There might soon be a new weight loss treatment king on top. This week, Eli Lilly posted the first large-scale trial results of its experimental combination drug retatrutide—and it’s a whopper of a success.
Retatrudide. Say that fast five times. Okay, sure, it doesn’t exactly roll off the tongue, but as a weight loss medication, it’s kicking ass in clinical trials. According to the company, people with obesity and knee osteoarthritis taking retatrutide lost up to 71 pounds on average, or nearly 30% of their baseline weight. The weight loss results appear to be the best ever documented for an obesity medication so far and should pave the way toward retatrutide’s regulatory approval in the near future.
“We are encouraged by the results of TRIUMPH-4, which highlight the powerful effect of retatrutide, a first-in-class triple agonist, on body weight, pain and physical function,” said Kenneth Custer, executive vice president at Eli Lilly and president of Lilly Cardiometabolic Health, in a statement from the company.
A triple whammy
Drugs like semaglutide (the active ingredient in Ozempic and Wegovy) have greatly improved obesity treatment in recent years, allowing people to lose significantly more weight than they typically would with diet and exercise alone. Semaglutide and similar medications mimic the GLP-1 hormone, which plays an important part in regulating our hunger and metabolism. But there are other hunger-related hormones besides GLP-1, and some companies and research teams have developed drugs that combine these hormones together in hopes of achieving even greater effectiveness.
Eli Lilly’s tirzepatide (the active ingredient in Zepbound and Mounjaro) mixes GLP-1 with the hormone GIP, for instance. In a head-to-head comparison, tirzepatide (first approved in 2022) has indeed performed better than semaglutide at treating obesity. Retatrutide takes things up one more notch, combining three gut hormone agonists: GLP-1, GIP, and glucagon.
The TRIUMPH-4 trial of retatrutide involved 445 participants with obesity and knee osteoarthritis, with 84% having a body mass index of 35 and over (the criteria for severe obesity). They were randomized into three groups for 68 weeks: one taking a placebo, and the other two on different once-weekly doses of retatrutide.
By the study’s end, people who stayed on the highest dose lost an average of 28.4% of their baseline weight, amounting to 71 pounds, while those on the lower dose lost an average of 26.4% body weight (the placebo group lost an average of 2.1%). Both treatment groups also reported a significantly greater improvement in knee pain and physical function than the placebo group, as well as an improvement of cardiovascular risk factors, such as lower blood pressure.
The future of retatrutide
The company plans to release results from other Phase III studies of retatrutide over the next year. And barring any unexpected complications, these trial results should lead to a relatively easy approval of the drug from the FDA and other agencies.
No drug comes without its side effects, however, and retatrutide isn’t an exception. Similar to other GLP-1 drugs, many people taking retatrutide experienced gastrointestinal symptoms. About 43% on the highest dose reported nausea, for instance, while 33% reported diarrhea. And while the drug’s safety profile appears to be in line with approved GLP-1 drugs, at least some people discontinued taking retatrutide due to the drug’s adverse effects.
Eli Lilly reported a discontinuation rate of roughly 18% for the highest dose group and a 12% rate for the lower dose group. Some people also reported that they stopped taking the drug expressly because they were worried about “perceived excessive weight loss,” according to the company. For an imperfect comparison, the discontinuation rate seen in the landmark SELECT trial for semaglutide was around 17%.
These findings suggest that retatrutide isn’t going to be for everyone. Some potential users may not be able to tolerate the side effects or may simply not need or want to lose that much weight. But Eli Lilly seems to be aware of that, given its added focus on people with severe obesity and weight-related health problems like knee osteoarthritis. And for these higher-risk groups, retatrutide could certainly become the most promising drug seen yet—one that might even match the typical effectiveness of bariatric surgery.
Retatrutide isn’t the only next-generation obesity drug set to arrive in the near future. But it may take the mantle of the most potent medication available soon enough.