The Weight-Loss Drug Revolution—From Shots to Pills and the Science behind It All
NEWS | 11 January 2026
Kendra Pierre-Louis: For Scientific American’s Science Quickly, I’m Kendra Pierre-Louis, in for Rachel Feltman. Over the past few years GLP-1 drugs have gone from relatively obscure diabetes medications to household names for weight loss. The trend really took off in 2021, when the FDA approved semaglutide for weight loss, sold under the brand names Ozempic and Wegovy. If you’re not taking one, someone in your life likely is. That includes celebrities such as Meghan Trainor and Serena Williams, who say they’ve used GLP-1 injectables. With the rising popularity of these medications, drugmakers are busy creating newer and more potent formulations. This week the first GLP-1 weight-loss pill became available in the U.S.: an oral version of Wegovy. And growing research suggests GLP-1s might have uses beyond diabetes and weight loss, too. On supporting science journalism If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today. But how do these drugs actually work? And do they really stand up to the hype? To get a better understanding of the GLP-1 landscape, we reached out to Bethany Brookshire, a freelance journalist who has extensively covered these medications. Thanks so much for joining us today. Bethany Brookshire: Thank you for having me. Pierre-Louis: I know that you’ve done a lot of work on GLP-1s, and so can you tell us, at a basic level: What is a GLP-1, and then what is a GLP-1 drug? Brookshire: Yeah, GLP-1 is glucagon-like peptide 1. It is produced in the intestine in response to food intake, so, like, when you eat, it is produced. It usually, actually—it circulates in the blood, but it is cut off pretty quick. Pierre-Louis: Mm-hmm. Brookshire: You have an enzyme that usually breaks it down very quickly. And what this does is it increases your insulin secretion; it inhibits another hormone called glucagon. So it slows gastric emptying, it makes you feel full, it increases satiety, and so it changes kind of the way that you feed. So you have two different kinds of feeding: you have homeostatic feeding and [hedonic] feeding. And homeostatic feeding is just, like, you are starving ... Pierre-Louis: Mm-hmm. Brookshire: And you’re gonna eat, and, like, this thing in front of you isn’t great, but you’re hungry, and there you go. That is homeostatic feeding, and you’ll eat enough of it, but you’re not gonna go crazy. Whereas [hedonic] feeding is like, “I really enjoy—we are recording during the holidays, and I really enjoy the taste of cheese ...” Pierre-Louis: [Laughs.] Brookshire: “And I would like to be full of a lot of cheese,” and you eat a lot of cheese, and you eat cheese even when you shouldn’t eat cheese because it’s great. That is [hedonic] feeding. [Laughs.] Or you do it for emotional reasons—there’s lots of reasons ... Pierre-Louis: Right. Brookshire: People might overeat. And GLP-1, the hormone, prevents that kind of thing. It promotes satiety and says, “Okay, you’re cut off. You had enough.” Pierre-Louis: And to be clear, this is, like, naturally produced—like, our body naturally produces ... Brookshire: Yes. Pierre-Louis: This hormone. Brookshire: Yes, so your body naturally produces GLP-1, and GLP-1 activates GLP-1 receptors, which is how it produces its effects. So these GLP-1 receptors are all over the body. They are all over the brain. They are constantly doing things. And so you have these receptors, and where you have receptors you can create drugs to activate those receptors. And so the drugs that are mimicking GLP-1 are called GLP-1 receptor agonists. And when we say “agonist” in pharmacology what we mean is that it turns on the receptor, so it’s mimicking your normal GLP-1, right? If it were blocking it, we’d call it an antagonist. But these are all agonists, so they are stimulating that receptor. They are saying, “Go, go, go.” And so GLP-1 receptor agonists is what they’re called in the literature, but of course, in public discourse we’ve just started calling them GLP-1s. And these are the drugs like semaglutide, liraglutide, exenatide, tirzepatide—the “-atides” [Laughs] because pharma loves to name things. These are activators of these receptors. They’re just acting like GLP-1, much harder [Laughs] and much longer than your endogenous GLP-1 would. Pierre-Louis: So normally, the GLP-1 that our body produces, it gets produced after we eat something, it hangs around for a relatively short period of time, and it goes away ... Brookshire: Mm-hmm, yes. Pierre-Louis: But when we take these GLP-1 agonists, these drugs, it kind of lingers in