Ozempic, public health, and black markets

Gavin and Jessamy are joined by Oksana Pyzik (UCL, Fight The Fakes Alliance) to discuss how Ozempic/Wegovy/semaglutide works, what becoming mainstream means for our understanding of obesity and public health, and how demand is fuelling an unregulated black market in the drugs.

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Transcript

This transcript was automatically generated using speech recognition technology and may differ from the original audio. In citing or otherwise referring to the contents of this podcast, please ensure that you are quoting the recorded audio rather than this transcript.

Gavin: Hello, and welcome to The Lancet Voice. It's July 2024, I'm Gavin Cleaver, and I'm joined as ever by my co host, Jessamy Bagnall. Today, we're turning our attention to Azempic, a drug that's been making headlines for its popularity and potential in managing diabetes and weight loss. But with the great demand for the drug comes a lot of concern as a black market for Azempic emerges, raising critical public health issues.

Oksana Pizek from the UCL School of Pharmacy and the executive board member of the Fight the Fakes Alliance joins Jessamy and I today to discuss the pros and cons of the current state of the Azempic market.

We're here to talk about Ozempic, which obviously is massive across the news at the moment. There's all sorts of stories about, no celebrities using it, but it becoming quite a regular drug in the general population as well. So perhaps we can kick off with just a quick introduction.

Recap, what is Ozempic? What does it do? How does it work? 

Oksana: Yes. So Ozempic is the brand name so Novo Nordisk produces it but the active pharmaceutical ingredient is semaglutide. And it's, was originally developed to treat type two diabetes and it mimics a naturally producing hormone called glucagon like peptide GLP 1s.

And these regulate blood sugar and appetite. It slows digestion, it increases insulin production and it reduces appetite. So it, Prolongs to tidy that feeling of fullness. So 

Jessamy: just for listeners, there's a Zempik in Wegovy, isn't there? Just briefly tell us what the difference is, and over the last couple of years we've had lots of news coverage about Wegovy and then it changed to a Zempik.

But they're doing the same thing essentially, but indications for different diseases. 

Oksana: Yeah, absolutely. So Ozempic and Wegovy are both the same drug. It's semaglutide. Where it's slightly different is the indication. So that's what we use it for. So Wegovy is used for weight loss only and was approved in for this in 2021.

And it starts at a slightly higher dose. Your titration is goes up more. So you will work up higher to a max of about 2. 4 milligrams weekly, whereas with Ozempic, you start at 0. 5 and you usually top off at two. So again, same thing. It's the exact same drug, but it is used for, in some instances, Ozempic is licensed only for diabetes and Wigo V, that's the trade name, and that's for weight management.

But there are a whole host of really new and interesting other drugs in development that have even more profound effects. And those are coming soon. Coming down the pipeline quite soon. So they work in a slightly different way. You might have heard of something called moon jar. Oh, and this was approved in May.

2000, and That active ingredient is actually trizepatide. It has the same GLP 1 receptor agonist, but also, it the glucose dependent insulintropic polypeptide, a GIP, receptor agonist, and this, so these two things working together maximizes the benefits. So it increases the body's ability to recognize and use circulating insulin, as well as all of those sort of other benefits that we talked about with the other drugs.

Appetite suppression and stimulating insulin. So this field is quickly evolving, I'd say. 

Jessamy: That's right, isn't it? And in fact, there are many other indications that the pharma companies are looking at that semaglutide might be beneficial for things like, heart problems, things like, I've seen Alzheimer's, Parkinson's, maybe you could just take us through some of those things and.

Where the sort of, where the scientific evidence lies at the moment or what, where we're expecting there might be some benefit. 

Oksana: Yeah. So all three medications currently are once weekly subcutaneous under the skin injections and they start in this sort of low dose and increase to, to maintenance dose, but you're absolutely right.

What is very interesting is that because we see obesity, diabetes being so strongly linked with cardiovascular disease, with stroke and with neurological disorders, that there is this belief that there can be protection to the body. against these through the use of these weight loss injections.

So the compound benefits then fall under that weight loss indication. 

Jessamy: But in fact, but they're also being looked at for other indications outside of cardiometabolic disease as well. And it's interesting to, I don't fully understand, and I don't think anybody really understands what mechanisms we're looking at, whether it's anti inflammatory or.

It's very interesting. 

Oksana: And I think we, it's, we don't know the full picture. And I think in some, compound benefits that we've been discussing, but there's also, I think the flip side of that, because we don't know everything what other risks are possible with these medications.

