Medicine: The Problems And Possibilities Of Peptides

0:00This week on Shortwave, you are what you eat may not be a phrase you associate with your mental health, but... One in three people have insulin resistance in our country. And if you have insulin resistance, you are double the likelihood of developing major depression. We explore the link between your body and your brain. Listen on Shortwave, the science podcast from NPR.

0:30If you have a favorite wellness podcaster or influencer, you've probably heard about peptides at this point. These synthetic peptides are exploding in popularity. The injectable compounds are a string of amino acids and promise effects like weight loss, better sleep, muscle growth, and more. With promises like these, it may come as no surprise that there's been an explosion of interest and a market ready to provide. The loosely regulated market is already valued at around$140 billion and by 2033 is projected to reach over$290 billion. That's according to consulting firm West Monroe. Last month, an FDA advisory panel voted to make six peptides more accessible to the public, but FDA scientists warned against this decision, saying there's not enough data on their safety and effectiveness.

1:21Many people are already getting their hands on peptides through what's been called the gray market. What does the FDA's decision mean for access, and how safe are they? I'm Jen White. You're listening to the 1A Podcast. We look at those questions and more after this. Stay with us.

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2:39Learn more about Made in Cookware at m-a-d-e-i-n cookware.com. Let's meet our panel. Dr. Joshua Sharfstein is a public health professor at Johns Hopkins University. He's also a former FDA Principal Deputy Commissioner. Dr. Sharfstein, welcome. Thanks for having me. Also with us is Lauren Weber, the health and science accountability reporter at The Washington Post. Lauren, it's great to have you back. Thanks so much. And Jeff Cohen, the co-founder of the American Peptide Association. That's an industry association with a mission to help businesses within the peptide space and to set standards on safety, quality, and access.

3:16He's also a health law and peptide regulatory attorney. Jeff, thanks for joining us. Thanks for having me. Josh, I think it's good to start with just a basic understanding of what we're talking about here. You're a doctor. Perhaps the most recognizable synthetic peptide right now is a GLP-1. So that's brand names like Ozempic and Wagovi. But help us understand peptides and how they are typically taken by people. Sure. Well, like you said, peptides are short chains of amino acids. Amino acids are the building block of proteins. What we might call a peptide would be like up to 50 amino acids in a chain.

3:54A protein might have hundreds or thousands. So when I think of a peptide, I think of like a charm bracelet, but one that hasn't been tied around my wrist. So each charm is like an amino acid and you can put them in different order. Some of those the body makes, some of those can be made in a lab. You could do like star, star, star, heart, heart, or heart, star, heart, star, or, you know, you've got basically 20 peptides that come, 20 different amino acids that could be put in those different orders. The really important thing is that each order, each peptide is different chemically. It can have different effects in the body, can have different positive effects, different negative effects.

4:37And labs can tinker with different elements of this too. So it's like the amino acids with a little twist. And that's what a lot of pharmaceutical companies have done for different drugs that have gone through the approval process, including semaglutide and the other GLP-1s, there's a native GLP-1, which really is not that stable, but they changed the different chemical. Essentially, they added a little something to a charm or two, and then it becomes stable, and then they sell it once it's reviewed and approved by the FDA. So it's a little complicated, but if you think about it just as, you know, is this a charm bracelet that works or is this a charm bracelet that could be a big problem for me?

5:23That's kind of what we're talking about here. And most of these peptides are injected? That's right. Because in general, the body does a pretty good job of breaking down chains of amino acids when they're swallowed. And so for the most part, they're not going to have an effect unless they're injected and you avoid the stomach. Well, a member of our tech club writes, I'm a urologist and have been dealing with peptides for 30 years. Peptides are a confusing term. Insulin is a peptide and has been used as a medicine for over 100 years. They are not new. GLP-1s are also peptides, and then you have unregulated peptides.

6:03So this is where I think the distinction is really important, Jeff. So briefly, what do we know about the range of unregulated peptides that are available for people right now? Yeah, it's a great question. The vast majority of peptides that are being consumed by the public are unregulated. There's no clear thumbs up from the FDA on them. And yet that marketplace has existed for years. It just got amplified tremendously as a result of two things. One was pharma's marketing of GLPs. And the second thing that happened was that during COVID, the public's appetite for exploration and solving their own health issues really exploded.

