What is Retatrutide? Exploring The New Multi-Action Weight Loss Treatment In Development

With the growing popularity of injectable weight loss treatments, it can be difficult to keep up with all of the new medications available on the market and how they differ from each other. In this blog post, we dive deeper into a new medication in development called retatrutide and unpack its potential as an obesity treatment.

Article Summary:

• Retatrutide is a triple-action weekly injectable weight loss treatment currently being developed by Eli Lilly.
• Unlike current medications like semaglutide and tirzepatide, retatrutide is being developed to activate three gut-hormone receptors (GIP, GLP-1 and glucagon), to offer a multi-action approach to appetite regulation, blood sugar control and fat metabolism.
• Early clinical trials show promising results, including substantial weight loss, improved metabolic health and reduced liver fat.
• Although not yet approved in the UK or elsewhere, it’s currently in Phase 3 trials and may become available as early as 2027.
• This article explores how retatrutide works, its potential benefits, side effects and what to expect as development continues.

What is retatrutide?

Retatrutide is a weekly injectable weight loss medication currently being developed by Eli Lilly (the same company that makes Mounjaro) for the treatment of type 2 diabetes and obesity. [1] As it’s still in development, retatrutide hasn’t been assigned a brand name yet, so in this article, when we refer to retatrutide, we’re referring to both the active ingredient and the name of the medication.

How does retatrutide work?

Retatrutide is being developed to work similarly to other well-known weight loss medications like Wegovy (semaglutide) and Mounjaro (tirzepatide) because it mimics naturally occurring gut hormones.

To quickly refresh, semaglutide (the active ingredient in Wegovy) is a GLP-1 receptor agonist that mimics GLP-1, a hormone that helps regulate appetite and blood sugar. [2] Tirzepatide, the active ingredient in Mounjaro, is a dual GIP/GLP-1 receptor agonist that mimics two hormones: GLP-1 and GIP, giving it a combined effect on appetite, blood sugar control and fat metabolism. [3]

What sets retatrutide apart from these medications is that it’s a GIP–GLP-1–GCG receptor agonist, sometimes referred to as “triple G” or a triple agonist. This means that it mimics three separate hormones, GIP, GLP-1 and glucagon. [4] This triple-action approach is designed to offer more benefits than single-receptor therapies (like semaglutide) or dual-receptor therapies (like tirzepatide).

Here’s what each hormone does:

• GLP-1 (glucagon-like peptide-1) helps your body make more insulin when your blood sugar is high, slows down digestion so food stays in your stomach longer, and works on the brain to make you feel less hungry. [4]
• GIP (gastric inhibitory polypeptide) helps the body make more insulin after meals and may also have helpful effects on how the body handles fat. [4]
• Glucagon helps the body burn more energy by breaking down fat and making sugar in the liver, which can help the body use fat for energy. [4]

Clinical benefits of Retatrutide

Weight Loss

Retatrutide has shown significant and sustained weight loss in clinical trials. Participants in the clinical trials lost up to 24% of their body weight in 48 weeks. Retatrutide does this by targeting multiple gut hormones to reduce appetite and increase feelings of fullness. [4]

Type 2 Diabetes

Trials are indicating the treatment may improve blood sugar control to help manage type 2 diabetes in people with obesity. This is because it helps the body make more insulin and lowers the amount of sugar made by the liver, helping to better control blood sugar.

Liver Disease

Retatrutide is designed to reduce liver fat content which would help treat fatty liver disease (NAFLD/NASH). This would support the liver process and store fat more efficiently while reducing inflammation associated with fatty liver disease. [4]

Heart Health

Trials are also indicating that Retatrutide is helping to lower blood pressure, improve cholesterol profiles, and reduce markers of cardiovascular risk. These benefits come from weight loss, improved blood sugar control, and direct effects on metabolism and blood vessels. [4]

Availability of retatrutide

While the research that’s emerging about retatrutide is remarkable, it’s important to note that it is currently not approved for use in the UK or anywhere else. This is because it still needs to undergo thorough testing to ensure its safety and effectiveness. The good news is that it is in the later stages of clinical trials (currently in phase 3), which means retatrutide may be available to buy with a prescription as early as 2027. [5]

Importantly, this means that if you see any providers claiming to sell retatrutide, you should not use it.

There are warnings from regulatory bodies against the use of unapproved and counterfeit retatrutide products. This is because using unauthorised medications can be unsafe due to unknown quality, dosing and risks.

Cost of Retatrutide

We won’t know how much retatrutide will cost until it is approved for use and becomes available to the public.

Potential Side Effects and Considerations

Like other GLP-1s, the most commonly observed side effects were digestive, including nausea, diarrhoea, vomiting, and constipation.

Some people who took retatrutide in the trials (about 7%) reported unusual skin sensitivity or more sensitive skin, but these symptoms weren’t severe enough to discontinue treatment. [4]

Again, similarly to other GLP-1 medications, these side effects occurred more frequently at higher doses or during dose escalation. However, changing the doses in Phase 3 studies might help reduce side effects of retatrutide before it becomes available. [1]

Dosage and Administration Guidelines

Retatrutide is administered just under the skin, similarly to other injectable weight loss medications, like Wegovy and Mounjaro. In Phase 2 clinical trials, patients were given weekly doses of retatrutide at 1 mg, 4 mg, 8 mg, or 12 mg strengths. However, as trials are still underway, there is currently no approved dose of retatrutide. [1]

Ready to Start Your Weight Loss Journey?

At MedExpress, we’ll help determine which medication is best suited to your needs, based on your medical history and weight loss goals. Learn more about your options here.

*This information is provided for educational purposes only; Retatrutide is not available for prescribing.

References:

1. Drugscom. Retatrutide: What is it and is it FDA approved? [Internet]. Drugs.com. Drugs.com; 2024. Available from: https://www.drugs.com/history/retatrutide.html
2. Wilding JPH, Batterham RL, Calanna S. Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine [Internet]. 2021 Feb 10;384(11):989–1002. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
3. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine [Internet]. 2022 Jun 4;387(3):205–16. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
4. Jastreboff AM, Kaplan LM, Frias JP, Wu Q, Du Y, Sirel Gurbuz, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. The New England Journal Of Medicine [Internet]. 2023 Jun 26;389(6). Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
5. GLP-1 Pipeline Update: November 2024 - Prime Therapeutics - Portal [Internet]. Prime Therapeutics. 2024. Available from: https://www.primetherapeutics.com/glp-1-pipeline-update-november-2024