The drug produced dose-dependent weight loss, meaning that people lost more weight with higher doses. At 36 weeks, participants taking the lowest 0.5 mg weekly dose lost a little over 3% of their body weight after 9 months (slightly more than the placebo), while those taking the highest 12 mg weekly dose lost nearly 17% of their body weight. The drug also effectively lowered their blood sugar levels.

In another study, retatrutide was tested among people with obesity (BMI of 30 or higher) or with a BMI of 27 or higher and a weight-related condition, such as high cholesterol. At just 24 weeks, participants had lost significant body weight, ranging from a reduction of 7.2% for those taking the lowest 1 mg dose to 17.5% for those taking the highest 12 mg dose. Six months later, at 48 weeks, they had lost even more weight on average— suggesting that with more time on retatrutide, people could continue to lose weight. On average, people taking the highest dose lost just over 24% of their body weight, while those taking the lowest weekly dose (1 mg) lost nearly 9%. 

In both studies, the side effects were mild to moderate, and mostly gastrointestinal—affecting the stomach and intestines—which is similar to other weight loss drugs like Ozempic and Wegovy. The most common side effects included nausea, diarrhea, vomiting, and constipation. Heart rate increases were reported in clinical trials, particularly with higher doses of retatrutide, but declined after the first six months of treatment. The drug was considered safe in both studies, consistent with similar weight loss drugs.

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How does retatrutide compare to other weight-loss drugs? 

Weight loss drugs like Ozempic and Wegovy belong to a drug class known as glucagon-like peptide-1 (GLP-1) receptor agonists. They work by mimicking a gut hormone called GLP-1, which helps to encourage insulin release while also sending fullness signals to your brain to tell you that you’re full. The drugs also delay gastric emptying, slowing the process in which food moves from your stomach into the small intestine. Together, these effects help to lower blood sugar — good for people with type 2 diabetes — and lead to weight loss — good for people looking to lose weight, with or without type 2 diabetes. 

Mounjaro (tirzepatide), another medication by Eli Lilly, is unique among the GLP-1 drug family because in addition to activating the GLP-1 receptor, it also targets glucose-dependent insulinotropic polypeptide (GIP), another hormone involved in insulin release. By working together, Mounjaro has a synergistic effect that leads to even more weight loss and improved blood sugar control. Indeed, people taking the highest dose of Mounjaro lose nearly 21% of their body weight, on average, within a year and a half. By comparison, people taking the highest dose of Wegovy (semaglutide) lose around 15% of their body weight in the same time frame.

“GLP-1 receptor agonists and GIP receptor agonists work on the body in very similar ways,” shared Dr. Sergio Alvarez, MD, a Miami, FL-based board-certified plastic surgeon and CEO of Mia Aesthetics. 

Retatrutide is different in that in addition to GLP-1 and GIP receptors, it also works on the glucagon receptor. “Glucagon tells the liver to release sugar stored in the body. Since sugar is largely stored as fat, the body in turn breaks this fat down, resulting in weight loss”, Dr. Alvarez explains. 

This three-pronged activation may contribute to the superior weight loss effects of retatrutide in comparison to other GLP-1 drugs, as clinical trials have shown so far. As we mentioned earlier, in one of the studies, people taking the highest dose of retatrutide lost about 24% of their body weight in 48 weeks. So, they lost more weight than someone taking Mounjaro and did so in about two-thirds the time.

Retatrutide side effects

Retatrutide shares similar side effects with other GLP-1s — nausea, diarrhea, vomiting, and constipation. According to one study, the side effects were generally mild-to-moderate and occurred when the dose was increased—similar to Ozempic and Wegovy, where side effects also tend to get worse when the healthcare provider increases the dose.  

Dr. Jonathan Kaplan, MD, a board-certified plastic surgeon with Pacific Heights Plastic Surgery in San Francisco, CA, says it is important to find the right dosing for the new drug, once it becomes widely available “That is partially what these early trials are for - to determine the correct sliding scale dosage schedule to minimize side effects while patients are ramping up to the maximum dose.” 

One study of retatrutide found that the drug’s side effects could be somewhat reduced by using a lower starting dose.

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Who may be eligible for retatrutide? 