So you're absolutely right that It is being looked at for heart disease, sleep apnea, kidney disease, PCOS, even things like substance use disorder because of the addiction aspect and reducing that dopamine hit associated with either things like gambling but also overeating. There's a real crossover there.

And I think that neurological mechanism is yet to be fully understood. 

Gavin: I was going to say, presumably, we don't have a lot of long term data on it. 

Oksana: So most of the data currently, and it isn't that new, it has been used over a period of time for diabetes. So in diabetic patients, there is a lot of data at a population level.

And in that There is confidence around general safety of its use. But I think where the issue lies is that diabetes in itself is a degenerative condition. And so a lot of the issues that a patient might present with could be just. Filed under a complication of diabetes rather than it being explored further as a consequence of using semaglutide.

Jessamy: That's interesting. Maybe we could just go back to the weight loss thing. What kind of weight loss can people expect when they're taking a Zempik or Widovian? How does that compare to, some of the other interventions that we have in terms of bariatric 

Oksana: surgery? It leads to, so if we look at Ozempic or Wigowi, it leads to about 15 percent of body weight reduction over a year when combined with lifestyle changes.

However, about 10 to 15 percent of people do not lose any weight and we don't know why. So there'll be failure to respond. However, it's, Although that is quite drastic, if we compare that to placebo and trial weight loss was about 2. 5 percent versus 15%. That's a dramatic difference. However, there, if you look, only about 10 percent of the participants were able to keep off all the weight.

Coming off of the drug, meant that most people would gain at least some on average, more than 50 percent of the weight back, and only 10 percent maintain the full weight loss aspect. So there is this also concern that some people may end up just having to take this medication for the life course and it being treated More as a chronic disease and in that case, this wouldn't be too dissimilar to let's say those taking statins or if you think about hypertens antihypertensives often patients do take these for the life course.

Jessamy: So what we're saying basically is when you're on the drug, you can expect most people are seeing some kind of weight loss, but when we compare it to other interventions that we have, like bariatric surgery, they tend to last for a longer time. It's not that they don't completely reverse. There are some patients that have bariatric surgery and put on the weight afterwards or it fails, but for the most part, it's a kind of, it's a longer term perspective.

We've talked about some of the benefits and excitement, but there's also been a lot of concern, a lot of criticism about, not only the way that these drugs have come onto the market, accessibility, who's getting them, very much on a kind of first come, first serve, who's able to pay, but there are other aspects as well about, the public health implications of focusing on a drug when actually we all live in such an obesogenic environment, have we got our priorities right?

Maybe you could just walk us through some of these. The narratives that that we've all probably seen in commentaries and discussions about where the concern lies with this, the moral, the ethical, the public health aspects and your own kind of particular perspective from a global health pharmacy point of view.

Oksana: Yes, absolutely. But I'm going to just jump back because I feel I didn't actually fully answer your previous question. Don't worry about that. You did. But yeah, 

Jessamy: go 

Oksana: for it. 

Jessamy: Go for it. 

Oksana: Yeah. Yeah. So I talked first about how if we compare perhaps that the three different methods. So if we go with Ozempic.

You can lead to 15 percent body weight reduction, which has significant health benefits. A lot of individuals would say that the GLP 1s are right up there in terms of public health benefit as vaccinations and sanitation in terms of expanding lifespan. So that's really interesting. Now, if we talk about Munjaro, that weight loss goes up to even more.

So 21. 4 percent of body weight loss on average, again, after years of use and If, but bariatric surgery still is you can lose the most amount. So it depends on the type of procedure. But if you have a after sleeve gastrectomy ranges between 30 to 80%, that's a huge window. I appreciate that, but it is much higher than both of the medicines.

Now, not everyone's going to be an appropriate candidate for that, particularly when the amount of weight that needs to be lost. is not as high. So who makes an appropriate candidate for bariatric surgery are usually those with very high BMIs where actually using just a semaglutide or GLP 1 type product would not lead to enough of a weight loss.

In that instance, it would be the best option, but of course, it being quite an invasive procedure, that's going to be inappropriate for a significant patient. Part of the population but it is very, the results that you can gain with it are very dramatic. 

Jessamy: That's right. And that's exactly what I was going to say is, these are major operations that happen under general aesthetic.

