GLP-1 pills are on the way. Here’s what to know : Short Wave : NPR

SPEAKER 1: You’re listening to Short Wave from NPR.

EMILY KWONG: Hey, Short Wavers. I am here with NPR pharmaceuticals correspondent Sydney Lupkin today to talk about something that has really changed the game when it comes to weight loss, which is injections. When did this all start?

SYDNEY LUPKIN: I mean, it all started with celebrity weight loss.

REPORTER 1: One hot topic everyone in Hollywood still seems to be talking about is Ozempic.

REPORTER 2: You’re on Ozempic or one of those things.

REPORTER 3: Or Wegovy or whatever.

REPORTER 2: Yeah, or you get work done. Like, just stop.

LUPKIN: Then, it wasn’t a secret anymore.

KWONG: Yeah, I remember even Serena Williams came forward as, like, a spokesperson for the telehealth company Ro’s GLP-1 injections.

SERENA WILLIAMS: I knew my body was missing something it needed. For me, the answer was GLP-1.

LUPKIN: Now these weight loss injections, called GLP-1s, are kind of everywhere. Examples include Ozempic, which is kind of the Kleenex of GLP-1 drugs, but is actually officially for type-2 diabetes, and Wegovy. These are drugs you inject under the skin once a week. And these injectable drugs have become a valuable tool for millions of people trying to get to a healthier weight. We’re talking people who’ve never been able to lose weight and keep it off, finally finding something that works for them.

KWONG: These are clearly life-changing medications, and also, it seems a big commitment. I mean, not everyone is going to want to inject something weekly for weight loss.

LUPKIN: For sure. And they’re not for everyone or for every wallet. Injectables do have a sticker price of over $1,000 a month. And insurance coverage has been tricky to navigate for a lot of people. So there’s a lot of excitement around a new pill form of the drug.

LUPKIN: We’re going to talk about two types of these pills. The first is a Wegovy pill that’s expected to win FDA approval by the end of the year. And then there’s another kind of obesity pill that could right behind it.

KWONG: Today on the show, a new era of weight-loss medications. We talk about the science behind the experimental pills.

LUPKIN: And what FDA approval would mean for affordability and access.

KWONG: You’re listening to Short Wave, the science podcast from NPR.

KWONG: OK, Sydney, I want to talk about GLP-1s. Am I saying that right?

LUPKIN: GLP-1.

KWONG: GLP-1s. How do they work?

LUPKIN: So yeah. I talked about this with Andrea Traina. Her background is in clinical pharmacy, and now she’s an obesity director at Novo Nordisk. That’s the company that makes Ozempic and Wegovy. And Emily, at my request, she went full Frizzle during our interview.

KWONG: So like The Magic School Bus, Ms. Frizzle.

LUPKIN: That is correct.

KWONG: Our generation’s science teacher.

LUPKIN: 100%. Here is her primer on GLP-1s. And GLP-1, by the way, is a hormone your body naturally makes. It stands for glucagon-like peptide 1.

ANDREA TRAINA: As soon as you ingest food, your body is going to start secreting GLP-1 because it immediately triggers that, oh, you’ve ingested some food. And so it’s going to tell brain you’re eating. And so it’s going to make sure it triggers that effect so that you start to feel full. But it’s very short acting. And it only lasts a couple of minutes.

KWONG: Oh, OK. So in our bodies, the GLP-1 hormone does a good job of making you feel satisfied, but only for a short time. How does GLP-1 medication work differently?

LUPKIN: It lasts much longer. When Novo Nordisk made its medication version of GLP-1, the company tweaked it. The active ingredient in both blockbuster drugs, Ozempic and Wegovy, is called semaglutide. Andrea explained how they made it.

TRAINA: We took out a couple of amino acids and exchanged them for other ones so that the molecule can’t immediately be degraded by the enzyme that our body naturally makes to break it down. And then the second thing we did is we added a big fatty acid chain to the end of it so that it binds to protein and hangs out in the body for longer. So semaglutide actually has a half life of a week instead of just two minutes.

KWONG: Oh, OK. So this is why the retooling of the GLP-1 hormone is why Ozempic and similar injectables are taken weekly, because the chemical at the core of it all, semaglutide, has a half life of a week.

LUPKIN: Right. By the way, there are four different blockbuster injectables. Ozempic and Mounjaro are for type-2 diabetes. And Wegovy and Zepbound are for obesity. But the latest twist is that now there’s a possibility of a pill– two pills actually. And to be clear, we’re not talking about Rybelsus, which is a semaglutide pill, but it’s approved for type-2 diabetes.

KWONG: Got it. OK, these are two new pills, folks. A semaglutide you can swallow, and another different pill, which is a new compound. Which pill do you want to talk about first?

LUPKIN: Let’s talk about the pill made by Novo Nordisk, whose active ingredient is semaglutide. It’s a peptide, a protein.

KWONG: OK.

LUPKIN: The problem is that in your stomach, the drug gets broken down too efficiently, and too fast for the semaglutide to get into the bloodstream and do its job all over your body. Andrea says to think about how your stomach breaks down some chicken that you’ve eaten.

TRAINA: Our body is trained to release enzymes, and to attack those proteins almost immediately to break them down into smaller pieces so that they can be absorbed. So for a hundred years, we’ve been trying to make a protein, a peptide-based molecule able to be absorbed orally.

KWONG: This sounds like a tricky design problem. So how did the scientists at Novo Nordisk get around this and make that peptide-based molecule that our bodies wouldn’t immediately want to break down?

LUPKIN: Yeah, they added something to it.

TRAINA: It is a very long chemical name, but it is abbreviated as SNAC. S-N-A-C.