our system for a lot longer, sort of creating a bigger sense of satiety than we would naturally. Brookshire: Yes, they linger a lot longer. I mean, lord knows with the injectables you take them once a week—they linger a really long time. Pierre-Louis: Mm-hmm. Brookshire: And they’re also at much higher doses, so they’re hammering that receptor much harder than the natural GLP-1 that you might produce. Pierre-Louis: And originally—these drugs have been around for a while. But originally, they were mostly for diabetes, is my understanding. Brookshire: Yes, the first GLP-1 receptor agonists were approved for diabetes, and that’s partially because they increase insulin secretion, which is very important if you have type 2 diabetes and you are less sensitive to insulin or you don’t produce enough insulin; it inhibits glucagon, so it slows your gastric emptying. The effects of GLP-1 receptor agonists on blood sugar levels and on insulin are unparalleled. They are incredible drugs for diabetes, and they’ve been a real game changer in type 2 diabetes treatment. They’re really great for that. Pierre-Louis: And then they’ve sort of risen to this public consciousness because as they were used for type 2 diabetes we became aware of kind of, like, a side effect, which is it helps some people lose weight. Brookshire: Yes, it helps a lot of people lose weight. And yeah, the doses that are used for type 2 diabetes management in particular ... Pierre-Louis: Mm-hmm. Brookshire: Do not cause as much weight loss; they’re lower doses. So people—when they started noticing that some people were losing weight on these drugs the pharmaceutical companies were like, “Hmm, sniff, sniff, I smell money,” and started kind of working with higher doses of the drugs to produce more weight loss, and so you see much higher doses. For example, Ozempic is for diabetes, and Wegovy is for weight loss. They are both the same drug—they’re both semaglutide—but semaglutide in Wegovy is much higher. So there’s higher doses that are required to produce the weight loss. Pierre-Louis: And because of that weight-loss benefit, if you will, we now have way more people on these drugs. Like, how many people nationwide are on a GLP-1 at any given time? Brookshire: You know, it’s hard to find the numbers. I see some numbers saying that one in eight Americans ... Pierre-Louis: Mm-hmm. Brookshire: Have taken GLP-1s. And keep in mind, of course, not everybody is on them for a long period of time. There are a lot of people who quit them ... Pierre-Louis: Mm-hmm. Brookshire: For various reasons: either they’ve lost the weight they want; maybe it’s not working as well as they want; the side effects are intolerable, which they really can be. But I’ve seen one in eight Americans have been on them. We know, in 2024, [about] a quarter of people with type 2 diabetes were on GLP-1s, so—obviously, people taking them for type 2 diabetes are different from people just taking them for weight loss. And I also was seeing numbers saying, “Well, you know, one out of every five kids—“is now technically ‘obese’”—I put that in air quotes—and so therefore, they could be eligible to take these drugs. Pierre-Louis: That’s a lot of people. Brookshire: It is a lot of people. Pierre-Louis: And I wanna talk a little bit more about what that means in terms of newer drugs coming out and successes and side effects. But before we go down that path, one of the other things that has come out is that GLP-1s do seem to have other knock-on effects beyond weight loss and beyond diabetes, and so can you talk a little bit about some of the potential of GLP-1s for other health conditions? Brookshire: Right now GLP-1s are very much in their “What can’t it do?” phase. And the thing is then you find out what it can’t do, and there are many things these drugs cannot do. We do know that they can help a lot with cardiovascular problems. So people who have, you know, kind of long-term cardiovascular difficulties, these drugs can really help with that. They really help with metabolic dysfunction; as we’ve said, like, for insulin they are a game changer. We’ve seen some interesting effects on things like inflammation. Pierre-Louis: Mm-hmm. Brookshire: So people who suffer a kind of long-term chronic inflammation can have some positive effects. As we mentioned it is active in the brain, and it controls—it helps kind of nudge different kind of chemical messengers in the brain ... Pierre-Louis: Mm-hmm. Brookshire: Including serotonin and including dopamine. And so there’s some really important evidence that it could really help people who are struggling with things like