Retatrutide (Triple G): What It Is, How It Works, Trial Results, and UK Availability

Key Takeaways

• Retatrutide (Triple G) is a new triple-action weight loss injection that targets GLP-1, GIP and glucagon receptors.

• Early phase 2 trials show up to 24 percent weight loss in 48 weeks, exceeding results seen with Wegovy and Mounjaro.

• Retatrutide also shows early benefits for blood sugar control, liver fat reduction and metabolic health, but long-term data is still needed.

• The most common side effects so far are nausea, vomiting, diarrhoea and constipation, similar to other GLP-1 treatments.

• Retatrutide is not approved in the UK, USA or anywhere else, and cannot be legally purchased. Any online “Triple G” products are unsafe.

• Phase 3 TRIUMPH trials end in 2026, after which regulators will review full safety data before any approval is possible.

• Until then, licensed alternatives like Mounjaro and Wegovy remain the safest proven medical options for weight loss under clinician supervision.

What is retatrutide (Triple G)?

Retatrutide is a novel treatment currently being developed by Eli Lilly for weight loss and management of type 2 diabetes. It will be the first of its kind as a triple therapy treatment, challenging current treatments already available.

As it is still undergoing clinical trials, it is not yet approved for routine prescribing in the UK though ongoing research from clinical studies are promising. The drug is also waiting to be FDA approved in the USA.

How is retatrutide different from other weight loss injections?

Retatrutide is different from other loss injections in that it is the first of its kind to offer triple therapy. Currently licensed treatments available are Wegovy (activates one hormone) and Mounjaro which activates two hormones.

In addition to the GLP-1 and GIP receptors activated by Mounjaro, Retatrutide also activates glucagon receptors which may influence energy use and fat metabolism by helping to use up stored sugar in the liver.

How does Retatrutide work? (GLP-1, GIP and glucagon explained)

GLP-1: appetite and blood glucose regulation

GLP-1 or glucagon like peptide-1 slows stomach emptying and triggers insulin release. Wegovy, a GLP-1 receptor agonist helps suppress appetite and control blood sugars. In doing so, it supports weight loss and improves diabetes management.

GIP: supporting insulin response

Another hormone is glucose dependent insulinotropic polypeptide or GIP. Mounjaro is a dual action therapy which in addition to what Wegovy does, activates GIP receptors.

This helps release insulin after eating which, when combined with GLP-1, can maintain better blood sugar control whilst promoting greater weight loss by improving how the body handles food and energy.

By activating both receptors, Mounjaro has shown to promote a greater reduction in body weight compared to Wegovy.

Glucagon: energy use and fat breakdown

Retatrutide targets the same two receptors Mounjaro does but additionally glucagon receptors. This causes the liver to release stored sugar, temporarily raising blood sugars. At the same time, GLP-1 and GIP stimulate insulin release to stabilise these levels.

Maintaining stable sugar control helps reduce appetite whilst using stored energy. Once liver stores have been used, the body can shift to burning fat as an energy source.

The main difference between Retatrutide vs current treatments is this ability to tap into energy stores in the liver. However, as it is still in early clinical trials, more research is needed to confirm its safety and efficacy in a wider range of patients. This includes different age groups and in patients with other medical conditions such as cardiovascular disease or high blood pressure.

What do clinical trials show so far?

Phase 2 clinical trials, reported in the New England Journal showed significant reductions in weight and improvements in liver fat. This double-blind, placebo-controlled study tested multiple doses of Retatrutide, administered once weekly. Percent change in body weight was then analysed.

At 24 weeks, the mean percentage weight loss was:

• 1mg - 7% change

• 4mg - 13% change

• 8mg - 17.3% change

• 12mg - 17.5% change

• Placebo - 1.6%

At 48 weeks, the mean percentage weight loss was:

• 1mg - 8.7%

• 4mg - 17.1%

• 8mg - 22.8%

• 12mg - 24.2%

• Placebo - 2.1%

These results highlight that increased doses can lead to meaningful weight loss. However, as it is still being studied, further information is needed to confirm its efficacy and safety.

In addition to weight loss results, the Retatrutide clinical trials also showed a marked reduction in liver fat of up to 80% at the higher doses of 8 and 12 mg. Improvement in blood sugar levels were also reported.

Most common side effects were nausea, vomiting, diarrhoea and were dose-dependent. No severe side effects were observed though further Retatrutide trials are required over a longer period to define the full safety profile.

Interpreting the numbers

The trials talk about mean percentage weight reduction - this represents an average weight loss amongst all the participants in the clinical trials. Individual responses can vary based on metabolism, lifestyle choices and how well you adhere to the prescribed treatment.

Whilst they show promise, the trials offer limited data over a 48 week period. Early results do not guarantee long-term outcomes as the body learns to adapt to lower weight, reducing the rate of further weight loss. Biological changes in the body can oppose weight loss, especially where a lot has already been lost.

What is happening in phase 3?

TRIUMPH Phase 3 trials will look at evaluating the efficacy and safety of Retatrutide over a longer period of time (113 weeks) and across more patients. It will also look at the effect of the medication in patients with established cardiovascular disease and a history of unsuccessful weight loss through diet alone. These trials are expected to end in January 2026 with final results expected to be posted after.

Prior to approval, final results are needed to confirm what was established in phase 2 trials. Additionally, as these trials take place over a much longer course and encompass a wider, more diverse population, its safety must be determined in all these patient groups before it can be approved.

Retatrutide vs other weight loss medications

Retatrutide activates GLP-1, GIP and glucagon compared to Mounjaro which only activates GLP-1 and GIP and Wegovy which only activates GLP-1. Theoretically, Retatrutide can become the most effective treatment on the market due to this triple therapy.

