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What is Triple-G (Retatrutide) and how is it different?
‘Weight loss injections are continuing to evolve,’ says Dr Daniel Atkinson, Treated Clinical Lead.
‘First generation GLP-1s were bettered by second generation injections. And the next adaptation is retatrutide, a ‘triple agonist’ which early studies have shown to be even more effective for weight loss.’
Medically reviewed by
Alexandra Cristina Cowell, Writer & Clinical Content Reviewer
- Nicknamed ‘Triple-G’, retatrutide is the first weight loss injection to target three hormone receptors.
- By having a more comprehensive effect on weight management, it could prove to be an even more effective option than the best available treatments currently.
Here, we’ll take a closer look at how Retatrutide works.
How does Retatrutide work?
Retatrutide works by targeting hormones involved in hunger, satiety, and metabolism. It’s the first ‘triple hormone receptor agonist’, and these mechanisms set Retatrutide apart from existing weight loss injections.
Although it’s yet to be released, early trials of retatrutide have shown that this new, innovative technology has helped people lose weight in a shorter amount of time than they have using the previous generation of injections, which include Mounjaro and Wegovy.
Treated Superintendent Pharmacist Sanjeda Chowdury suggested that the effect of Retatrutide on glucagon receptors, the first injection of its kind to work in this way, could make it the most effective weight loss treatment yet.
‘Early studies suggest Retatrutide will help people lose weight in the shortest amount of time,’ says Sanjeda. ‘This is because it offers a unique mechanism we haven’t seen before from other weight loss injections. As well as targeting GLP-1 and GIP receptors, which other treatments like Mounjaro do, Retatrutide also works on glucagon receptors (GCG).’
‘Activating glucagon receptors encourages your body to burn more calories, which can help you reach a calorie deficit faster. Existing weight loss injections focus more on helping you control your appetite while balancing your blood sugar, but they don’t necessarily help you expend significant amounts of energy. Using Retatrutide along with increasing your activity levels, which is the recommended advice when using a weight loss injection, means you’ll be burning even more calories while also consuming fewer.’
Each of the hormones that Retatrutide mimics plays a slightly different role in weight management.
GLP-1
Glucagon-like peptide-1 (GLP-1) is an incretin hormone, a small protein messenger (gut peptides) that helps to regulate your appetite and tell you when you’re full. It stimulates the release of insulin, which lowers your blood sugar. It also acts on your appetite by telling you when you’ve had enough to eat. Retatrutide mimics the action of and activates GLP-1 receptors, reducing your appetite while also slowing down gastric emptying (the rate that food moves through the gut).
GIP
Glucose-dependent insulinotropic polypeptide (GIP) is another type of incretin hormone that is released when you eat. Like GLP-1, GIP acts as a satiety signal to tell you when you’re full. It also increases insulin production, and helps regulate fat metabolism and blood sugar. Activating GIP receptors is thought to enhance the effects of GLP-1 when these two actions are combined.
GCG
The effect of Retatrutide on glucagon (GCG) is what sets it apart from other existing weight loss injections. Glucagon works by counteracting the effects of raised insulin, by raising your blood sugar levels. Activating GCG receptors alone would then work against efforts to lose weight, but when activated alongside GLP-1 and GIP receptors, GCG can increase overall energy expenditure and fat burning without raising blood glucose excessively. This novel combined mechanism means retatrutide is the first weight loss injection to target three metabolic pathways.
How effective is Retatrutide compared to other weight loss injections?
Retratutide has been shown to help people lose weight at a faster rate than the currently available second-generation weight loss injections.
In clinical studies, Wegovy was observed to help people lose 15% of their initial body weight after 68 weeks. Mounjaro trials showed an improvement in this rate of weight loss, showing an average loss of around 22% from starting weight for participants using the highest dose (15mg) pen for 72 weeks.
Retatrutide trials have shown an even faster rate of success than both Wegovy and Mounjaro. After just 48 weeks, participants using the 12mg dose lose an average of 24% of their initial weight.
When will Retatrutide be available in the UK?
Retatrutide is currently in phase 3 clinical trials, which are expected to conclude in 2026.
This means that Eli Lilly, the manufacturer of Retatutide, could make it available in the UK from mid-late 2026, once it’s been approved by the MHRA. But its release date is yet to be confirmed, and it’s fairly common for treatments to be delayed when coming to market.
Amazingly, despite Retatrutide still being in its development stages, unlicensed, illegal versions of it have reportedly already been sold online.
Fake versions of weight loss injections might not always be easy to differentiate from official ones once you have them in your hand. Signs to look out for might be things like flimsy packaging, spelling mistakes or incorrect logos. Weight loss injections always come pre-filled, so if you receive any that ask you to mix a powder with water before injected, it’s highly likely to be an unofficial product.
