An experimental drug led to an average loss of one-quarter of the initial body weight at the highest dose studied.
Retatrutide is administered by an injection under the skin once a week. It acts on three hormonal systems linked to appetite and metabolism: GIP, GLP-1 and glucagon. Other obesity treatments already target one or two of these pathways, but this molecule combines all three.
Illustrative image from Pexels
The phase 3 trial included 2,339 adults with obesity who did not have diabetes. For 80 weeks, participants received either retatrutide at 4, 9 or 12 mg, or a placebo. Neither the participants nor the teams responsible for monitoring them knew which treatment was being administered.
At the end of the 80 weeks, the average weight loss reached 17.6% with 4 mg, 23.7% with 9 mg and 25.0% with 12 mg. The placebo group lost an average of 3.9%. These figures correspond to the analysis published in the New England Journal of Medicine, which takes the participants’ entire course into account.
To give some perspective, losing 25% of an initial weight of 100 kg corresponds to 25 kg. The response varied from person to person, as in most weight-loss trials.
The study did not focus solely on the scales. Among participants with knee osteoarthritis, the researchers also measured a reduction in pain. In those with obstructive sleep apnea, the number of interruptions or reductions in breathing during the night also decreased.
The most common adverse effects involved the digestive system. This type of problem is already known with other drugs that act on similar hormonal pathways. Monitoring tolerability therefore remains important, particularly at the highest doses.
Retatrutide is not yet a medication available in pharmacies. It remains experimental and has not been approved by any health authority. Eli Lilly is continuing its phase 3 program for obesity and several related diseases before applying for marketing authorization.
The next steps will therefore focus as much on safety as on long-term effectiveness. Researchers will need to clarify, in particular, how durable the weight loss is after several years and what happens when treatment is discontinued.