STEP trials have found patients lost 15% of their mean body weight in 68 weeks using the maintenance dose of Wegovy (2.4mg).

SURMOUNT trials found patients lost between 20-22% of their mean body weight in 72 weeks using the highest dose of Mounjaro (15mg).

Current phase-2 trials for Retatrutide show weight loss results of 22-24% in just 48 weeks. Whilst this was a small trial, effects are currently highest when compared to other weight loss medications already on the market.

Safety and side effects of retatrutide

Common side effects reported with the medicine were gastrointestinal-nausea, vomiting, diarrhoea and constipation and occurred in a dose-dependent fashion.

Most of these occurred when the dose was increased. For this reason gradual dose escalation is preferred as this lets the body adjust to the effects of the medication, reducing the risk of side effects occurring. This is the same strategy used for other obesity medications currently on the market.

Phase 3 trials aim to delve deeper into the safety of the treatment by assessing how Retatrutide works over a longer period. They will also assess long-term safety, incidence of adverse effects and how the treatment would work in patients with other medical conditions.

Who might not be suitable if it is approved?

The exclusion criteria is expected to be similar to the two medications already on the market as all three now have at least 1 component in common (GLP-1). Patients may not be suitable for treatment if they have:

• Personal or family history of medullary thyroid cancer (MEN2)

• Severe kidney disease

• History of pancreatitis

• Known allergy to the drug or its ingredients

• Severe gastrointestinal disease - such as gastroparesis

• On interacting medication

• Are pregnant or breastfeeding

As with any treatment, it is important to discuss your health with a prescriber who is optimally placed to provide personalised advice.

Monitoring and aftercare

Parameters which would be monitored whilst on the treatment include:

• Weight and BMI

• Hydration levels

• Diet and exercise regimens

• Any side effects

• If relevant - ongoing contraception

Here at Quick Meds, our clinicians are available to help support patients at each step of their weight loss journey. If you experience side effects, we are at hand to offer tailored advice on how to manage these based on your individual journey.

UK status and availability

Currently, Retatrutide is not licensed or supplied by any regulated UK pharmacies, including Quickmeds. The medication is still in its clinical trial phase so exercise caution if you do find somewhere which claims to stock it.

Not only is it illegal, but it is also unsafe to use unregulated medicines purchased from social media or unofficial suppliers. These unapproved products may contain harmful ingredients or contaminants and may not even contain what they say they do.

There are several licensed weight loss medications available to help you lose weight safely. Wegovy, Mounjaro and Orlistat are all licensed with published data confirming safety profiles and how well they work. Ensure to approach a registered pharmacy, such as Quick Meds to obtain your treatment and for tailored evidence-based advise.

What to consider while you wait for final trial results

Whilst awaiting the final results from the trials, it's important to focus on evidence-based lifestyle measures and work with a healthcare professional to help you lose weight.

Eating a balanced diet, rich in fruits vegetables, whole grains and lean proteins can support overall health and aids in weight loss. Regular physical activity of moderate intensity alongside other lifestyle changes such as reducing alcohol intake and stopping smoking can all help you whilst you await the new treatment.

Additionally, you can work with a clinician to review currently licensed options that suit your medical history. Current treatments like Wegovy and Mounjaro have been proven in clinical trials to promote weight loss when used alongside a healthy diet and exercise plan.

Dosing and administration in trials

In clinical trials, Retatrutide was administered as a once-weekly injection with a stepwise increase from the lowest dose. As activation of the three different hormone receptors can cause gastric side effects, it is important to increase gradually, allowing the body to adapt. This strategy also helps to achieve the maximum efficacy whilst minimising side effects.

Importantly, trial dosing is not a prescribing guide, the doses used within are investigational. These doses are designed for research purposes to determine safety and efficacy. No official prescribing information exists at present.

Potential benefits beyond weight

Clinical trials have shown that Retatrutide can significantly reduce blood sugar levels in patients with obesity. In addition, a part of the phase 2 study demonstrated a reduction in liver fat, with 82% of participants achieving a liver fat content below 5% after 48 weeks of treatment.

Participants also experienced reductions in blood pressure, waist circumference, and lipid levels, suggesting that Retatrutide may be beneficial beyond weight loss, including potential cardiovascular risk reduction.

However, these findings are preliminary with long-term safety and efficacy yet to be established. The phase 2 study lasted only 48 weeks and the population was limited to adults with obesity. It did not account for diverse ethnic backgrounds or multiple comorbidities, highlighting the need for further research before broad conclusions can be drawn.

What retatrutide could mean for weight-related health conditions

Phase 2 trials have demonstrated a potential benefit in weight-related health conditions such as obesity and cardiovascular disease. With obesity remaining a risk factor for both, Retatrutide could offer a novel way forward in the management of these long-term conditions, potentially addressing them before they manifest into chronic conditions.

Importantly, individual response can vary due to biological differences, other co-morbid conditions and adherence to lifestyle factors. This highlights the importance of personalised treatment plans.

How Quick Meds can help now

Here at Quick Meds, we do not currently supply Retatrutide as it is still undergoing clinical trials. We do however, offer alternatives such as Mounjaro and Wegovy for eligible patients.

Our GPhC-regulated service can assess your health and offer pharmacist-led support on safe, effective weight management options in line with personalised lifestyle advice to help in your treatment journey.

All weight loss treatments are prescription only. For this reason, patients must complete an online consultation form prior to making a purchase. This is assessed by our clinicians who will review the order, offer tailored advice and sometimes request additional information to facilitate the order. Once approved, we can ship to most UK based addresses as soon as next day.

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