6:49And Lauren, in your reporting, what else are you learning about what's contributing to the rise, not just in the popularity, but also the use of unregulated peptides? Well, I think it's important to note, too, that we have a health secretary, Robert F. Kennedy Jr., who's been very public about how he's a quote-unquote big fan of peptides. He went on Joe Rogan's podcast to talk about how he had used them for an injury and that to great effect in his own words. So you're seeing not only popularity of these products from influencers and celebrities and so on, but even from the top of the governmental health establishment and this resulting push at the FDA to potentially weigh making some of these peptides that available to compound pharmacies.

7:36Now, last month, as we said, an FDA advisory panel voted to make six peptides more readily available. That was out of seven they voted on. And the vote also reverses restrictions on about 20 peptides that were put in place in 2023 under the Biden administration over safety concerns. And those restrictions blocked compounding pharmacies from producing those peptides. Jeff, just briefly, what can you tell us about what these six peptides promise to do? Sure. You know, there's six of them, and basically they're all focused on longevity. They have the longevity and basically tissue repair. Those are the two things that I think that best describe how they function.

8:18And remarkable development. And the last one that didn't get moved was DSIP, which is really related to sleep quality. And it almost seemed like the committee was tired and had enough and just kind of punted that one. So. Yeah, we'll talk a little bit more about the makeup of that committee. But Lauren, prior to this vote, FDA scientists expressed skepticism about allowing these peptides to be more readily available. What did we hear from them? Yes, they issued several reports on each of the peptides saying that they felt like there was not enough data on the safety and effectiveness of the peptides themselves.

8:58They felt like there weren't enough clinical human studies to prove their effectiveness by the FDA standards that are typical today. I think it's also important, and we will, it sounds like, get into it, but there was some concern. My reporting, Rachel Rubine, has pointed out that FDA scientists were overruled in terms of who would be on this committee. And they felt like some of the folks that were on the committee had conflicts of interest. Yeah, we'll definitely get into that. But Josh, help us better understand what kind of testing has been done on these peptides. What is more typical, a more typical level of testing we see when we have approvals like this voted on by these committees?

9:37Sure. And I just want to clarify something. The vote of the committee is not binding on the FDA. There's been no action that the FDA has taken. What the FDA could do is propose to include certain peptides on a list that would permit them to be compounded. But the FDA has not yet done that. This was just an advisory meeting. And as Lauren said, it's an advisory meeting where there was a close vote that tracks specifically whether the members were involved with the peptide industry. So what the FDA does is still to be determined there. But I think the bigger question you're asking is a good one.

10:12What does it mean to be reviewed and approved by the FDA? It means that there are a bunch of different tests to assess the safety of a product because the FDA will not approve a medication unless it's safe in particular, unless the benefits exceed the risks. There are also studies to see if the medication does what the manufacturer says it does. If it's to treat ulcerative colitis, then it's to treat ulcerative colitis. If it's to help with wound healing, then they check. There's a study to see whether it actually works. And what we're talking about here are products that have not had those tests and they have not had those tests reviewed formally by the FDA.

10:52The FDA has not reviewed them for safety, has not reviewed them to see whether they do what they say they do. And when the scientists were presenting to the advisory committee, they said, based on what little data we see out there, we're not confident about either of those things. And not only that, they weren't even sure whether the actual product could be specifically characterized. So in other words, what people may buy as a peptide may actually be different chemicals underneath that have different effects. So typically, the FDA wants to know exactly what the chemical is, that it's safe and effective.

11:27Here, the FDA is saying we don't know what the chemical is. And based on the kinds of data that we can see, we can't be confident that it's safe or effective. That's the difference between an approved or what we're calling now an unregulated peptide. And so, Lauren, just briefly walk us through exactly what happens next. Now that this advisory committee has made this vote, what are the next steps? Well, as Josh pointed out, the FDA still has to decide how it rules on this. But there has been some, you know, as the Post or the Washington Post has reported, as the New York Times has reported, There are concerns that, considering this is a huge effort from Kennedy, that he may tip the scales to overrule the FDA scientists and follow the vote of the advisory committee that he also may have had a hand in picking.

12:15We have to take a quick break, but when we come back, we get to the people who served on this advisory committee and more back in just a moment.

