A phase 3 clinical trial for a new weight-loss drug funded by Eli Lilly found that using retatrutide “resulted in significant weight reduction,” as well as other improvements among participants.
The findings, published September 29 in the National Library of Medicine, come as demand for anti-obesity medications continues to grow and drugmakers race to expand treatment options beyond existing GLP-1 therapies such as Wegovy and Ozempic. Interest in next-generation treatments like retatrutide has increased as researchers investigate whether they can produce even greater weight loss while addressing obesity-related conditions including sleep apnea and osteoarthritis.
“This is another future tool in the tool belt in managing obesity with impressive results,” Dr. Brian Wojeck, a Yale Medicine endocrinologist and assistant professor at Yale School of Medicine, told Newsweek on Wednesday. “We will continue to get different tools to treat this important patient population. This is just the beginning.”
What Is Retatrutide?
Retatrutide is a weight-loss drug that targets three hormone receptors instead of the hormone, GLP-1, that is targeted with popular brands such as Wegovy and Ozempic. Whereas drugs such as Wegovy and Ozempic mimic the GLP-1 hormone to help people feel full for longer and therefore eat less, retatrutide targets the hormones GIP and glucagon in addition to GLP-1. Researchers believe that the added glucagon activity may help increase energy expenditure and fat burning, which could contribute to the larger weight loss seen in clinical trials.
In the Eli Lilly clinical trial, retatrutide was administered by injection. GLP-1 drugs also can be administered by injection, and tablets taken once daily are also available from Wegovy. The U.S. Food and Drug Administration (FDA) approved the first GLP-1 pill late last year.
What Eli Lilly Has Said About Clinical Trials
The Eli Lilly clinical trial studied 2,339 adults with obesity who did not have diabetes over 18 months. Some of the participants also had knee osteoarthritis and obstructive sleep apnea. Trial participants were randomly assigned to receive either a 4-milligram dose of retatrutide, a 9-milligram dose, a 12-milligram dose or a placebo.
Researchers found “significant weight loss” among the participants who took the retatrutide dose. The average change in body weight in the retatrutide groups was a 17.6 percent reduction for those in the 4-milligram dose group, 23.7 percent in body weight for the 9-milligram dose and 25 percent for the 12-milligram dose. Participants who took the placebo had a 3.9 percent reduction in body weight.
“This is the most effective agent in published trial. However, there are many other drugs in study,” Wojeck said. “I am hopeful that we will only get better at treating obesity effectively and safely over time.”
Despite the positive results of retatrutide, Novo Nordisk Executive Vice President and Chief Science Officer Dr. Martin Holst Lange said in June that the company, which manufactures Ozempic, is exploring potential treatments that could compete with the new drug, according to a report by Fierce Biotech.
In the retatrutide study by Eli Lilly, participants with knee pain or sleep apnea who were taking the retatrutide doses also saw improvement.
“In adults with obesity, retatrutide resulted in significant weight reduction, reduced pain in participants with knee osteoarthritis, and reduced apnea-hypopnea events in participants with obstructive sleep apnea,” according to trial results.
Common side effects were gastrointestinal in nature.
When Could Retatrutide Be Approved?
Retatrutide remains experimental and has not been approved by the FDA. Eli Lilly is likely to seek regulatory approval after its positive phase 3 trials, but an approval date has not been announced. Additional trials are underway.
Newsweek reached out to the FDA by email for comment on Wednesday.
“Retatrutide has not been approved by any regulatory agency and is legally available only through Lilly’s clinical trials,” Eli Lilly said on its website. “Anything sold to consumers outside of those trials is illegal, with no way to verify its safety, purity or dosing. Taking unregulated substances poses serious health risks and Lilly continues to work with law enforcement and regulatory authorities to combat black market drugs.”
Why Are People Buying It Before Approval?
Despite retatrutide not having been federally approved, people are still accessing it online, at convenience stores and even through medical professionals, CBS News reported.
Eli Lilly stressed that retatrutide is investigational and urged people not to take any product claiming to be retatrutide unless they were partaking in a Lilly trial.
“Illicit retatrutide products may contain unknown ingredients, harmful contaminants and impurities,” Eli Lilly warned on its website. “These products may also have too much or too little active ingredient, or the wrong ingredient entirely. Lilly continues to warn the public about the dangers of unapproved drugs.”
Wojeck also urged against public use of the drug at this point.
“Obesity physicians generally strongly recommend against using compounded agents as they have not been studied and are associated with increased adverse events including hospitalization,” he said. “I certainly do not manage compounded agents.”
What We Know About Reported Deaths
Two people have died after allegedly taking a drug claiming to be retatrutide sold on the black market, according to reports sent to the FDA, CBS News reported. One death occurred in July after a woman with obesity experienced cardiac arrest. Another person died in September after buying a product claiming to be retatrutide online after a nurse allegedly convinced her to do so, CBS News reported.
The deaths were not connected to Eli Lilly’s trial, the report said.
Contact Newsweek editors on this story: Kate Nalepinski and Dave Siminoff.