They completely change people's lifestyles. Their ability to eat certain things is massively diminished that their whole approach to food and diet changes after. Some form of bariatric surgery and it comes with a whole suite of complications that can happen on the table and you know lasting effects afterwards So that's exactly right in terms of all of these different Perspectives and characteristics and they're going to make some people more You know likely to want to take a pill and other people more likely to want to have some kind of definitive operation 

Oksana: Yeah.

And in some ways it's much easier to just stop an injection or stop taking an oral medication. So in terms of it, that change in lifestyle becomes untenable. There is a clearer path or an easier path to returning to baseline where the complications and living with that for the rest of one's life is something that shouldn't be taken lightly.

Okay. Thank you. 

Jessamy: Yeah, absolutely. Okay. So great. So now let's go let's jump forward to where we were before. I think that's a great answer to thinking about, some of the concerns that people have raised over the last sort of couple of years in terms of access, availability. Resource allocation, public health aspects over to you.

Oksana: This is the new hot blockbuster drug on the market. So it's very interesting to see that in Denmark where Novo Nardisk manufacturers are based, it's driving the entire economy. Their profits surpassed GDP of Denmark and What we are seeing is that the glamorization of this type of medication and this I think is Definitely not true for all medicines, They don't have that same halo effect Shortages happen frequently when there are things like let's say a global pandemic but for more Transcripts The thing that this reminds me the most of is perhaps Viagra, where there was in the initial response so many people selling it illegitimately online because the demand of something that was new and hot.

That came out and there was very little regulation in that space, but the demand for this is even higher given just the number of people affected. So if we look at sort of obesity rates in the UK, It's close to 26 percent in the US. It's closer to 44%, which is significantly higher. But if you include overweight in that category, that thing goes up to 70%.

So you're looking at a drug that maybe 70 percent of the population could be eligible for use. And then you have what I call the Hollywood effect where people use it to become as slim as possible rather than for, because. Because they, they meet the health criteria, which you know, being obese, having a higher BMI would be the baseline entry.

And that's not the case universally. And as a result of that many diabetics, many people who are the most need cannot access it. And this has been. In headlines for the past two years, and even now, manufacturers are struggling to keep up with the demand as more competition arises. This will likely expand access and perhaps cost will go down.

But we're looking at A drug that in the U. S. would cost about a thousand dollars a month. Here in the U. K. It'll run you a couple hundred. But in the U. S. again, the largest market. only 25 percent of insurers will actually even cover the medication. So this then creates a even more divide between what the intention of the drug should be, which is to lower The health risk for those most at need and essentially that's not what's happening and the health inequity gap.

It is growing for this. Not just in the US, but globally and those with the means and access to a private GP here. Our first in line will be able to gain access more easily than those going through other avenues and it's taking much longer because it's taking so much longer people then turn to all sorts of different places to try to get their medicine, whether that's social media.

Or websites that claim to be pharmacies, but are not and they could be receiving anything from insulin to just saline solution. And of course, if you're injecting yourself with insulin that hypoglycemic drop can lead to hospitalization complications and invulnerable people, even death. 

Gavin: I was going to say it's the perfect ingredient for the perfect set of ingredients for a black market, isn't it?

Because you've got this. Brand name recognition now from the drug name. Everyone knows what it is He said that's got that kind of hollywood factor to it plus the kind of lack of availability plus the prohibitive cost it really can be a bit of a public health disaster Absolutely, 

Oksana: and I think that we are not really doing enough in this space to educate people about How to access these types of medications that you re, it requires a prescription and if you're going on to a website where you're not being screened or asked for a prescription, then what health risks you are taking on board with that and that it should be a red flag if you're getting something delivered to your house where you're given instructions on how to constitute it, how to mix it together, where it actually says not for human use.

These are not even sophisticated falsified or counterfeit medications. The opposite, there are, again, due to shortages where organized criminal groups have run very sophisticated operations so that they can infiltrate even the legal supply chain. So that has happened in the U S. With a fake Azempic being 10, 000 unit units of it being identified.

And the only way that they were able to distinguish it even is that there was an additional barcode on the product. And, Other than that was an identical and because it's so hard to get the product what ends up happening is wholesalers are not able to fill their demand from a trusted seller. And so then they may.

Turn to whoever is providing it and it's not that difficult to forge documents, etc. So in that aspect even the legal supply chain is at risk. And this is why recently the WHO for the first time ever put out a alert on ozempic and semaglutide products because of the cases in the UK, the U S and Brazil.

where it did infiltrate the legal supply chain. Now this will be at a much lower scale. The real risk in my mind and the real public health threat here is people trying not being able to get it through their clinics or GPs and turning to fake websites social media. And even in some cases, things like hair salons where, or these medical type spas where they are also selling these products without any assurance that it is the legitimate product.