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13:55Back now to the exploding popularity of synthetic peptides. And Lauren, before the break, we were talking about who's on this FDA advisory panel that voted to make these peptides more widely available. These are outside advisors. They don't work for the FDA. But your colleague, Rachel Rubin, reported that officials inside the FDA expressed concerns over potential conflicts of interest. What more can you tell us about the people on the panel? Yeah. I mean, so seven of them that we found in our reporting had business ties to peptides. That includes one of them who ran a substack titled The Syringe Runneth Over, which talked about his using of peptides.

14:35You have another one who's a chief medical officer at a wellness apparatus that sells peptides, others that promote peptides to treat aging and fatigue and so on. And so, So, you know, when we talked to some experts about this, they said, look, you know, some folks were like, this is a blatant conflict of interest. I mean, these people have business interests in promoting peptides. However, you know, one gentleman who runs the Alliance for Compounding Pharmacy said, you know, told us at the Post that, look, you know, these people actually have real-life experience dealing with peptides. So it's helpful to not just talk to academics, but also talk to these folks as well.

15:12So there's definitely some complaints, though, from a wide variety of ethical experts that these folks have financial ties to the decision that they were part of. I just want to note that we did reach out to all eight of the panel advisory members who voted to bring these peptides to the public. One was not available, while seven didn't respond to our request. Now, Jeff, we mentioned the amount of money this market is expected to generate. The peptide market could reach$295 billion by 2033. What concerns, if any, do you have that these peptides are being greenlit because of their potential market value at the expense of American safety?

15:48Yeah, I mean, it's a really meaningful concern that because there's a lack of uniformity as it relates to manufacturing quality and testing standards, that the quality safety issues woggle too much and now the public access suffers. So because of that, the APA is completely committed to insourcing industry insider information on what the technical standards need to be in terms of manufacturing and testing. And we believe that if we get that done this year and report that upstream to regulators and journalists and what have you, we're going to create some safety, some quality, and maintain access.

16:32Now, Jeff, I just want to pause briefly because I need you to just explain something in layman's terms for us. You said insourcing insider information. I just need you to put that in everyday language. You bet. The APA has as its members people that are actually involved in making peptides, distributing them, testing them for safety and quality. And because we have access to that community, it's important for us to get that information out of them and to create standards that ensure safety and quality. Josh, I mean, your response to Jeff's assertion here that what needs to happen needs to happen within the industry itself?

17:17Or do you think that there's a different process that these currently unregulated peptides need to go through? Well, I think safety and quality are very important. And I think effectiveness and whether things do what they say they do is also pretty important. I do would point out that for most medications out there, there's a standard of quality that's set outside of the industry so that different companies can reach it. But I'm kind of curious what the American Peptide Association is thinking when you say safety, like what safety tests will be expected for these products? Jeff, go ahead. Yeah, great question.

18:00You know, right now there's no consensus on what needs to be tested and what the specific outcomes need to be on each panel tested. That has to be agreed on because some folks are testing for sterility but not potency. Some are testing for sterility and potency but defining it differently. we've got to come up with what really high integrity testing means, what has to be tested, and what safe outcomes metrics need to be on each one of those tests. So Josh, when you hear that explanation, yeah, I want to hear your thoughts. You know, I think manufacturing standards absolutely include things like sterility.

18:43And having a manufacturing standard sounds like something that Jeff and I would agree on for any product, although I think it's good for it to be set independently. But I think the existence of a manufacturing standard is important. But none of that has to do with safety. You know, I think about safety. I think about, does it shut your kidneys down? Do you have a liver challenge? There's also a big safety issue with some of these that they promote the growth of blood vessels, which can actually turn cancers into quite potent threats for people. So, you know, Whether or not you get really sick when you take a peptide or any other medication is not just a question of whether it's sterile, but what the actual effect it has on the body.

19:28That's why the FDA has learned a lot over the last hundred years on how to test products, very potent biological products, of which peptides absolutely are, to figure out whether it's safe in the short term, medium term, and long term for people to take them. And I hope we could agree, if we agree on safety, that that knowledge should be brought to bear and that any product you're injecting should be subjected to basic proven safety studies, not just sterility and manufacturing standards. Jeff, is that something the APA agrees on, that the sort of safety standards Josh is describing there are necessary for the industry?

20:07Absolutely. You know, from a timeline perspective, it's just much more attainable to come up with what safety means as it relates to manufacturing and testing. Efficacy, long-term impact. The problem in this space is that these products have really been treated more like supplements than they have as drugs. You know, the PCAC, the advisory committee meeting that just concluded and it's going to reemerge in February. They're used to looking at drugs that are owned by companies that can afford to spend$10 million on double-blind studies for safety and efficacy. The problem in this space is that a lot of these chemicals, they're not owned by any company.