alcoholism because it makes drugs and it makes alcohol much less appealing, which is—I mean, that’s great; this is an incredibly difficult disorder. It has also been looked at for things like Alzheimer’s, which it had way less success. There was, like, a small effect, and it doesn’t appear to have worked out. It does appear to help things like, potentially, joint pain ... Pierre-Louis: Mm-hmm. Brookshire: And of course, that could be because it has some positive effects on inflammation. It could also be because for people who are in very large bodies, you know, joints can be really difficult, and so taking off some of that weight can help with joints. So yes, there are a lot of different kind of knock-on effects here. There’s some really interesting and compelling research showing it may help some of the effects of polycystic ovarian syndrome ... Pierre-Louis: Mm-hmm. Brookshire: Which is a really nasty and far more common disorder than people realize. Pierre-Louis: Yeah. Brookshire: And it could potentially, in some cases, help with fertility, either with helping people reach weight cutoffs so that they can be approved for fertility treatment or in that they could help kind of restore or improve fertility in people for whom—if, if they are in larger bodies and have metabolic dysfunction, improving metabolic function can sometimes help with fertility. So there, there’s a bunch of potential impacts that are really positive and could really, really help some people. Pierre-Louis: That’s really promising and interesting, and because we’re kind of in this heady moment of people being really awed by these drugs, it seems like more and more of them are coming out. I know that for the first time the FDA approved an oral GLP-1 specifically for weight loss. Can you talk a bit about this new pill and also sort of what we’re seeing in kind of the GLP-1 pipeline? Brookshire: There’s so much. So semaglutide—that is your Ozempic; that is your Wegovy. That is from Novo Nordisk. It was approved just before Christmas, December 22. There have been some challenges with developing these drugs as a pill. They are mostly injectable right now, and people don’t like taking needles. [Laughs.] Nobody wants it. So you know that if they’re releasing something as a needle, it is because it’s really hard ... Pierre-Louis: Yeah. Brookshire: To get it to do anything else. And in this case it’s a bioavailability issue. So basically, this is a gastrointestinal hormone that GLP-1 receptor agonists are mimicking, right? Pierre-Louis: Mm-hmm. Brookshire: Things in the gastrointestinal tract get broken down really, really fast, and so ... Pierre-Louis: Yep. Brookshire: When you’re taking something orally, as a pill, like, very little of that is gonna make it into your bloodstream, and so that’s been a real challenge. So for example, the effective dose of semaglutide for weight loss is 2.4 milligrams injected. Pierre-Louis: Mm-hmm. Brookshire: As a pill it is 25 milligrams, so they really had to go up. And one of the major side effects is gastrointestinal upset: nausea, constipation, really nasty vomiting ... Pierre-Louis: Mm-hmm. Brookshire: It’s very upsetting. Heartburn. There’s a—sulfurous burps is a big one ... Pierre-Louis: That is a very descriptive term. Brookshire: Sorry. [Laughs.] Pierre-Louis: [Laughs.] Brookshire: It’s true! [Laughs.] Anyway, so the side effects can be very uncomfortable. And then if you’re taking a pill, you are taking the thing causing those side effects and you are dropping it right into the stomach. [Laughs.] Pierre-Louis: Yeah. Brookshire: The side effects have been really hard to combat. Pierre-Louis: Mm-hmm. Brookshire: You’re not getting rid of those anytime soon, I can tell you. But Novo Nordisk has finally done it, and they’ve shown the pill has [a] 16.6 mean weight loss percentage over 64 weeks, so that’s about even with the injectable. But they’re not the only ones because Eli Lilly will never be outdone by Novo Nordisk. This is a pharma arms race, like, of which the world has never seen. And they are trying an oral drug called orforglipron. Pierre-Louis: [Laughs.] That is a mouthful. Brookshire: [Laughs.] It is a GLP-1 receptor agonist. It’s an oral drug. It’s supposed to be cheaper. The gastrointestinal side effects, again, seem to be pretty bad. And you also have to remember: there is another drug called Rybelsus. Rybelsus already exists. It is already approved. It is an oral GLP-1. Pierre-Louis: Mm-hmm. Brookshire: It is approved for type 2 diabetes. The Rybelsus and the oral semaglutide both of them have real restrictions around how they have to be taken. So you