By Allison Forsyth – Fact checked by Nick Blackmer
- Retatrutide is an investigational weight loss drug that targets three hormones, compared to the one or two targeted by current GLP-1 medications.
- Recent clinical trials suggest retatrutide may deliver even greater weight loss than drugs like Wegovy and Zepbound.
- Experts say the medication is very promising, but it’s still being studied and won’t be available until it completes the FDA approval process.
GLP-1 medications like Ozempic and Wegovy have taken over the weight loss industry. But a new experimental drug from Eli Lilly, called retatrutide, has shown impressive results in recent clinical trials.1 How does it differ from current GLP-1 drugs?
What Is Retatrutide?
Retatrutide, also called “reta” or “triple-G,” is the first triple-hormone receptor agonist. Unlike existing GLP-1 drugs, which primarily target GLP-1 receptors, retatrutide targets three hormones: GLP-1, GIP (glucose-dependent insulinotropic polypeptide), and glucagon.
These hormones help regulate appetite, blood sugar, fat metabolism, and energy expenditure, which may allow retatrutide to produce greater weight loss than GLP-1s, Kevin Gendreau, MD, an obesity medicine physician at Signature Healthcare in Massachusetts, told Health.
The drug, given as a once-weekly injection, is not yet available to patients. FDA approval is expected in 2027 at the earliest, depending on the results of the ongoing phase 3 clinical trials.
How Does It Compare to GLP-1s?
Retatrutide has produced greater weight-loss results in clinical trials than current GLP-1 medications. In the latest study, patients on the highest dose of retatrutide lost an average of 28% of their body weight over 80 weeks, and nearly half lost 30% or more of their body weight.
The average weight loss in clinical trials for the highest dose of Wegovy (semaglutide) was about 15% over 68 weeks; for Zepbound (tirzepatide)—a dual agonist that targets both GLP-1 and GIP—it was about 20% over 72 weeks.
Gendreau said retatrutide’s results are similar to those seen with bariatric surgery, which is still considered the most effective medical weight-loss intervention.8 Patients typically lose about one-third of their body weight within one to two years after surgery and tend to maintain the weight loss long-term.
Eli Lilly is also exploring whether retatrutide can help with conditions like sleep apnea and metabolic dysfunction-associated steatohepatitis (MASH) —which certain GLP-1s are approved to treat. So far, “retatrutide is showing promising benefits well beyond the number on the scale,” Gendreau said.
In the latest trial, the medication improved heart health markers like cholesterol and blood pressure. Retatrutide also led to reductions in knee osteoarthritis pain and liver fat in earlier studies.
It’s too early to determine retatrutide’s tolerability, but its side effects are similar to the gastrointestinal symptoms of GLP-1s. In the latest study, the most commonly reported side effects were nausea, diarrhea, constipation, and vomiting, and the number of reports generally increased with each dose.
“As with any medication in phase 3, we’ll continue to learn more about the long-term safety profile before and after FDA approval,” Janese Laster-Butler, MD, a gastroenterologist, obesity medicine physician, and owner of Gut Theory Total Digestive Care, told Health.
What Experts Want You To Understand About Retatrutide
Experts said retatrutide could significantly expand obesity treatment options. The drug’s potency could allow patients to achieve substantial weight loss at lower doses, which may eventually make retatrutide more affordable than GLP-1s.
According to experts, the new drug may be particularly helpful for people with significant obesity or type 2 diabetes, or with conditions like MASH, osteoarthritis, and sleep apnea. The medication may also work well for people who haven’t been able to lose weight on GLP-1s.
“The patient I picture as the ideal candidate is someone who has already done the work—more protein and fiber, good hydration, fewer processed carbs and refined sugars, consistent resistance training, and who lost weight on a current GLP-1 but has now plateaued,” Gendreau added.
While some patients may be eager to try retatrutide, experts recommended avoiding knockoff versions of the drug and waiting for FDA approval. Compounded or counterfeit retatrutide is illegal in the U.S. and may contain incorrect dosing or undisclosed ingredients.
“Medication should go through the formal FDA process to ensure there are no safety concerns,” Carolynn Francavilla Brown, MD, an obesity expert on the Obesity Medicine Association’s Board of Trustees, told Health.
Laster-Butler also noted that these weight loss drugs are powerful tools—not magic. Like GLP-1s, retatrutide works best when combined with lifestyle changes to help lose fat while maintaining muscle.
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