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 become 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 at once and has demonstrated weight loss of over 24%. It is not yet available in the Netherlands.

Retatrutide is a new weight-loss drug under development that goes further than semaglutide or tirzepatide. As the first ‘triple agonist’, it activates three hormonal systems at once: GLP-1, GIP and glucagon. In a phase 2 study published in the New England Journal of Medicine, retatrutide was shown to achieve an average weight loss of more than 24% after 48 weeks. Goodweigh explains what retatrutide is, how it works, and what you can already do if you are seeking medically supervised weight loss.

What is retatrutide?

Retatrutide is an experimental drug from the pharmaceutical company Eli Lilly, administered as a weekly injection. It belongs to a new class of molecules that activate three hormone receptors at once: 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 are crucial to the final approval decision. Retatrutide acts via three hormone receptors simultaneously, according to a review article in the European Journal of Clinical Pharmacology, which analyses the drug’s pharmacological basis in detail. The difference compared to previous generations is fundamental: whereas existing agents affect one or two receptors, retatrutide combines three complementary mechanisms in a single molecule.

How does retatrutide work?

Retatrutide affects energy metabolism via three separate but interconnected pathways simultaneously. Via GLP-1, it suppresses appetite and delays gastric emptying, meaning that one remains full for longer and consumes fewer calories. 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: 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 effects.

What results does retatrutide show?

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

How does retatrutide compare to semaglutide and tirzepatide?

The three drugs represent successive generations of weight-loss medicines, 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 simple 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 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 taken 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 medicines. Nausea, diarrhoea, constipation and vomiting are the most commonly reported side effects, and they occur mainly 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 and subside as the body adjusts to the higher dose.

As with side effects of GLP-1 medicines, it is the case for all drugs in this class that long-term data spanning several years are not yet available for retatrutide. Always discuss questions regarding safety and suitability with a doctor before considering treatment.

When will retatrutide become 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, following the completion of phase 3 trials, may be submitted in late 2026 or in 2027, but a definitive availability date is uncertain. The CBG-MEB, which implements the EMA’s decisions in the Netherlands, has not yet initiated an assessment procedure. Unregulated peptides sold online as ‘research chemicals’ are dangerous: their purity, dosage and safety are unchecked, and they are used without medical supervision. Click here for up-to-date information on which GLP-1 medicines are already available, and under what conditions you are eligible for them.

What are the best alternatives right now?

If you are already seeking medically supervised weight loss, you don’t need to wait. Tirzepatide, the active ingredient in Mounjaro, is approved by the EMA and has shown weight loss of 15 to 22% in studies, making it the closest to retatrutide of all current options. Semaglutide, available as Wegovy among other brands, has a comprehensive safety profile with many years of real-world data and is the proven first choice for many patients. Both medicines are available on the Goodweigh platform with guidance from a Dutch doctor. According to Farmacotherapeutisch Kompas, both agents are indicated as an adjunct to a calorie-restricted diet and increased physical activity in adults with a BMI of 30 or above, or 27 or above in the presence of weight-related comorbidities.

How does Goodweigh guide you through medical weight loss?

Goodweigh offers a fully digital programme: you start with an online initial assessment, which is reviewed by a Dutch doctor, after which a personalised treatment plan is drawn up based on your medical history and your goals. The medication is delivered discreetly to your door, and throughout the programme you have access to coaching to help you make lifestyle changes alongside the medical treatment. Read more about how Goodweigh guides you through medical weight loss and what the programme specifically entails. Medical guidance 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 standard medical channels in the Netherlands for many years. Tirzepatide and semaglutide are now approved, proven to be safe and available through Goodweigh with professional medical guidance. For those who wish to address their weight with medical support, these are the right choices. Start your initial consultation today and discuss with a Goodweigh doctor which treatment best suits your situation.