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?

The short answer: Retatrutide is a highly promising new weight loss drug currently in phase 3 clinical trials. It is a so-called "triple agonist" that simultaneously activates three hormone receptors and has enabled weight loss of over 24 percent. 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 simultaneously activates three hormonal systems: GLP-1, GIP, and glucagon. In a phase 2 study published in the New England Journal of Medicine, retatrutide led to an average weight loss of over 24 percent after 48 weeks. Goodweigh explains what retatrutide is, how it works, and what you can do right now if you are looking for a medically supervised weight loss program.

What is retatrutide?

Retatrutide is an experimental drug developed by the pharmaceutical company Eli Lilly, administered as a weekly injection. It belongs to a new class of molecules that simultaneously activate three hormone receptors: GLP-1, GIP, and glucagon. Currently, retatrutide has not yet received marketing authorization from the FDA or the EMA, and the ongoing phase 3 trials, known as TRIUMPH-4, are critical for the final approval decision. Retatrutide acts simultaneously on three hormone receptors, as described in a review articlepublished in the European Journal of Clinical Pharmacology, which analyzes the pharmacological basis of this substance in detail. The difference from previous generations is fundamental: while existing drugs act on one or two receptors, retatrutide combines three complementary mechanisms into a single molecule.

How does retatrutide work?

Retatrutide affects energy metabolism through three separate but interdependent pathways simultaneously. Via GLP-1, it reduces appetite and slows gastric emptying, which helps maintain a feeling of fullness for longer and reduces calorie intake. Via GIP, it promotes insulin production and regulates fat storage – a mechanism that is also a key part of the mechanism of action of tirzepatide as a GLP-1/GIP dual agonist. The glucagon component adds a third dimension: it increases fat burning and total calorie expenditure, even at rest. Together, these three mechanisms produce a synergistic effect that is greater than the sum of their individual effects.

What results have been achieved with retatrutide?

The results of clinical trials are remarkably good compared to already 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 12 mg dose after 48 weeks. Preliminary results have been reported from the ongoing phase 3 TRIUMPH-4 trial, showing weight loss of 28.7%, which corresponds to approximately 32 kilograms from the average starting weight. A sub-study published in The Lancet Diabetes & Endocrinology showed that retatrutide led to a 17 percent weight loss in patients with type 2 diabetes, accompanied by a 2.0 percentage point decrease in HbA1c levels and a reduction in liver fat of over 80 percent.

How does retatrutide compare to semaglutide and tirzepatide?

These three medications represent successive generations of weight-loss drugs, each with a broader mechanism of action than its predecessor. Semaglutide, which is how semaglutide affects appetite and weight the active ingredient in the article, is a simple GLP-1 agonist. Tirzepatide combines GLP-1 and GIP as a dual agonist. Retatrutide adds glucagon as a third component to this. A network meta-analysis of 29,506 participants showed that retatrutide consistently led to greater weight loss than its two predecessors, although direct randomized comparative studies have not yet been conducted.

The table below provides a summary based on available research data. Direct comparisons are not yet available; the figures are taken from separate studies that examined different target groups 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 medications. Nausea, diarrhea, constipation, and vomiting are the most commonly reported side effects; these occur mainly during the dose-adjustment phase at the beginning of treatment. A systematic analysis of the safety of retatrutide shows that most side effects are mild or moderate and subside as the body adjusts to a higher dose.

Regarding the side effects of GLP-1-based medications, it is worth noting that while long-term data covering several years is available for all medications in this class, such data does not yet exist for retatrutide. Always discuss the safety and suitability of treatment with a doctor before starting.

When will retatrutide be available in the Netherlands?

Currently, retatrutide has not been granted marketing authorization by the European Medicines Agency (EMA), so it is not legally available in the Netherlands. An application for marketing authorization from the EMA will likely be submitted once Phase 3 trials are completed, possibly by the end of 2026 or in 2027, but the final market release date remains uncertain. The CBG-MEB, which implements EMA decisions in the Netherlands, has not yet begun an evaluation procedure. Unregulated peptides sold online as "research chemicals" are dangerous: their purity, dosage, and safety are not monitored, and their use is not supervised by a doctor. Check up-to-date information on GLP-1 medications already available and the requirements for their use.

What are the best options right now?

If you are looking for a medically supervised weight-loss program right now, you do not need to wait. Tirzepatide, the active ingredient in Mounjaro, is EMA-approved, and in studies, it has shown 15–22 percent weight loss, making it the closest of all current options to retatrutide. Semaglutide, available under names such as Wegovy, has demonstrated an established safety profile thanks to years of clinical use and is a proven first-choice option for many patients. Both of these medications are available On the Goodweigh platform under the supervision of a Dutch doctor. According to the medication guide these two medications are recommended as an adjunct to a reduced-calorie diet and increased physical activity for adults with a BMI of ≥ 30, or ≥ 27 if they have weight-related comorbidities.

How does Goodweigh support you in medically supervised weight loss?

Goodweigh offers a fully digital treatment pathway: you start by completing an online questionnaire, which is reviewed by a Dutch doctor, after which a personalized treatment plan is created based on your health data and goals. The medication is delivered discreetly to your home, and throughout the program, you receive support to help you change your lifestyle alongside the medication. Learn more about how Goodweigh supports you in medically supervised weight loss and what this program actually consists of. Medical supervision significantly increases the effectiveness and safety of weight-loss medications compared to unsupervised use.

Don't wait for retatrutide. Start a proven treatment today

Retatrutide is a promising medication with impressive research results, but it will not be available through standard medical channels in the Netherlands for several years. Tirzepatide and semaglutide are now approved, their safety is proven, and they are available through Goodweigh with professional medical support. For those who want to tackle excess weight with medical support right now, these are the most suitable options. Start your initial consultation today and discuss the treatment best suited to your situation with a Goodweigh doctor.

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