Retatrutide: the latest weight-loss drug — what do we know so far? | Goodweigh

Retatrutide: the latest weight-loss drug — how does it work and when will it be available?

Short answer: Retatrutide is a promising new weight-loss drug currently in phase 3 trials; as a triple agonist, it activates three hormone receptors simultaneously and has demonstrated weight loss of over 24%. It is not yet available in the Netherlands.

Retatrutide is a new weight-loss drug in development that goes further than semaglutide or tirzepatide. As the first “triple agonist”, it activates three hormone systems simultaneously: GLP-1, GIP and glucagon. In a phase 2 study published in the New England Journal of Medicine, retatrutide was found to achieve an average weight loss of over 24% after 48 weeks. Goodweigh explains what retatrutide is, how it works and what you can do now if you are looking for medically supervised weight loss.

What is retatrutide?

Retatrutide is an experimental drug from pharmaceutical company Eli Lilly that is administered as a weekly injection. It belongs to a new class of molecules that activate three hormone receptors simultaneously: GLP-1, GIP and glucagon. At present, retatrutide has not yet received approval from the FDA or EMA, and the ongoing Phase 3 trials under the name TRIUMPH-4 will determine the final approval decision. Retatrutide works via three hormone receptors simultaneously, as described in a review article in the European Journal of Clinical Pharmacology, which analyses the pharmacological basis of the substance in detail. The difference from previous generations is fundamental: whereas existing drugs target one or two receptors, retatrutide combines three complementary mechanisms in a single molecule.

How does retatrutide work?

Retatrutide influences energy metabolism via three separate but interrelated pathways simultaneously. Via GLP-1, it suppresses appetite and slows gastric emptying, keeping you feeling full for longer and reducing calorie intake. Via GIP, it supports insulin production and regulates fat storage, a mechanism that is also central to how tirzepatide works as a dual GLP-1/GIP agonist. The glucagon component adds a third dimension to this: it increases fat burning and total calorie expenditure, even at rest. Together, these three mechanisms create a synergistic effect that exceeds the sum of their individual actions.

What results has retatrutide shown?

The results from clinical trials are strikingly strong compared to previously approved drugs. In a phase 2 study published in the New England Journal of Medicine, retatrutide achieved an average weight loss of 24.2% at the highest dose of 12 mg after 48 weeks. In the ongoing TRIUMPH-4 phase 3 study, preliminary results of 28.7% were reported, corresponding to approximately 32 kilograms based on an average baseline weight. Published in The Lancet Diabetes & Endocrinology, a sub-study showed that retatrutide achieved a 17% weight loss in people with type 2 diabetes, combined with a 2.0 percentage point reduction in HbA1c and a reduction in liver fat of more than 80%.

How does retatrutide compare to semaglutide and tirzepatide?

The three drugs represent successive generations of weight-loss medication, each with a broader mechanism of action than the previous one. Semaglutide, the active ingredient in what semaglutide does to your appetite and weight, is a single GLP-1 agonist. Tirzepatide combines GLP-1 and GIP as a dual agonist. Retatrutide adds glucagon as a third component. A network meta-analysis of 29,506 participants showed that retatrutide consistently demonstrated greater weight loss than both its predecessors, although direct head-to-head randomised trials are still lacking.

The table below provides an overview based on available study data. Direct comparisons are not yet available; the figures are derived from separate studies with different populations and treatment durations.

What are the side effects of retatrutide?

The side effect profile of retatrutide is very similar to that of other GLP-1-based agents. Nausea, diarrhoea, constipation and vomiting are the most commonly reported effects, and they predominantly occur during the dose-titration phase at the start of treatment. A systematic review of the safety of retatrutide shows that most side effects are mild to moderate in nature and diminish as the body becomes accustomed to the higher dose.

With regard to side effects of GLP-1 medication, long-term data spanning several years are not yet available for retatrutide for any of the drugs in this class. Always discuss questions about safety and suitability with a doctor before considering treatment.

When will retatrutide be available in the Netherlands?

Retatrutide is not currently approved by the European Medicines Agency (EMA) and is therefore not legally available in the Netherlands. It is expected that an EMA application may be submitted by the end of 2026 or in 2027 following the completion of the phase 3 trials, but a definitive availability date is uncertain. The CBG-MEB, which implements EMA decisions in the Netherlands, has not yet opened an assessment procedure. Unregulated peptides offered online as “research chemicals” are dangerous: their purity, dosage and safety are unchecked, and their use is not medically supervised. For up-to-date information on which GLP-1 medication is already available and under what conditions you may be eligible for it, please visit the relevant page.

What are the best alternatives right now?

Anyone already seeking medically supervised weight loss does not need to wait. Tirzepatide, the active ingredient in Mounjaro, is EMA-approved and has shown weight loss of 15 to 22% in studies, bringing it closest to retatrutide of all current options. Semaglutide, available as Wegovy among other brands, has an extensive safety profile with years of real-world data and is the proven first choice for many patients. Both medicines are available on the Goodweigh platform, with supervision from a Dutch doctor. According to the Pharmacotherapeutic Compass, both medicines are indicated as an adjunct to a calorie-restricted diet and increased physical activity in adults with a BMI of 30 or higher, or 27 or higher in the presence of weight-related comorbidities.

How does Goodweigh support you with medical weight loss?

Goodweigh offers a fully digital programme: you start with an online intake assessed by a Dutch doctor, after which a personalised treatment plan is drawn up based on your health history and goals. Medication is discreetly delivered to your home, and throughout the programme you have access to coaching to help you make lifestyle changes alongside the medication. Read more about how Goodweigh supports you with medical weight loss and what the programme actually involves. Medical supervision significantly increases the effectiveness and safety of weight-loss medication compared to unsupervised use.

Don’t wait for retatrutide — start now with a proven treatment

Retatrutide is promising and the study results are impressive, but the drug won’t be available through regular medical channels in the Netherlands for years to come. Tirzepatide and semaglutide are now approved, have a proven safety record and are available through Goodweigh with professional medical supervision. For anyone who wants to tackle their excess weight now with medical support, these are the recommended choices. Start your intake today and discuss with a Goodweigh doctor which treatment best suits your situation.

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