Retatrutide
What is retatrutide?
Retatrutide is the latest weekly injectable weight loss medication that’s currently in phase 3 clinical trials. It contains the active ingredient, retatrutide, and is being developed by the same manufacturer as Mounjaro, Eli Lilly, for the management of obesity and type 2 diabetes [1]. Retatrutide is a triple agonist, targeting the receptors of 3 hormones that can impact appetite, weight, and blood sugar levels. Retatrutide is still undergoing clinical trials to assess its safety and effectiveness. As it’s still in development, retatrutide hasn’t been assigned a brand name yet, but it commonly referred too as Reta or GLP1- 3.
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]
Health 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]
Clinical trial & results
Retatrutide is currently in phase 3 clinical trials for weight loss, but results from phase2 are promising.
At a 4mg weekly dose, participants had an average loss of 17% of their body weight over 48 weeks and:
92% of participants lost at least 5% of their starting body weight
75% lost at least 10% of their body weight
60% lost at least 15% of their starting weight
At the highest weekly 12mg dose, participants lost an average of 24.2% of their starting body weight over 48 weeks. Within this group, 26% of people also lost at least 30% of their initial body weight.
Retatrutide dosage
In phase 2 clinical trials, retatrutide was given in the following doses:
Starting dose: 1mg, 2mg or 4mg
Maintance dose: 1mg, 4mg, 8mg or 12mg per week
Highest dose: 12mg per week
Participants injected once a week and increased their dose every 4 weeks.
However, there is no ‘official’ retatrutide dosage schedule yet because it’s still being researched for its effects on weight loss. Like other weight loss injections, retatrutide was started at a low dose and gradually increased over several weeks, to allow the body to get used to the medication and minimise the chance of side effects.
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
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
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
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
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