Eli Lilly has announced that its experimental drug retatrutide led to an average weight loss of up to 28.3% in a phase three trial, surpassing results from other obesity medications currently on the market. The once-weekly injection, a triple hormone receptor agonist, helped participants lose an average of 70.3 pounds over 80 weeks at the highest dose.
The trial involved 2,339 adults with obesity or overweight and at least one weight-related comorbidity, but without diabetes. Participants were randomly assigned to receive doses of 4mg, 9mg, 12mg, or a placebo. Those on the 12mg dose achieved the greatest weight loss, with 45.3% losing at least 30% of their body weight. The 9mg group lost an average of 64.4 pounds (25.9%), while the 4mg group lost 47.2 pounds (19.0%).
Dr Susan Spratt, an endocrinologist at Duke Health, described the results as the largest weight loss ever seen in any medication trial. The drug also helped 65.3% of participants on the highest dose reduce their BMI below 30, the clinical threshold for obesity, including 37.5% of those who started with a BMI of 40 or higher.
Retatrutide targets three hormones: GLP-1, GIP, and glucagon, the latter of which is not present in other weight-loss drugs like Wegovy or Zepbound. This combination is thought to improve metabolism and appetite control. However, side effects were common, with nausea affecting up to 42.4% of those on the highest dose, compared to 14.8% on placebo. Diarrhoea, constipation, and vomiting were also reported more frequently in the treatment groups.
The study also noted improvements in cardiovascular risk factors, including HDL cholesterol. Dr Ania Jastreboff, the lead researcher from Yale School of Medicine, emphasised that retatrutide produced clinically meaningful weight reduction for nearly all participants and improved cardiometabolic health measures.