Gavin: Yeah, so are there other kind of plans in place to I guess given you said that it's you know It's the current income is larger than Denmark's GDP for Nova Nordisk at the moment I'd imagine there are plans in place to massively speed up production, but we're not there yet. 

Oksana: No, it will take some time So we're not there yet.

But I think the overall anti obesity medication market could reach 130 billion by 2030. And that's research coming out of Goldman Sachs analysts. It's a big sector and already this is being, because it's so profitable in that sense, it's another reason that it's being targeted.

The shortages, of course. Are part of that picture, but overall the falsified medicines market is estimated to be worth about 200 billion American dollars. And that means that with such a high reward and low risk, there isn't really uniform legislation or penalties. You get less jail time for selling fake cancer drugs than for selling heroin, right?

In that aspect, it's the perfect crime in a way because it's easy to make money and it's hard to get caught and people are buying things that they come across on Instagram because the algorithms encourage it, right? As soon as you start looking at these products, the algorithms are going to feed you more and more of the ads.

So we also need to put pressure on the tech companies. To regulate and they have right now they are exempt from any account of any type of accountability so There have been cases of other falsified medicines in the U. S. where teens have died and those ads have remained up on those social media platforms, even after parents have contacted authorities, the companies themselves, Told them about it and no action was taken So there are these parent led activist groups predominantly in the united states that are trying to introduce new bills Where they will be these companies the social media companies will be compelled and mandated to remove ads now, of course new ones can crop up in their place And if there are hundreds of millions of people trying to sell you ozempic then You know, you're not going to totally eliminate the problem.

But if we take away the incentives, if there is an actual consequence and more uniform regulation, then we can make a big dent in the problem. Even simple things like making sure that pharmacy domain names are protected so people can't get confused and think that they're accessing a legitimate pharmacy website.

I think most of the population And then I'd actually pose the question back to you is do you know how to verify that this is an actually legit pharmacy or not when you visit something like claiming to be boots? 

Gavin: No that's true. I guess I don't have a verification system. No. 

Oksana: So it does exist.

It's just People are not aware of it. So it's not a very effective verification system. And most of the time it'll be either at the top or the bottom of the page. And you've got to stroll and click on the in Europe, they have the European wide common logo. And this tends to be a green cross with the flag, depending on which country you're in.

In America, they call it the VIP system. As you click on this, a pop up will appear and it'll tell you, yes, This is a pharmacy that is registered with the General Pharmaceutical Council. It is legit. And if there are any concerns with them, you will be able to read about if they've been flagged up with the regulator or not.

But most even other healthcare professionals are unaware of how to verify A legitimate pharmacy website, and this is why particularly where drugs are expensive, any website, and I'm Canadian, so any website claiming to be canadadrugs. com or something similar is usually a way to make Particularly American patients feel that they're accessing a legal pharmacy, but just getting the benefits of a Canadian healthcare system and has nothing to do with Canada.

It's often in a, other side of the world operations. And it's easy to just stick on a flag and a person in a white coat and be, appear for there to be trust with the public. So a lot of work to do in this area, I think. I 

Jessamy: think you've really comprehensively laid out a lot of the concerns, Oksana, and I think you've done it so well.

What I'm hearing is that there's something here about You know manufacturing that we actually have to increase the production that's going to take some time and then the two levers in the Interim are about education and about regulation what body or is are there any international bodies or Sort of organizations that are taking ownership of trying to push and lobby for those interventions on education and regulation.

Oksana: Sure. So I'm going to talk about Fight the Fakes because that's one that I'm very involved with. And this is a group, it's a non profit, but a group of Essentially volunteer organizations who come together to raise awareness on the issue. For more specific tools, there are things like the MediCrime Convention, which is a type of legislation that has been adopted in several countries, including even Ukraine, where There is a big problem with falsified medicines due to the full scale Russian invasion.

However, even if countries sign up to, for this medicrime convention, which would mean that they promise to adopt a type of legislation that is more strict on falsified medications as a crime. And Issue more severe penalties as a result. It's not enforceable So it's that is one step in terms of the uk is not has not joined the medicron convention To harmonize legislation in this area Many of our eu counterparts have and international partners.

