While drugs such as Wegovy target a single gut hormone, retatrutide is among a new class of GLP-1 drugs that aims at three hormone receptors
By Adam Kovac edited by Claire Cameron
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The next generation of GLP-1 weight loss drugs has taken another step forward to U.S. Food and Drug Administration (FDA) approval. In new clinical trial results from pharmaceutical company Eli Lilly, a weekly injection of retatrutide for 80 weeks helped people lose about 30 percent of their body weight—about 85 pounds on average—according to a statement from the company.
That puts retatrutide essentially on a par with bariatric surgery, says Daniel Drucker, a university professor of medicine at the University of Toronto, who has previously consulted for Eli Lilly but was not involved in the trial. "This has always been the GLP-1 medicine that we have viewed as the most potent, the greatest weight loss," he says.
Unlike other approved GLP-1 medications, Wegovy and Zepbound, which also target the gut hormone glucagon-like peptide-1 (GLP-1), retatrutide targets three receptors known to regulate appetite—GLP-1, glucagon, and glucose-dependent insulinotropic polypeptide (GIP). Targeting more than one receptor seems to boost the medications' weight-loss effects. Tirzepatide, for example, which is sold under the brand name Zepbound, targets two receptors, and clinical trials suggest it helps people lose more weight than semaglutide (the active ingredient in Wegovy), which only targets one.
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The study is a phase III clinical trial—the gold standard needed to secure eventual FDA approval. The participants were all classified as either overweight or obese, with an average baseline weight of 248.5 pounds. At the highest doses of retatrutide tested—12 milligrams—participants lost 28.3 percent of their weight on average.
"TRIUMPH-1 highlights the importance of options and the potential for retatrutide to help people across various stages of their obesity journey," said Kenneth Custer, executive vice president and president of Lilly Cardiometabolic Health in a statement.
The results also highlighted potential side effects: about a third of participants reported nausea or diarrhea, while others reported constipation. Between 10 percent and a quarter suffered from vomiting. These are in-line with expectations, says Drucker.
"If it's approved... this would be the drug that people who need to lose the most amount of weight would gravitate to."
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