20:52So nobody's going to invest that$10 million, which is one of the reasons why you see all of this whole testing and proof and efficacy. Those studies are out there, but they're limited, they're scattered, and there's been very little until now to try to string them all together and really do meaningful data collection. So that makes me wonder, Jeff, is that not then an argument for pausing on making some of these synthetic peptides more available to the public, the lack of information and safety standards that both you and Josh are describing? Well, you know, it's a great question because that consumer demand has been massive, and it's been massive for years.

21:41And yet there was no attempt to kind of ratchet access down or address any of these issues until the fall of 24. That's right after pharma convinced the FDA that the shortage of GLPs was over. And so there was ever since that point, there's been a massive push by pharma to control, limit the access by the public to competing GLP weight loss peptides. And that's where all of these regulations at the state and federal level arise and where all these conversations are emanating. Lauren, I'm hearing sort of two different arguments here or conversations. One is about, you know, research-based evidence around the effectiveness and safety of synthetic peptides, the currently unregulated ones.

22:35Like we said, you know, you have other ones like Ozempic and Wagovi and insulin have gone through that kind of testing. But then there's also this question about the market demand, the consumer demand for these products. In your reporting, what's driving the current push to move some of these synthetic peptides to the market? Is it really that market demand that's driving the conversation right now? How much traction do the safety questions have in the way this is playing out? Well, when it comes to how the FDA has been addressing this, there's been some concerns, you know, as we talked about earlier, that, you know, a lot of this is partially from the push from Kennedy.

23:16You know, Kennedy himself, the HHS secretary, has also, to Jeff's point, likens peptides to supplements. And supplements are not regulated in the same way that drugs are. They don't go through the same safety or efficacy testing. And, you know, Kennedy, proposes this push to move, to make access to these peptides more available through compounding pharmacies. He says it would be helping solve the gray and black market problems. But his own FDA scientists say there's not enough safety and efficacy to use the FDA in that way. So, I mean, there's a lot of debate around this. And at the end of the day, to Jeff's point, there is just a lot of demand.

23:53So people are going outside of regulated channels to access these unregulated peptides anyways. And I did a larger investigation in what that looks like at the state, local, and federal level. And the bottom line is, is these peptides are falling through the regulatory gaps. I want to talk a bit more about the grain market in a moment, but we're getting questions about safety and continued research of GLP-1s. One listener emails, my husband was placed on Ozempic because he is diabetic and has had two heart attacks. How safe is this for him to be using? Joshua, I want to come to you on that, but I first want to just make sure we make it clear that anything you hear from experts here on this program is not a replacement for your own doctor's guidance and advice.

24:37But Joshua, what do we know about the longer-term safety of Ozempec? Sure. Well, first of all, we know a lot about the shorter-term safety of Ozempec because those studies that I was talking about have been done because it went through the FDA review and approval process. And I really appreciate that Jeff seems to support doing really good safety studies, including human trials, to make sure that products are safe before people inject them in their body. For Wingovi, there's a lot of evidence from different clinical trials. And then there's now a lot of evidence from actual experience. And the evidence looks pretty good that this particular peptide not only addresses weight loss, but also improves cardiovascular health.

25:22For any particular advice, I certainly would suggest talking to your doctor, but it's a totally reasonable thing. I'm a pediatrician, by the way, so I really am a couple steps away from actual medical advice here. But, you know, I think that this is what these medications are increasingly being used for. And it's great when there's a peptide that is safe and works and it can save lives. Insulin has saved so many lives. But let me tell you a story about a product that was being sold alongside insulin. It was called Banbar. It was another product. There was a manufacturer who was out there claiming that it was great for diabetes.

25:58FDA at the time didn't have the authority to do real meaningful oversight and require products to do safety testing, efficacy testing. Turns out it was worthless. But they were getting people to take that medication instead of insulin, which had just been invented, won the Nobel Prize. And as a result, people died. The FDA actually had a traveling exhibit, which on the one side showed testimonials, people saying, I swear to God, ban bar, save my life. And then on the other panel was their death certificate. And the lesson from that was the Food, Drug, and Cosmetic Act, among other things, basically saying we need real evidence.