Experimental Weight-Loss Drug Retatrutide May Be More Effective Than Ozempic
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Eli Lily’s experimental new weight-loss drug is showing promising results.
Retatrutide, which just completed a phase 2 clinical trial, helped patients lose an average of 24% of their body weight.
The drug improves on existing weight-loss medications like Wegovy.
Weight-loss drugs like Wegovy, Mounjaro, and type 2 diabetes drug Ozempic have been all over headlines and social media. The drugs are so popular that all three injectables are currently in shortage in the U.S., indicating that there’s a huge demand for this kind of medication. Now, it seems, there’s another one in the works known as retatrutide—and it’s showing huge promise.
New phase 2 clinical trial results for Eli Lily’s experimental drug show that the medication may be even more effective than Ozempic and other predecessors. The study, which was published in The New England Journal of Medicine, followed 338 adults with obesity who took retatrutide injections or a placebo for 48 weeks. At the end of the study, the researchers found that people in the retatrutide group who took the highest dose (12 milligrams a week) lost around 24% of their body weight, compared to those in the placebo group, which lost 2% of their body weight.
Also worth noting: about a quarter of patients who took the 12 mg dose lost more than 30% of their body weight by 48 weeks. The conclusion was simple, with researchers noting that adults with obesity who took retatrutide had “substantial reductions in body weight.”
“It is striking that on average, participants with obesity taking the highest dose of retatrutide lost nearly a quarter of their body weight, on average 58 lbs with 11 months of treatment,” says lead study author Ania M. Jastreboff, M.D., Ph.D., director of the Yale Obesity Research Center. “Additionally, participants had not yet reached a weight plateau at the time the study was stopped. Meaning their weight was still decreasing rather than at steady state.”
But what is retatrutide and how does it work and is it for anyone looking to lose weight? Here’s what you need to know.
What is retatrutide and how does it work?
It’s important to note that retatrutide is still an experimental drug that’s being studied. Meaning, you can’t be prescribed it at this time. However, it definitely shows promise.
Retatrutide is a glucagon-like peptide-1 (GLP-1) agonist, like Wegovy and Ozempic. But, while it works similarly to those drugs, it also acts on two additional hormones: glucose-dependent insulinotropic polypeptide (GIP), which helps manage blood sugar, and glucagon, which can help suppress appetite and burn more energy.
“It’s what we call a triagnost medication,” says Kunal Shah, M.D., an assistant professor in the division of endocrinology at the Rutgers Robert Wood Johnson Medical Center. “Mounjaro is a dual agonist—it has a GLP-1 portion and a GIP. Wegovy is just a GLP-1. Researchers keep adding these elements and we’re seeing more efficient weight loss.”
“The results published in the study are amazing,” says Scott Keatley, R.D., co-owner of Keatley Medical Nutrition Therapy. Keatley also noted that study participants had reductions in A1C (a measure of blood sugar levels), blood pressure, and LDL (“bad”) cholesterol, in addition to weight loss.
Retatrutide side effects
The study cited some side effects of taking retatrutide, and they tended to be more intense at higher doses. Those included:
Nausea
Diarrhea
Vomiting
Constipation
The researchers noted in the study that the symptoms were “mostly mild to moderate in severity” and that they were less intense when patients had a lower starting dose of 2 mg vs. 4 mg.
A small number of patients (7%) had skin tingling, and there was an increase in heart rate reported for up to 24 weeks in people in the retatrutide group (it went down after 24 weeks).
Retatrutide vs. Ozempic, Wegovy, and other weight loss drugs
Again, research into retatrutide is ongoing. But data so far show that retatrutide may help people lose even more weight than other popular choices.
Previous research on people who took semaglutide (Ozempic, Wegovy) showed that participants lost about 15% of their body weight after six months on the medication. Mounjaro, which is also made by Eli Lilly, has helped study participants lose up to 23% of their body weight.
Beyond Ozempic: Are medications the future of weight loss?
Experts say it’s definitely helpful to have an arsenal of drugs to help people with obesity lose weight. “Different medications have different paths to functioning,” Keatley says. “For example, if someone has a history of kidney issues this medication may not be a good choice, but there may be others on the market that work within those limitations.”
Dr. Shah says more effective medications could alter the way obesity is treated in the future. “This is improving upon what we already have,” he says. “To be able to get weight loss in the 20% range…we’re now seeing medications that can compete with bariatric surgery in terms of weight loss. That’s exciting.”
But Keatley cautions against people thinking that they should go on a weight loss drug if they want to lose a few pounds. “Pharmacological interventions like weight loss drugs are here to stay,” he says. “But these are not drugs like an antibiotic that you take for 10 days and can go back to living life as you were before. These are drugs that will only work long-term with changes in behavior.”
Jessica Cording, R.D., author of The Little Book of Game Changers, expects that a growing number of people who don’t have obesity will want to try these medications. “We’re going to continue to see interest in these kinds of medications,” she says. “The more we learn, the more we’ll come to understand which types of drugs benefit which people the most and get a better understanding of appropriate dosing and regimens.”
Cording notes that research is being done on people with obesity, though—not those looking to drop 5 lbs or so. “Obesity is a medical condition,” she says. “It’s not just having a few extra pounds. But we will always see people wanting to turn to these medications for a quick fix.”
Dr. Shah says that the medications are designed to be used with changes in diet and exercise, too. “Lifestyle changes will still be absolutely the most important things,” he says. “With some of these older medications, if you don’t incorporate diet and exercise, the medications are not as efficacious.”
Keatley points out that the latest study didn’t release data on body composition, and that there are a lot of unknowns on how the medications impact people over time. “Was most of this weight loss fat or was it a combination of water, glycogen, and muscle?” he says. “This is important data for long-term reduction in risk of obesity-related conditions and the data just isn’t there yet.”
As for retatrutide, Dr. Jastreboff says that phase 3 clinical trials will investigate how well people are able to lose weight while taking the medication for longer periods of time.
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