have to take them first thing in the morning ... Pierre-Louis: Mm-hmm. Brookshire: You can take them with no more than four ounces of water, and then you must eat or drink nothing for 30 minutes. It’s gonna be a burden, but I also—if I were a betting person, I mean, a pill’s gonna be way more popular ... Pierre-Louis: Yeah. Brookshire: Than having to take an injectable that needs to be kept in the fridge and, you know, is hard to get. So yeah, those are all on the way. There are also new injectables ... Pierre-Louis: Mm-hmm. Brookshire: That are on the way as well. Pierre-Louis: And those are? Brookshire: So there are two big ones that I’m seeing coming out. The biggest one that I’m already seeing people take—if you hunt it down on, like, social media, TikTok in particular, you can find people already getting this drug from compounding pharmacies. It is, I believe, pronounced “RET-ah-TRU-tide.” Pierre-Louis: Mm-hmm. Brookshire: I wanna call it “re-TAH-tru-TIDE.” And so people call it reta, for obvious reasons. [Laughs.] And reta, big phase 2 results came out for that in 2023. It’s an Eli Lilly drug. I am seeing 24 percent weight loss or even higher, up to a third of body weight ... Pierre-Louis: Oh, wow. Brookshire: In 48 weeks. Pierre-Louis: That is an incredible amount of weight. Brookshire: It’s a lot. And then there’s another one that is ... Pierre-Louis: Mm-hmm. Brookshire: Novo Nordisk. Novo Nordisk is really interested in this drug called CagriSema. And so CagriSema is actually not one drug that does several things; it is two drugs that each do one thing. And in this case it’s a combination drug, and if people are fully adherent, [roughly] 40 percent of patients lost a quarter [or more] of their body weight. And again, they filed for FDA approval for CagriSema on December 18. So, I mean, pharmaceutical companies know where the money is. Pierre-Louis: You raised something interesting, I think, when you were talking about how if you know a compounding pharmacist, you can get reta—or some people are accessing it. Can we talk a little bit about this, like, gray market of GLP-1s? Which is wild to me because you are talking about injecting something into your body that may not have the oversight that you’re expecting. Brookshire: Yeah, so compounding pharmacies play an interesting role in the U.S. drug system. Compounding pharmacies can be a real lifeline when people can’t get specific drugs ... Pierre-Louis: Mm-hmm. Brookshire: That they desperately need. So for example, I know for a lot of people with major skin conditions—and that includes me; I rely on compounding pharmacies to compound the topical steroids that basically hold my skin together. [Laughs.] So, you know, compounding pharmacies are really important for that sort of thing. When the GLP-1s first kind of really came to public attention, 2022, 2023, for weight loss there was a real shortage ... Pierre-Louis: Mm-hmm. Brookshire: Of the drugs. Novo Nordisk in particular just could not keep up with demand. Like, the entire country of Denmark was producing these drugs. [Laughs.] And so the federal government said, “Okay, compounding pharmacies can make these drugs ...” Pierre-Louis: Yep. Brookshire: “For this period of time,” and you can do it for cheaper because they are often cheaper. And so people started getting access to them via these compounding pharmacies. And I think that also has led a lot of people to kind of trust these pharmacies, right? Pierre-Louis: Mm-hmm. Brookshire: Many of them have been injecting these drugs from these pharmacies for years now. Pierre-Louis: Yep. Brookshire: Right? Why wouldn’t they trust it? And to be clear compounding pharmacies are not inherently untrustworthy outfits. But they are not subject to the same scrutiny. They’re kind of making small-batch versions ... Pierre-Louis: Mm-hmm. Brookshire: Of these drugs. And of course, they’re not necessarily dosed or formulated. So when you get the major drugs, the major GLP-1 agonists, from the companies you get them in these little dosing pens. They’re already, like, measured out and everything. When you get them from a compounding pharmacy you get a vial and a needle and some hope. And so people have to measure it out themselves, and this can be just fine. Pierre-Louis: Mm-hmm. Brookshire: It can also introduce human error, and it can also allow people to misuse them. People who have histories of eating disorders ... Pierre-Louis: Mm-hmm. Brookshire: Find these drugs extraordinarily compelling. For people with anorexia, people with bulimia, drugs like these—you know, there is nothing that you want more than to completely kill