In phase 2 trials, retatrutide significantly reduced hemoglobin A1C levels in people with type 2 diabetes over a six-month period, while people with obesity or overweight lost about 24% of their body weight within a year. “If these results can be replicated, it’s quite likely that retatrutide will be granted FDA approval for both weight loss and type 2 diabetes,” shared Dr. Alvarez, while cautioning that we’ll have to wait for the results of the phase 3 trials to know for sure.

Eli Lilly is currently enrolling participants for phase 3 trials of retatrutide, which are expected to last until 2025. If those trials go well, “it’s likely that retatrutide will be available to people with type 2 diabetes as well as obese people with a BMI of 30 or above or a BMI of 27 who already have weight-related health issues,” Dr. Alvarez shared. “These eligibility guidelines would align with the current guidelines used by similar medications.”

“The FDA approval process is sometimes unpredictable as the agency can ask for more information about a drug before granting approval,” shared Dr. Alvarez. “Clearly, this delays the process. At the moment, I would guess that retatrutide could go to market late in 2026 or early in 2027. This is only an educated guess, however.”

DISCLAIMER

If you have any medical questions or concerns, please talk to your healthcare provider. The articles on Health Guide are underpinned by peer-reviewed research and information drawn from medical societies and governmental agencies. However, they are not a substitute for professional medical advice, diagnosis, or treatment.

  • Alvarez, S. (2023, June 30). Personal communication [email].

  • Collins, L. & Costello, R. A. (2023). Glucagon-like Peptide-1 Receptor Agonists. StatPearls. Retrieved Jul. 3, 2023 from https://www.ncbi.nlm.nih.gov/books/NBK551568/

  • Eli Lilly. (2023). A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease (TRIUMPH-3). Lilly Trials. Retrieved Jun. 28, 2023 from https://trials.lilly.com/en-US/trial/405675

  • Holst, J. J. & Rosenkilde, M. M. (2020). GIP as a therapeutic target in diabetes and obesity: insight from incretin co-agonists. The Journal of Clinical Endocrinology & Metabolism, 105, 8, 2710–2716. doi:10.1210/clinem/dgaa327. Retrieved from https://academic.oup.com/jcem/article/105/8/e2710/5847843

  • Jastreboff-a, A. M., Kaplan, L. M., Frías, J. P., et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. The New England Journal of Medicine, 10.1056/NEJMoa2301972. Advance online publication. doi:10.1056/NEJMoa2301972. Retrieved from https://pubmed.ncbi.nlm.nih.gov/37366315/

  • Jastreboff-b, A. M., Aronne, L. J., Ahmad, N. N., et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. The New England Journal of Medicine, 387(3), 205–216. doi:10.1056/NEJMoa2206038. https://www.nejm.org/doi/10.1056/NEJMoa2206038

  • Kaplan, J. (2023, June 30). Personal communication [email].

  • Nason, S. R., Antipenko, J., Presedo, N., et al. (2021). Glucagon receptor signaling regulates weight loss via central KLB receptor complexes. JCI Insight, 6(4), e141323. doi:10.1172/jci.insight.141323. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934938/

  • Rosenstock, J., Frias, J., Jastreboff, A. M., et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA. Lancet (London, England), S0140-6736(23), 01053-X. Advance online publication. doi:10.1016/S0140-6736(23)01053-X. Retrieved from https://pubmed.ncbi.nlm.nih.gov/37385280/

  • Urva, S., Coskun, T., Loh, M. T., et al. (2022). LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Lancet (London, England), 400(10366), 1869–1881. doi:10.1016/S0140-6736(22)02033-5. Retrieved from https://pubmed.ncbi.nlm.nih.gov/36354040/

  • Wilding, J. P. H., Batterham, R. L., Calanna, S., et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine, 384(11), 989–1002. https://doi.org/10.1056/NEJMoa2032183. Retrieved from https://www.nejm.org/doi/10.1056/NEJMoa2032183


How we reviewed this article

Every article on Health Guide goes through rigorous fact-checking by our team of medical reviewers. Our reviewers are trained medical professionals who ensure each article contains the most up-to-date information, and that medical details have been correctly interpreted by the writer.

Current version

July 10, 2023

Written by

Amelia Willson

Fact checked by

Felix Gussone, MD


About the medical reviewer

Felix Gussone is a physician, health journalist and a Manager, Medical Content & Education at Ro.

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