Emily Kwong (2:20)

Today on the show, a new era of weight loss medications. We talk about the science behind the.

Sidney Lupkin (2:25)

Experimental pills and what FDA approval would mean for affordability and access.

Emily Kwong (2:30)

You're listening to Short Wave, the science podcast from npr.

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Emily Kwong (3:52)

Okay Sunny, I want to talk about GLP1s. Am I saying that right? GLP1 GLP1s. How do they work?

Sidney Lupkin (4:00)

So yeah, I talked about this with Andrea Treina. 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.

Emily Kwong (4:17)

So like the magic school bus Ms. Frizzle.

Sidney Lupkin (4:19)

That is correct.

Emily Kwong (4:20)

Our generation science teacher 100%.

Sidney Lupkin (4:23)

Here is her primer on GLP1s and GLP1, by the way, is a hormone your body naturally makes. It stands for glucagon, like pest peptide 1.

Andrea Treina (4:33)

As soon as you ingest food, your body is gonna start secreting GLP1 because it immediately triggers that oh, you've ingested some food and so it's gonna tell your brain you're eating and so it's gonna make sure it triggers that effect so that you start to feel full. But it's very short acting and only lasts a couple of minutes.

Emily Kwong (4:52)

Oh, okay. So in our bodies, the GLP1 hormone does a good job of making you feel satisfied, but only for a short time. How does GLP1 medication work differently?

Sidney Lupkin (5:03)

It much longer. When Novo Nordisk made its medication version of GLP1, the company tweaked it. The active ingredient in both blockbuster drugs, Ozempic and Wegovy is called Semaglutide. Andrea explained how they made it.

Andrea Treina (5:17)

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.

Emily Kwong (5:44)

Oh, okay. So this is why the retooling of the GLP1 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.

Sidney Lupkin (5:55)

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 Rubelsis, which is a semaglutide pill, but it's approved for type 2 diabetes.

Emily Kwong (6:16)

Got it. Okay, 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?

Sidney Lupkin (6:26)

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

Emily Kwong (6:32)

Okay.

Sidney Lupkin (6:33)

The problem is that in your stomach, the drug gets broken down too efficiently and too fast for the semagluti 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.

Andrea Treina (6:49)

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 100 years, we've been trying to make a protein, a peptide based molecule able to be absorbed orally.

Emily Kwong (7:08)

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?

Sidney Lupkin (7:19)

Yeah, they added something to it.

Andrea Treina (7:21)

It is a very long chemical name, but it is abbreviated as snac.

Sidney Lupkin (7:26)

S, N, A, C. Adorable.

Andrea Treina (7:29)

Isn't that cute? Thank 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 snack.

Sidney Lupkin (7:37)

And I love that. And I also love that.

Emily Kwong (7:40)

Okay, how does the snack pill take a ride through your body? Please be my Ms. Frizzle.

Sidney Lupkin (7:45)

I'll let Andrea explain it. But the gist is that this snack 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.

Andrea Treina (7:57)

When you swallow that tablet, it creates a tiny little micro environment 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 your stomach. As soon as this tablet hits the base of your stomach, hits that stomach wall, it creates this little foamy environment directly, directly around the tablet.

Emily Kwong (8:25)

Mmm.

Sidney Lupkin (8:26)

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.

Emily Kwong (8:41)

That's very specific. So this pill might not be for everyone.

Sidney Lupkin (8:47)

Yeah, I definitely heard from people who were, like, past the injection is working for me. I'm good. I don't want this. But others were curious.

Emily Kwong (8:55)

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

Sidney Lupkin (9:00)

So that one is made by Eli Lilly, which makes the injectables Manjaro 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.

Unidentified NPR Staff or Sponsor Voice (9:16)

Yeah.

Sidney Lupkin (9:17)

Eli Lilly is doing a whole new.

Emily Kwong (9:19)

Active ingredient, a whole new compound for their pill formation. Okay, how does it work?

Sidney Lupkin (9:25)

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.

Emily Kwong (9:38)

That seems kind of nice.

Sidney Lupkin (9:39)

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 Lill, who's a senior medical director at the company and worked on studying the new pill.

Dr. Max Denning (9:58)

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 safe and effective medication.

Emily Kwong (10:11)

Okay, so Eli Lilly's putting their pill through clinical trials. Does this guy get to meet the patients?

Sidney Lupkin (10:16)

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.

Dr. Max Denning (10:29)

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, 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?

Sidney Lupkin (11:01)

Ooh, well, does it work also?

Emily Kwong (11:04)

What is this pill called, by the way?

Sidney Lupkin (11:05)

Oh, it's called Orfagliparon. And it did work. According to one study, patients who took Orphaglipron had 12% average weight loss at its highest dose over 72 weeks. And another study showed it it was also effective at lowering patients A1C, which is a measure of blood sugar.

Emily Kwong (11:23)

Okay. How does this pill's efficacy compare to its competitor, the pill made by Novo Nordisk?

Sidney Lupkin (11:27)

Novo Nordisk may have a bit of an edge here. In a study published in September in the New England Journal of medicine, a 25mg semaglutide pill led to a 16, 17% reduction in weight on average over 64 weeks. And that's about the same as WeGovy.

Emily Kwong (11:44)

Oh, so the pill performed about as well as the injectable.

Sidney Lupkin (11:46)

Yeah.

Emily Kwong (11:47)

So, big picture. As a pharmaceuticals person, I know you've talked to many people over the years about GLP1 drugs. What do patients think of this?

Sidney Lupkin (11:55)

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

Emily Kwong (12:01)

Yeah.

Sidney Lupkin (12:01)

But overall, the pill is another option, and that's big, especially when it comes to cost.

Unidentified NPR Staff or Sponsor Voice (12:08)

Yeah.

Emily Kwong (12:08)

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

Sidney Lupkin (12:16)

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.

Emily Kwong (12:25)

Yeah. So are the pills going to be cheaper?

Sidney Lupkin (12:28)

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.

Emily Kwong (12:55)

Wow.

Sidney Lupkin (12:55)

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.

Emily Kwong (13:08)

Sidney Lupkin, thank you so much for joining us.

Sidney Lupkin (13:11)

Thank you for having me.

Emily Kwong (13:17)

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.

Dr. Max Denning (13:34)

Foreign.

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