The easiest way to avoid using counterfeit versions of treatments is to make sure you get them from legitimate sources. For example, weight loss injections should never be sold through social media platforms, and instead need to be prescribed by a licensed clinician.
If you’re getting treatments like Retatrutide online, make sure the website clearly displays its Care Quality Commission (CQC) registration and that clinicians are registered with the General Medical Council (GMC), the General Pharmaceutical Council (GPhC), or the Nursing and Midwifery Council (NMC).
Will Retatrutide be prescription-only?
Given the status of other GLP-1s, Retatrutide will almost certainly be a prescription-only weight loss treatment.
This is because a clinician needs to check your medical history and whether or not you fit the suitable criteria for using weight loss injections. You can normally use weight loss treatments if your BMI is 30 or above, or if it’s 27 or above and you have a weight-related condition like diabetes or heart disease.
Will you be able to switch to Retatrutide when it is available?
As more become available, it’s becoming more common for people to switch weight loss treatments, but you’ll always need to do so under the supervision of your clinician.
If you’re not happy with your current treatment and feel like Retatrutide (once it becomes available) seems like a better option, you can discuss changing medications with them.
There’s no specific guidance currently on what to do when changing weight loss medications. In some cases, if you were on a higher dose of one type of medication, you might be advised to start again from the lowest dose of your new medication. This is usually the case if you’re switching from Wegovy to Mounjaro – you might be advised to leave a gap of at least six weeks between your last dose of Wegovy and your first dose of Mounjaro. And when doing this, you’d start Mounjaro treatment on the 2.5mg lowest dose pen.
But some practices – including Treated – have developed ‘switching policies’ that mean when you go from using Mounjaro to Wegovy, you can start at a slightly higher dose depending on which of Mounjaro you were on, and when your last injection was.
It’s likely, given that there are three active ingredients in Retatrutide (as opposed to two in Mounjaro and one in Wegovy), that if you were already at an elevated dose of Mounjaro or Wegovy, you’d be advised to observe the ‘wait 6 weeks and start at the lowest dose’ rule when switching to Retatrutide – because a clinician would want to make sure Retatrutide, which has a different, more complex mode of action, works for you at a low dose before increasing.
Changing treatments won’t be recommended if the one you’re using is working effectively, either. There are a lot of weight loss options available, and there’s no guarantee changing to a newer medication will help you reach your target faster. But changing might be advised if you’re not satisfied with your current treatment, or if it causes too many unwanted side effects. Whatever your reason is for requesting to switch treatments, your clinician can support you and make sure you know exactly what changing medications will involve.
Will you be able to use Retatrutide long-term?
The length of time you use a weight loss treatment for will come down to your personal weight loss goals. If there’s a target weight you’re trying to reach, this can help you develop a plan for the best way to get there. This will also give you some idea of how long you can expect to use your medication for.
This is something you can discuss with a clinician before starting treatment. When Retatrutide is released, and if it’s a safe and suitable option for you, you can discuss factors like the long-term costs, side effects, and when to stop using your treatment with your weight loss goals in mind.
Weight loss rarely follows a linear path, and each person’s journey is different. The same can be said about using weight loss injections — while there are studies that support their effectiveness, this isn’t a guarantee that the one you choose will work the way you hope it will. People lose weight at different rates, which makes it difficult to say concretely when a person can expect to see their target number on the scales.
The NHS limits subsidised weight loss injection use to two years. There’s currently little research into how using treatments like Retatrude beyond this can impact your health. So it’s difficult to say currently if these injections have a durational maximum.
Usually, once you’ve remained on the maintenance dose of a treatment for a while, you’ll begin to taper off the medications and try to keep the weight you’ve lost off by continuing the lifestyle changes you made during your treatment plan.
Reference Popover #ref1
Treated trusted source
Jastreboff, A. M., Kaplan, L. M., Frias, J. P., et al. (2023).
'Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial', The New England Journal of Medicine, vol. 389.
Reference Popover #ref2
Treated trusted source
Samms, R.J., Coghlan, M.P. and Sloop, K.W. (2020).
How May GIP Enhance the Therapeutic Efficacy of GLP-1? Trends in Endocrinology & Metabolism, 31(6), pp.410–421.
Reference Popover #ref3
Treated trusted source
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, vol. 384, no. 11, pp. 989–1002.
Reference Popover #ref4
Treated trusted source
Weghuber, D., Fruhbeck, G., Tews, D., et al. (2022).
'Once-Weekly Semaglutide in Adolescents with Obesity', The New England Journal of Medicine, vol. 387, no. 24.
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