your appetite. [Laughs.] And so they’re really compelling, and I’ve seen case reports of people who have been hospitalized because they have, you know, been taking more than they should. They’ve been taking it without a prescription. They’ve been obtaining it quasi-legally at best. Pierre-Louis: Right. Brookshire: So that does happen. There are also just some overall kind of downsides ... Pierre-Louis: Mm-hmm. Brookshire: To these drugs, right? Like, we’ve talked about the side effects. I mentioned that GLP-1 receptors are all over the brain. One of the places they are in the brain is in this area of the brain called the area postrema, which sounds like some sort of bizarre mixed martial art but is actually a brain area responsible for vomiting. [Laughs.] Pierre-Louis: Oh. [Laughs.] Brookshire: Yeah. [Laughs.] So, you know, as long as you have these drugs hitting those receptors you’re gonna have those gastrointestinal side effects. It’s gonna be bad. We know that overactivation of GLP-1 receptors ... Pierre-Louis: Mm-hmm. Brookshire: So really high doses ... Pierre-Louis: Mm-hmm. Brookshire: Can also have psychiatric side effects. It can cause depression. It can cause apathy, anxiety. And this is not super surprising when you think about it. You know, a lot of the symptoms of depression and apathy in particular is a feeling called anhedonia ... Pierre-Louis: Yep. Brookshire: Which is basically unable to take pleasure in things, and GLP-1s make food lose pleasure. They make food fuel, and many people think they want this. But maybe you don’t [Laughs], right? That can be really difficult. We talked about anorexia and bulimia, but there’s also—people are interested in using GLP-1s for binge-eating disorder ... Pierre-Louis: Mm-hmm. Brookshire: Which is the most common of the eating disorders. And while it can really help with people bingeing it doesn’t necessarily address the underlying disorder, so, like, it doesn’t address why someone is bingeing, right? Pierre-Louis: Right. Brookshire: And so that’s something that people who treat eating disorders are concerned about with these drugs. More practically speaking, some of the higher-dose drugs, so tirzepatide ... Pierre-Louis: Mm-hmm. Brookshire: Tirzepatide can decrease the efficacy of oral birth control because it causes the drugs to stay in your stomach longer ’cause it makes everything stay in your stomach longer—it delays gastric emptying. You may have heard the term “Ozempic babies.” Ozempic babies are not actually a real thing. It’s more that very rapid weight loss can cause recalibration of menstrual cycling in some people. And so you will see this with rapid weight loss from GLP-1s, though you’ll also see it with rapid weight loss from bariatric surgery; people have pregnancies after bariatric surgery for similar reasons. Another downside is the drugs are super expensive ... Pierre-Louis: Yeah. Brookshire: And we know this. People don’t necessarily wanna be on them forever ... Pierre-Louis: Mm-hmm. Brookshire: Right? And this is a chemical diet, basically. It’s a chemical diet that you are putting your body and your brain on. And when your body and brain is not on that diet people regain the weight. They’re going to regain it; they may gain even more. We also know that the very extreme, rapid weight loss can cause very difficult effects on the liver and the gallbladder in particular. And this is not specific, again, to the GLP-1s—it’s the weight loss. And so you get people who have to get their gallbladders out a lot or suffer pretty bad gallstones, liver problems, things like that. All of those are kind of the side effects of the rapid weight loss. And, you know, weight loss itself, it’s something that is very important to a lot of people because our society is very cruel to people in larger bodies for many, many reasons. And so it’s utterly reasonable that you’d want all the benefits of these drugs, but it’s not a silver bullet, right, ’cause nothing is. Pierre-Louis: That’s our show. Don’t forget to tune in on Monday, when we’ll give you a rundown on what’s been happening in science news. Science Quickly is produced by me, Kendra Pierre-Louis, along with Fonda Mwangi, Sushmita Pathak and Jeff DelViscio. This episode was edited by Alex Sugiura. Shayna Posses and Aaron Shattuck fact-check our show. Our theme music was composed by Dominic Smith. Subscribe to Scientific American for more up-to-date and in-depth science news. For Scientific American, this is Kendra Pierre-Louis. See you next time!
Author: Alex Sugiura. Kendra Pierre-Louis. Sushmita Pathak.
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