Retatrutide Dosing: What We Know So Far About How It’s Used

You may have heard of a new injectable weight loss medication called retatrutide. While this treatment isn’t yet approved for use, here’s what we know about its dosing schedule so far and what it means for patients.

Article Summary:

• Retatrutide is a once-weekly injectable "triple agonist" (GIP, GLP-1, and glucagon) that is currently being developed by Eli Lilly, designed for weight loss and type 2 diabetes management.
• Although retatrutide is still in clinical development, early trial results have shown encouraging findings. Participants lost an average of 24% body weight in 48 weeks, along with improved blood sugar, liver fat reduction and better heart health markers.
• Dosing is still under study, with Phase 2 trials testing 1-12 mg weekly. Side effects are mainly digestive, similar to other GLP-1-based drugs.
• With clinical trials still underway, there is currently no approved dose of retatrutide or any official dosage guides.

What is retatrutide?

Retatrutide is a once-weekly injectable weight loss medication currently being developed by Eli Lilly and Company (the same company that makes Mounjaro) for the treatment of type 2 diabetes and obesity. [1]

It is not available to buy in the UK or online. Retatrutide has not been approved by any regulatory agency anywhere in the world, and it is still going through clinical trials. So, if you see it being sold online, particularly under the name “research peptides,” it is likely to be an unregulated and potentially unsafe product.

“Retatrutide isn’t approved anywhere in the world yet, so it can’t be bought legally in the UK or online. Products currently advertised under this name, especially “research peptides,” are unregulated and could pose a safety risk.”

— Dr Sophie Dix, Head of Medical Affairs at MedExpress

Retatrutide belongs to a class of medications called GIP–GLP-1–GCG receptor agonists, sometimes referred to as “triple G” or a triple agonist. This means that it mimics three separate hormones, GIP, GLP-1 and glucagon. [2] This triple-action approach is designed to offer more benefits than GLP-1 therapies (like semaglutide and liraglutide) or GIP/GLP-1 therapies (like tirzepatide).

How does each hormone help promote weight loss?

• 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. [2]
• GIP (gastric inhibitory polypeptide) helps the body make more insulin after meals and may also have helpful effects on how the body handles fat. [2]
• 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. [2]

What do retatrutide studies suggest about potential benefits?

While much of the reporting around retatrutide focuses on the weight loss results it has produced, studies also demonstrate that it impacts other factors like blood sugar, liver fat, cholesterol, and blood pressure.

Key benefits shown in retatrutide studies:

• Promoted significant weight loss, with participants losing 24% of their body weight on average in 48 weeks. [2] This is more effective than other treatments, including Mounjaro and Wegovy.
• Improves blood sugar control and can help manage type 2 diabetes. [3]
• Reduces liver fat content, making it a promising treatment for fatty liver disease (MASLD/MASH). [4]
• Lowers blood pressure, improves cholesterol profiles, and reduces markers of cardiovascular risk. [2]

How is retatrutide administered in studies?

In clinical trials, retatrutide is injected just under the skin once every week, similarly to other GLP-1 medications like Wegovy and Mounjaro.

Retatrutide dosing in clinical trials

With clinical trials still underway, there is currently no approved dose of retatrutide or any official dosage guides. Here’s what we know about the dosing schedule so far:

In Phase 2 clinical trials, patients were randomly assigned weekly doses of retatrutide as follows: [1]

• 1mg dose
• Initial dose of 2mg and increasing to 4mg
• 4mg dose
• Initial dose 2mg increasing to 8mg
• Initial dose 4mg increasing to 8mg
• Initial dose 2mg increasing to 12mg

[Dosing outside trials is unsafe and not recommended].

In ongoing Phase 3 trials, researchers may adjust the dosing schedule to help reduce retatrutide’s side effects before it becomes available. [1]

Maintenance dose

With other GLP-1 medications like Mounjaro and Wegovy, your maintenance dose refers to the dose that provides the best results, while keeping side effects manageable. This may be the maximum recommended dose for your treatment, or a lower dose that achieves the best balance between effectiveness and minimal side effects.

It is not yet known whether retatrutide will follow a similar dosing schedule, or what an eventual maintenance dose might be, as this will depend on outcomes of ongoing trials and regulatory assessment.

Side effects observed in studies

Like other GLP-1s, the most commonly observed side effects in patients taking retatrutide were digestive, including nausea, diarrhoea, vomiting, and constipation. These side effects occurred more frequently at higher doses or when the strength of the dose was increased. [2]

We don’t have detailed information yet about rare or serious side effects of retatrutide; this information will only be available once larger, long-term trials are complete.

Ready to start your weight loss journey?

If you are starting on your weight loss journey and exploring your options, you can learn more about what treatments are available on MedExpress.

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. 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
3. Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T. 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. 2023 Aug 12;402(10401):529-544. doi: 10.1016/S0140-6736(23)01053-X.???
4. Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, Hartman ML. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat Med. 2024 Jul;30(7):2037-2048. doi: 10.1038/s41591-024-03018-2. Epub 2024 Jun 10.