Originally published on WomansWorld.com by Allison Nemetz on December 17, 2025. Reviewed by Dr. Daniel Ghiyam, MD.
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Ozempic and Zepbound, you’ve got company. Eli Lilly just dropped jaw-dropping results from the final phases of testing for retatrutide (nicknamed “Reta”), a brand new GLP-1 weight loss drug that should soon be submitted to the FDA for approval. The average participant getting a 12-mg weekly injection lost 71 pounds in 68 weeks.
“This is beyond what we see with any other medication on the market, and it is what we see with some bariatric surgeries,” obesity medicine expert Jennah Siwak, MD, reported to her hundreds of thousands of followers on TikTok. “This is insane.”
While it’s important to note that the study still needs to be finalized and reviewed before any of this is official, it’s okay to get excited. And not just because of the significant weight loss. What other amazing things does the drug promise to do? And, among retatrutide side effects, what’s the surprising reason some people dropped out of the clinical trial? Hint: Many of us might see it as a benefit. Keep reading for everything you’ll want to know.
What is Retatrutide and Why is it Called “Triple G”?
Retatrutide is a new entry in the class of GLP-1 agonist drugs, which mimic an anti-diabetes/anti-obesity hormone called GLP-1 and keep levels up to 1,000 times higher than normal. Earlier versions including Ozempic, Wegovy and the generic semaglutide only act on GLP-1. Meanwhile, Mounjaro, Zepbound and the generic tirzepatide elevate both GLP-1 and a second anti-diabetes/anti-obesity hormone called GIP.
“Reta” (which has no official brand name yet) does everything its predecessors can do, plus it boosts glucagon, a hormone that stimulates fat metabolism. Because it amps up GLP-1, GIP and glucagon, “it’s referred to as the ‘Triple G,'” shared Dr. Siwak. It sounds a lot more powerful, and there’s a good chance it is. Head-to-head comparison studies are needed, but the Triple G weight loss drug may be the best GLP-1 for weight loss and much more.
Retatrutide May Ease Knee Pain Too
Eli Lilly’s latest retatrutide phase 3 clinical trial results are from a study called TRIUMPH-4, which was done on people with a BMI of 35 or higher (that’s at least 204 pounds for a 5’4 woman). What sets TRIUMPH-4 apart from early testing on drugs like Ozempic, Wegovy, Mounjaro and Zepbound is that participants were diabetes-free. Instead, they all had significant knee osteoarthritis.
“The standout finding is not just the magnitude of weight loss, but the concurrent improvement in knee osteoarthritis pain and function,” says Daniel Ghiyam MD, a California-based physician specializing in hormone optimization, metabolic health and preventive care. Even on the lower dose of retatrutide, knee pain was reduced by an average of 74 to 75 percent, with more than one in eight becoming completely pain free. Mobility and physical function of the knee also improved 72 to 74 percent.
“Most osteoarthritis treatments such as NSAIDs, steroid injections or physical therapy focus on symptom control rather than underlying mechanical drivers,” says Dr. Ghiyam. Retatrutide appears to target pain in other ways. That includes reducing excess weight, of course. But GLP-1s have also demonstrated impressive anti-inflammatory effects, notes Ashley Koff, RD, author of Your Best Shot: The Personalized System for Optimal Weight Health — GLP-1 Shot or Not. Plus, she says the hormones stimulated by retatrutide may help optimize bone health.
Could “Reta” Lead to Fewer Knee Replacements in the Long Term?
The new findings certainly offer hope. “This is huge because knee arthritis is one of the most frustrating things as a patient to deal with. There are just not that many treatments, and a lot of people really don’t want to have surgery,” said Dr. Siwak. In other words, not only might the drug get results like gastric bypass, it could substantially delay or (for people with less advanced arthritis) possibly even eliminate the need for pricey and painful knee replacement.
Will this link to knee issues make insurance more likely to approve GLP-1 meds for those of us who don’t have diabetes? Only time will tell, but it’s a big reason more GLP-1 studies are being conducted on nondiabetics, says Dr. Ghiyam.
Proof the GLP-1 Helps Unclog a Fatty Liver
An estimated 70 percent of us (about 180 million American adults) have fatty buildup clogging our livers, usually “residue” that gets stuck in the organ as mass amounts of ultra-processed food pass through. Retatrutide shows promising results in treating this. “No one is talking about how impressive the liver fat loss is, but it’s huge,” notes Koff. In fact, during phase 2 testing of the drug, liver fat dropped 43 percent with a lower dose and up to 82 percent with the higher dose in just 24 weeks.
As liver fat is reduced, the liver can do its hundreds of jobs better. Liver fat reductions with retatrutide were associated with reduced abdominal fat, improved blood sugar and insulin function and better cholesterol. Unclogging the liver can also lead to benefits ranging from less fatigue and brain fog to reduced risk of heart attack and cancer. The healthier the liver, the better our overall wellbeing tends to be.
Retatrutide Side Effects Patients Experienced
Like any drug, retatrutide comes with risks and isn’t right for everyone, cautions Koff. The most common side effects were nausea, diarrhea, constipation and vomiting, about on par with other GLP-1 meds. And since “Reta” acts on GLP-1 levels in the same way as the older meds, it likely has all the side effects of earlier GLP-1 meds, such as the possibility of worsening diabetic retinopathy and rare instances of pancreatitis.
What side effects were different with retatrutide? “Twenty percent of people taking the 12 mg dose experienced dysesthesia, which is an altered sense of touch,” according to Dr. Siwak. “Something that normally wouldn’t feel unpleasant feels unpleasant, maybe burning or painful.”
Dr. Siwak adds that we still need to hear more about heart arrhythmias, a possible issue detected in earlier clinical trials. Some smaller analyses of data indicate mild to moderate cardiac arrhythmias occurred in four to 14 percent of retatrutide-treated subjects.
Excessive Weight Loss is a Reported Side Effect of Retatrutide
Here’s the biggest surprise: Nearly one out of every five people on the 12-mg dose of retatrutide didn’t complete the study, a fairly high dropout rate. “One of the main reasons for discontinuation was perceived excessive weight loss,” per Dr. Siwak. “So people had decided they had lost enough or too much and they were done.” Basically, if weight loss is your main health goal, you may find retatrutide works a little too well, and a less powerful drug or lifestyle changes may be better for you.
When Will Retatrutide Be Available?
Once Eli Lilly submits the drug to the FDA (which could happen before the end of the year), a standard review of efficacy and safety takes 10 to 12 months. But if it’s determined this drug represents a significant advancement, it could be upgraded to a priority review, which takes about six months. We reached out to Eli Lilly about the likely cost of retatrutide, but they say pricing has yet to be set.