Key facts
- Retatrutide, a triple-hormone obesity drug, led to an average weight loss of 25% after 80 weeks in a trial.
- After an extension to 104 weeks, participants lost an average of 30% of their body weight.
- Over a third of participants lost 30% or more of their weight.
- The drug reduced knee pain by up to 62% in participants with obesity-linked knee osteoarthritis.
- Retatrutide reduced sleep apnea events by up to 57% in participants with obesity-linked obstructive sleep apnea.
- The trial included 2,339 participants across 11 countries.
Researchers have published late-stage clinical trial data for retatrutide, a new obesity drug that simulates three hormones: GLP-1, GIP, and glucagon. The results indicate it may be the most powerful weight-loss drug yet.
In the trial, which began in 2023 and included 2,339 participants across 11 countries, patients on the highest dose of retatrutide lost an average of 25% of their body weight after 80 weeks. This figure rose to an average of 30% after an extension period to 104 weeks. More than a third of participants achieved a weight loss of 30% or more.
The drug also demonstrated significant benefits beyond weight loss. In a subset of participants with obesity-linked knee osteoarthritis, retatrutide reduced knee pain by up to 62%. For those with obesity-linked obstructive sleep apnea, it decreased sleep apnea events by up to 57%. Cardiometabolic measurements, including blood pressure, triglycerides, and LDL cholesterol, also improved across the board. Furthermore, among participants with prediabetes at the start of the trial, over 90% saw their condition resolve by the end.
Retatrutide is being developed by Eli Lilly and builds upon existing GLP-1 and GLP-1/GIP based drugs like semaglutide (Ozempic/Wegovy) and tirzepatide (Zepbound/Mounjaro). It works by mimicking the actions of GLP-1, GIP, and glucagon, hormones that play roles in regulating blood sugar, appetite, and metabolism.
Common side effects reported were mild to moderate gastrointestinal issues such as nausea, diarrhea, and constipation, similar to those seen with existing obesity drugs. Some participants experienced dizziness and low blood pressure. The trial was not large enough to definitively assess rarer risks like cardiovascular events or pancreatitis, and further larger, longer trials are needed.