A new drug called retatrutide, developed by pharmaceutical company Eli Lilly, has demonstrated the ability to help some obese individuals with type 2 diabetes lose up to a quarter of their body weight while effectively managing blood sugar levels. The medication operates by mimicking the effects of three different hormones to regulate appetite, control glucose, and boost metabolism.
Unlike existing GLP-1 receptor agonists, which typically mimic one or two hormones, retatrutide targets three, offering a novel approach. However, it has not yet received regulatory approval in the UK. The pivotal phase of testing, known as the TRIUMPH-2 trial, was conducted across 92 sites in eight countries and involved over 2,000 participants. All trial members had a body mass index (BMI) greater than 27 and type 2 diabetes.
Participants were randomly assigned to receive varying doses of retatrutide-4mg, 9mg, or 12mg-or a placebo. After 80 weeks, those taking 4mg lost an average of 11.9% of their body weight, increasing to 16.8% with the 9mg dosage, and reaching 18.8% with the 12mg dose. By comparison, the placebo group lost an average of 5.1%.
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Remarkably, nearly half (47%) of those on the highest dose lost at least 20% of their initial weight, while 31% lost a quarter or more. In contrast, only 6% and 3% of the placebo group reached these milestones, respectively. Additionally, 72% of people receiving retatrutide achieved an HbA1c level of 6.5% or lower-the threshold used by the NHS to diagnose diabetes-compared with just 29% of those on placebo.
The trial reported common side effects such as diarrhoea and nausea. There were seven deaths during the study-spread across different dosage groups and one in the placebo group-but these were determined to be unrelated to the medication.
Researchers described the findings as a significant advancement for treating obesity and type 2 diabetes, conditions that have often been difficult to manage through weight loss alone. They noted that retatrutide not only substantially reduced body weight but also improved blood sugar control and other cardiometabolic risk factors, with a safety profile consistent with other GLP-1 receptor agonists. Further research is needed to assess whether these improvements translate into benefits for other obesity-related health complications.
The results are due to be presented at the upcoming European Association for the Study of Diabetes (EASD) annual meeting in Milan and published in The Lancet.
In a related study also presented at EASD, another investigational drug, petrelintide, showed promising results by helping participants lose more than 10% of their body weight with fewer side effects. Petrelintide, administered once weekly, mimics the natural pancreatic hormone amylin, which promotes a feeling of fullness. This could offer an option for patients who are unable to tolerate GLP-1 drugs.
This separate trial involved 485 participants across 32 sites in the United States, Poland, and Romania. Participants received doses ranging from 1.0mg to 9.0mg, with average body fat percentage reductions between 8.7% and 10.2%, depending on the dose. Nausea was the most commonly reported side effect, though most patients were able to tolerate dose escalation. Researchers suggest that amylin-based therapies like petrelintide may improve patient experience and adherence by reducing side effects compared to other obesity treatments.