The next generation of glucagonlike peptide 1 (GLP-1) weight-loss drugs has taken another step forward to U.S. Food and Drug Administration approval. In new clinical trial results from the pharmaceutical company Eli Lilly, a weekly injection of 12 milligrams (0.19 grain) of retatrutide for 80 weeks helped people lose almost 30 percent of their body weight—about 70 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, [with] the greatest weight loss,” he says.
Unlike other approved GLP-1 medications, Wegovy and Zepbound, which also target the gut hormone 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. For example, tirzepatide (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 new retatrutide study is a phase 3 clinical trial—the gold standard needed to secure eventual FDA approval—called TRIUMPH-1. The participants were all classified as either overweight or having obesity, with an average baseline weight of 248.5 pounds. At the highest doses of retatrutide tested—12 milligrams (0.19 grain)—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, an executive vice president of Eli Lilly 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 about a quarter reported constipation. Between 10 percent and a quarter experienced vomiting, depending on the dose. These effects were in line with expectations, Drucker says.
“If it’s approved..., this would be the drug that people who need to lose the most amount of weight would gravitate to,” he adds.