The Pages section of GPnotebook comprises more than 30,000 concise, interlinked clinical reference articles, each focused on a specific primary care topic.
There has been plenty of recent coverage of retatrutide, a medicine still in clinical trials that has also inspired illegal black-market products. Nicknamed “Reta” – and, more unhelpfully and stigmatisingly, the “Godzilla jab” – these illegal products have appeared across the Republic of Ireland and Northern Ireland, as well as in many other countries.
Retatrutide itself is not approved for human use and is not expected to become available until 2027 or 2028. Yet, we already need to understand both the investigational medicine and the unregulated products circulating in our communities. These products are being acquired illegally, manufactured illegally and sold online, through social media and via networks such as gyms, often as weight-loss or aesthetic treatments.
Specialists working in the area of obesity, the manufacturer and the Health Products Regulatory Authority have all warned about the risks of these unregulated products. Hospitalisations have been reported, including for gastrointestinal and renal complications. There is also the issue of whether the product that the person has acquired actually contains the retatrutide molecule, what dose it is at, and what it could potentially be mixed with. As GPs, we may be the first to suspect that a patient is using illegal “Reta”. Patients may also trust us enough to raise it directly, giving us an opportunity to advise against unsafe, unregulated and unsupervised use.
It is important to distinguish these products from retatrutide itself. A recently updated GPnotebook page summarises what we currently know about the investigational medicine retatrutide as it awaits licensing and official distribution.
Retatrutide is a single-agent tri-agonist at the glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon receptors. We are familiar with GLP-1 receptor agonists, which act at one receptor, and may also know about tirzepatide, which acts at the GLP-1 and GIP receptors. Evidence to date has focused on retatrutide’s potential in obesity and type 2 diabetes.
In a phase 2 obesity study, more than 90% of participants receiving 12 mg once weekly lost at least 10% of baseline weight, nearly two-thirds at least 20%, nearly half at least 25%, and one-quarter at least 30%. Mean weight change at 24 weeks was −7.2% with 1 mg, −12.9% with 4 mg, −17.3% with 8 mg and −17.5% with 12 mg, compared with −1.6% for placebo. The most common adverse events were transient, mainly mild-to-moderate gastrointestinal symptoms, particularly during dose escalation.
In a phase 2 trial in people with type 2 diabetes, HbA1c reductions were significantly greater than with placebo at all doses except 0.5 mg once weekly, and greater than with dulaglutide 1.5 mg once weekly at the 8-mg and 12-mg doses. The trial also reported lower systolic and diastolic blood pressure, reduced non-HDL-cholesterol and lower triglycerides.
It is worth keeping the trial phases in mind. Early-phase trials (phases 0–2) mainly assess safety, dosing and adverse effects. Phase 3 typically asks whether a new treatment performs better than current options, while phase 4 follows licensing and examines longer-term effects. Retatrutide’s phase 3 trials are expected to complete in late 2026. For now, it is certainly not a medicine anyone should be taking outside a clinical trial.
Where we have a person living with obesity who asks for our advice, this page gives an evidence-based introduction to the chronic condition of obesity, its complications, its assessment and some of the treatment options. It also links to a range of practical resources covering different aspects of obesity management.
The pages here and here also contain some useful practice points on recent developments in safe prescribing of GLP-related medications, relating to pregnancy, contraception, breastfeeding and HRT, which are hot topics in this area.
On a related note, I also found this recently updated page on visceral fat useful. It explains the clinical implications and includes useful facts for conversations with patients about weight, lifestyle and cardiovascular health.
So, there we have it: an update on the promising investigational medicine retatrutide, how it works and where the evidence currently sits, alongside the much less positive story of the separate, illegal copycat product known as “Reta”.
Some of our patients may already be using “Reta” without supervision and experiencing effects from either the compound itself or unknown substances mixed with it. It is worth keeping our antennae up and having clear, sensible information ready to share.