LUPKIN: Adorable.

TRAINA: Isn’t that cute? [LAUGHTER] Oh my goodness. No pun intended, but it is just the first letter from each of the chemicals within the structure. And it just worked out to be SNAC, and I love that.

LUPKIN: And I also love that.

KWONG: OK, how does the snack pill take a ride through body? Please be my Ms. Frizzle.

LUPKIN: I’ll let Andrea explain it, but the gist is that this SNAC thing creates a little protective buffer zone around the pill to keep it from getting broken down too quickly and help it get absorbed into the bloodstream.

TRAINA: When you swallow that tablet, it creates a tiny little microenvironment at the base of the stomach right where that tablet sits. And so it’s kind of, if you think about dropping an Alka-Seltzer tablet in a glass of water, that immediate fizzy reaction that occurs, that is what happens in stomach as soon as this tablet hits the base of your stomach, hits that stomach wall. It creates this little foamy environment directly around the tablet.

LUPKIN: Then it can do all those other things to make you feel full and regulate blood sugar. The catch is that you have to take this pill on an empty stomach and wait 30 minutes before eating anything else for it to work.

KWONG: That’s very specific. So this pill might not be for everyone.

LUPKIN: Yeah, I definitely heard from people who were like, pass. The injection is working for me. I’m good. I don’t want this. But others were curious.

KWONG: Now earlier you had mentioned there was another pill that might come onto the scene. Who is making that one?

LUPKIN: So that one is made by Eli Lilly, which makes the injectables Mounjaro and Zepbound. And they both share the same active ingredient called tirzepatide. But unlike Novo Nordisk, which took its injectable active ingredient and made it in pill form with some tweaks, Eli Lilly is doing a whole new active ingredient.

KWONG: A whole new compound for their pill formation. OK, how does it work?

LUPKIN: Eli Lilly isn’t saying in detail yet, but I can tell you this. It is not a peptide, so it doesn’t have the same restrictions around when you need to take it. You don’t have to take it on an empty stomach and wait half an hour before eating anything.

KWONG: That seems kind of nice.

LUPKIN: Yeah, but its approval is probably a little ways behind the Novo Nordisk pill. And maybe here is a good place to spell out just how long the development and approval process for these drugs can be. I talked to Dr. Max Denning at Eli Lilly, who’s a senior medical director at the company and worked on studying the new pill.

MAX DENNING: You need a huge number of doctors, you need a huge number of sites to be participating in the clinical trials to get all of that data and make sure that this is a safe and effective medication.

KWONG: OK, so Eli Lilly is putting their pill through clinical trials. Does this guy get to meet the patients?

LUPKIN: Actually, never. His job was to design and oversee clinical trials for the pill and then step back. The trials are double blind, meaning that neither the patient nor the doctors know who got the drug and who got the placebo.

DENNING: So you design these trials, you spend maybe six months doing that, you start them up, and then you run the trial. And that process of finding all of the participants that come for all of their visits, take the investigational medicine as prescribed, and then get to the end of the study, that whole process takes maybe two, two and a half years. And for me, the anticipation coming up to that first moment when the data card flips over and you see, does this medicine work?

KWONG: Ooh. Well, does it work? Also, what is this pill called, by the way?

LUPKIN: Oh, it’s called orfoglipron. And it did work. According to one study, patients who took orfoglipron had 12% average weight loss at its highest dose over 72 weeks.

KWONG: Cool.

LUPKIN: And another study showed it was also effective at lowering patients’ A1C, which is a measure of blood sugar.

KWONG: OK, how does this pill’s efficacy compare to its competitor, the pill made by Novo Nordisk?

LUPKIN: Novo Nordisk may have a bit of an edge here. In a study published in September in the New England Journal of Medicine, a 25-milligram semaglutide pill led to a 16, 17% reduction in weight on average over 64 weeks. And that’s about the same as Wegovy.

KWONG: Oh, so the pill performed about as well as the injectable?

LUPKIN: Yeah.

KWONG: So big picture, as a pharmaceuticals person, I know you’ve talked to many people over the years about GLP-1 drugs. What do patients think of this?

LUPKIN: Some just aren’t into the idea. They’re like, hey, the injections work for me. Why would I switch?

KWONG: Yeah.

LUPKIN: But overall, the pill is another option. And that’s big, especially when comes to cost.

KWONG: Yeah, you said earlier that injectables can be over $1,000 a month, certainly a few hundred dollars a month depending on your situation.

LUPKIN: And that’s on top of already-high insurance premiums. So even if you have insurance coverage, it might be really limited or still require a big out-of-pocket payment.

KWONG: Yeah. So are the pills going to be cheaper?

LUPKIN: So we don’t officially know what the sticker price for the pills is going to be yet. Novo Nordisk has not said, Eli Lilly has not said. But generally, pills are easier to manufacture. Therefore, they’re cheaper to manufacture, which could result in a downstream lower price. We also know that there have been deals with the Trump administration announced earlier this year to sell the pills to consumers, not using their health insurance for $149 a month.

KWONG: Wow.

LUPKIN: Now that is not a sticker price, but it could mean that a lower sticker price is coming. And that could mean better insurance coverage, more access, basically just more people able to get their hands on these if they need them.

KWONG: Sydney Lupkin, thank you so much for joining us.

LUPKIN: Thank you for having me.

KWONG: This episode was produced by Rachel Carlson and edited by Brent Baughman. Tyler Jones checked the facts. The audio engineer was Kwesi Lee. Beth Donovan is our vice president of podcasting. I’m Emily Kwong. Thank you for listening to Short Wave from NPR.

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