3 min readEli Lilly just announced phase 3 clinical trial results for its new medication, retatrutide, and it could become the most effective weight loss medication yet.Retatrutide is a triple-agonist medication, meaning it activates three hormone receptors involved in appetite and metabolism: GLP-1, GIP, and the glucagon receptor.While exciting, doctors stress that there are still side effects to consider, more research is needed, and this medication is not yet FDA-approved.
People who don’t get the weight loss results they’re after on a GLP-1 medication like Wegovy (semaglutide) may switch to a dual-agonist drug like Zepbound (tirzepatide) under the guidance of their doctor. And because the latter medication works on two different receptors in the body, it may lead to greater weight loss. Well, there’s now a triple-agonist medication waiting in the wings, and its clinical trial results are pretty impressive.
Eli Lilly, which makes Zepbound and Mounjaro, just announced phase 3 clinical trial results for its new medication, retatrutide, and it could become the most effective weight loss medication.
This medication is not yet FDA-approved, but retatrutide is already getting a ton of buzz. So, what’s the deal and how is it different from what’s currently available? Weight loss physicians explain.
Meet the experts: Mir Ali, MD, is the medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA. Gitanjali Srivastava, MD, is co-director of Vanderbilt Weight Loss Clinics.
What is retatrutide?
Retatrutide is a triple agonist medication, which means that it works on three different hunger-regulating hormone receptors on the body. This is a GIP, GLP-1, and glucagon triple hormone receptor agonist.
To put that into perspective, Ozempic and Wegovy are GLP-1 receptor agonists, while Zepbound and Mounjaro are dual GIP/GLP-1 receptor agonists. Like these medications, retatrutide is a drug you inject once a week.
Retatrutide is not approved yet by the Food and Drug Administration (FDA) for use by the general public.
What did the clinical trial find?
The clinical trial followed more than 400 people with obesity and knee osteoarthritis. People who participated in the trial either took a nine milligram or 12 milligram dose of retatrutide once a week for 68 weeks.
Overall, retatrutide lowered weight by up to an average of 28.7 percent (or 71.2 pounds). It also reduced pain by up to an average of 4.5 points (or 75.8 percent).
For comparison, a separate study in The New England Journal of Medicine that compared tirzepatide and semaglutide over 72 weeks found people who took tirzepatide lost an average of 50 pounds or about 20.2 percent of their body weight. Participants who took semaglutide lost an average of 33 pounds or 13.7 percent of their body weight.
Related StoriesWhy is this significant?
While there are already great weight loss medications on the market that have given plenty of people success, “it doesn’t hurt to have other alternatives,” says Mir Ali, MD, medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA.
As for this specific alternative, the weight loss results are “remarkable” so far, says Gitanjali Srivastava, MD, co-director of Vanderbilt Weight Loss Clinics. The data “highlight retatrutide as a potential breakthrough therapy,” she says.
Dr. Srivastava flags the gastrointestinal side effects—like many of these medications, some people had nausea, diarrhea, constipation, and vomiting—but says that the “robust” weight loss makes this an attractive option for people with severe obesity who also have knee arthritis. “It holds particular promise for those seeking deeper weight loss and broader health gains,” she adds. However, some doctors say lower doses may be considered for people seeking more modest weight loss, too.
But Dr. Ali also points out that more research is needed. “We still need to see a long-term side effect profile,” he says.
Also, it’s worth noting that these medications are still the most effective when they’re used forever, which is tricky from a cost and weight loss maintenance perspective. “It is common for patients to regain weight when they stop these medications,” he says. “If patients don’t make significant long-term changes to their diet and lifestyle, nothing will change.”
Korin Miller is a freelance writer specializing in general wellness, sexual health and relationships, and lifestyle trends, with work appearing in Men’s Health, Women’s Health, Self, Glamour, and more. She has a master’s degree from American University, lives by the beach, and hopes to own a teacup pig and taco truck one day.