The longevity bros might be fighting, but that’s not stopping the internet’s early adopters from hyping up the next big thing. Last week, podcast host Andrew Huberman highlighted Retatrutide, a powerful new weight loss drug, posting, “retatrutide is a real challenge to those that liked to bash on other GLP-1 agonists, etc., because it’s used by (soon) everyone.” Retatrutide is “the ultimate good,” said looksmaxxing influencer Braden Peters, a.k.a. Clavicular, in a video on his YouTube channel—before recently revealing that the drug is part of his so-called leanmaxxing stack. Peptides in general are booming, and retatrutide—otherwise known as “reta”—in particular is poised to prove more consequential than even Ozempic in terms of its broader impact on the health system. But what is this drug that “everyone” supposedly is or soon will be using, and why is a 20-something Chad with an affinity for shirtless mirror selfies self-medicating with obesity drugs, anyway?
What is retatrutide?
Ratatrutide is a breakthrough new weight loss drug that is currently showing a lot of promise in its ability to treat obesity and potentially other health conditions. Even at a time when revolutionary new obesity drugs seem to be entering the market every few months, experts that spoke to GQ are framing retatrutide as a major leap forward.
Until now, the most clinically effective obesity drugs on the market have targeted only one or two receptors responsible for managing variables like appetite, blood sugar, and insulin sensitivity. “This one is special and different because it works on three different receptors,” says Jessica Duncan, MD, DABOM, DABA, board-certified obesity medicine physician and Chief Medical Officer at Ivim Health.
You’ve probably heard of semaglutide, the now ubiquitous weight loss medication that belongs to a class of drugs known as glucagon-like peptide-1 agonists, commonly called GLP-1s. These drugs, under common brand names like Ozempic and Wegovy, target the body’s GLP-1 receptors by mimicking natural hormones responsible for regulating appetite and blood sugar levels. They improve insulin sensitivity, help to slow the movement of food through the digestive system, and are ultimately able to increase satiety and reduce food cravings.
Then came tirzepatide, a dual agonist that targets both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. (Popular brands of tirezpatide include Mounjaro and Zepbound.) “They added a second feature, which basically was management of glycogen,” says Erik Nuveen, a triple board-certified surgeon with more than 20 years of experience treating patients with obesity and metabolic disease, and co-founder of Olympus Cosmetic Group. Because of this dual approach, tirzepatide has been shown to more effectively reduce blood sugar levels and ultimately lead to greater weight loss than single-agonist medications like semaglutide.
Enter retatrutide—the triple threat. “This medication adds what's called a glucagon receptor agonist,” Dr. Duncan says. “It works primarily on the liver, in the gastrointestinal tract, and even on the fat tissue. The glucagon effect is really what sets retatrutide apart from other medications, and that's because it has a little bit more of an effect on the liver and the fat tissue.” Basically, retatrutide tackles weight loss through multiple pathways simultaneously. “It’s definitely the most effective means ever created through science to reduce the storage of fat,” says Dr. Nuveen.
Why are you hearing about retatrutide now?
“It's become a hot topic, because the phase three clinical trials are now underway,” Dr. Duncan says. This phase of testing is a big deal for any major drug, as it typically involves larger studies with more patients, which means lots of new data. “Also, it's the next sort of trigger that FDA approval is coming soon,” Dr. Duncan says. “I think people are getting excited about what's to come.”
So, no, everyone is not using Ratatrutide—or at least they shouldn’t be. In fact, right now, nobody except people involved in the clinical trials should be using it at all. “This medication is not FDA approved or on the market yet, so a doctor cannot prescribe this medication to you right now,” Dr. Duncan says. As of this writing, the drug has not received regulatory approval in the US, UK, EU, or anywhere else in the world, for that matter.
“If someone is getting the medication right now, they are not getting it through the normal pathways that we typically think of getting prescriptions through.” Dr. Duncan says. “Suffice to say, people are probably getting it from sources and markets that are not the approved pathways.” It’s not like you have to look very hard. Peptides can be bought online about as easily as anything else. But with few clinical trials to back their efficacy—and safety—or, in this case, the absence of regulatory approval, it’s a veritable wild west.
Why are people getting so excited about yet another obesity drug?
Retatrutide is looking like it might be the most effective weight-loss drug yet, showing greater percentage decreases in total body weight when compared with not only other GLP-1 therapies but even some surgical procedures. “This drug is the most exciting, because it is the most successful,” says Dr. Nuveen. “In clinical trials, its ability to reduce weight is anywhere from 22 to 29 percent, which literally exceeds gastric sleeve surgery. It's better than that.”
“The other thing—and perhaps why it's getting more traction in the wellness space or bio-hacker community—is, even though we're seeing a larger overall total body weight loss, we're not seeing more of a loss of lean muscle mass with this drug. It's sort of on par with other obesity medications,” Dr. Duncan says. The study that she’s referencing—a phase two trial published last year in the journal The Lancet—was done in type-2 diabetics, “but a lot of the literature can be extrapolated to other patient populations,” Dr. Duncan says. “I think that is really what grabbed people and got them excited about it.”
Furthermore, similar to how semaglutide has been found to offer additional health benefits beyond weight loss, such as lowering heart attack risk, and tirzepatide was approved by the FDA for the treatment of sleep apnea, retatrutide is being studied as a potential treatment for other health concerns. “In some of the phase three trials, they're looking at other conditions, like osteoarthritis,” Dr. Duncan says, “and we saw data that showed that this medication had positive effects on metabolic associated liver disease, which we don't really have a treatment for right now. So, this is showing a lot of promise there.”
Should you consider taking retatrutide?
Right now, absolutely not. Trials are ongoing and the drug is not yet approved for use—even if you are able to somehow find it through an unofficial back-channel. “You have to be careful with that—when excitement precedes the proof or evidence and risk profile,” says Dr. Nuveen. “We're just a little bit ahead of the game.”
That said, if and when retatrutide is approved for use, it could be a game changer for people with obesity and, potentially, other health conditions. That’ll be something to discuss with your doctor. “I'm an obesity medicine physician, so I'm always going to tell you that these medications need to be taken under the guidance of a health care provider—for a number of reasons,” Dr. Duncan says.
“The first is that a lot of weight-loss medication requires finding the right dose, and titrating dosage appropriately, and that's something that you always need to do with guidance,” she says. “Of course, these medications come with side effects as well, so you want to partner with somebody who can let you know what the side effects are, what the long-term risks are, and help you to mitigate side effects or deal with them as they arise.”
And if you’re just out here trying to leanmaxx, know that you’re playing with fire. "It's a prescription drug for a reason,” says Dr. Nuveen. “There is that obsessive compulsive component of our society that might dive in and have negative effects.” Nausea, constipation, and extreme low blood pressure are just a few of the risks that Dr. Nuveen warns might be in store for people who don’t actually need this medication, and research is still ongoing.
“It should be used for what it's approved for,” Dr. Duncan says. “If you don't meet that criteria, it's something that you probably shouldn't be using.”