But again, this feeds it directly into toughening up on criminal sales of fake medicines and disincentivizing it We talked earlier about how the social media algorithms. Push a lot of these fake seller accounts in addition to that, now there are things like online phishing attempts offering fake GLP 1 agonists to patients and that increased by 183% in the first quarter of 2024 compared to the same period last year.

And this It's coming from McAfee, the security agency. So another word of warning, if you're being pushed, GLP1 is agonist in your email, be very careful about clicking on these links. 

Gavin: Yeah, I think longtime listeners will know that it's one of my favorite. Constant bugbears how poorly regulated things like this are on the internet if it feels like Policy never really caught up to the invention of the internet constantly playing catch up with it You touched on it a couple of answers ago, but i'm very interested in what sort of penalties are there for?

Supplying Fake pharmaceutical goods and what sort of progress would you like to see made in that area policy wise? 

Oksana: Yeah, so usually, depending on the scale of the operation certainly fines in some instances jail time as well. But there's just, there is such a wide range of sometimes just a slap on the wrist.

To other countries taking it much more seriously, and I think that's where there is such little Again, police forces are stretched. Law enforcement is not very well trained in this area particularly in low income settings where this problem it goes way beyond just Ozempic, which is the current hot drug of the moment.

It goes down to essential medicines that aren't necessarily even very expensive I'm thinking about things like the pediatric syrups and the now hundreds, if not thousands of kids who have died as a result of contaminated cough syrups, teething syrups. And in this instance, it was actually traced back to a legitimate manufacturer in India, which the Indian government has.

cleared them of any wrongdoing, but the WHO was able to identify diethylene glycol DEG. This is an industrial solvent often used in antifreeze and brake fluid. And they were able to find high amounts of this in the product. This led to children ingesting it and developing acute kidney injury and dying within days of taking this.

Syrup, and it got so bad to the point that the WHO advised countries that because they cannot assure the quality of these products That they should just tell all parents not to get any over the counter pediatric syrups for the time being and There is no accountability. Still, this is ongoing. But there have been excellent investigative reports about this in Reuters and many other outlets tracing.

Gambia was affected, Uzbekistan, Iraq, Nigeria, and we continuously see this every five to ten years, and it's on a much bigger scale than the what we're talking about today, which is Ozempic. 

Gavin: Yes. I was going to say, the adulteration of consumer goods is pretty much a tale as old as time really, isn't it?

Oksana: Yeah. That's why the FDA was invented, right? In the 1930s. Exactly because of this diethylene glycol contamination. So the reason it gets used is that it's similar in viscosity to glycerin. So it's a swap out or you can also have. Again, the more fractured a supply chain, if your excipients are not tested, if your excipients aren't quality assured, then you can get contaminations through that way.

So usually if a drug price or excipient is so low, it's so cheap, then it's too good to be true. 

Gavin: Yeah, absolutely. I guess finally I wanted to know generally your opinion, where do you see the future of these weight loss management drugs? Going. 

Oksana: Yeah. And it, I think Jess touched on this a bit earlier in terms of how it does not solve the underlying public health issue on how ultra processed foods are so prevalent in not just our supermarkets, but in every street corner and how we're not making the healthy choice, the easy choice, and that the solution towards what is quite.

A broken food system being to use a medication where you inject yourself weekly to Not to break an addiction to it is a very much a band aid problem, and we are not going to be able to have every obese person access this medication, even with ramped up supplies. There are, we need a healthier population.

There's strong economic reasons to, and public health reasons for make ensuring that there is lower rates of obesity. And we shouldn't only be relying on one tool because ozempic is a very powerful tool for weight loss, but it has to be coupled with systemic changes and with ensuring that we are investing in healthy foods available at schools, particularly with the Rise of childhood obesity with ensuring that we have access to fresh foods in a way that's affordable for everyone And that's a much more expensive solution, but it's one that has a much more lasting power than expecting the, what is now in the U.

S., the majority of the population having to rely on a pharmaceutical tool. It is revolutionary in many ways, but the real revolution has to come from the health systems and the food systems working together for public health goals. 

Gavin: Yeah. In that way, it's just the kind of another very useful, like you said, revolutionary tool, but a flawed tool.

In the kind of the broader public health issues that we've been trying to tackle for decades in terms of obesity 

Oksana: And it's like any medicine not without its own risks, right? There are Every medicine has a side effect and this is why it should really be that the benefits clearly lie with those that have the highest health risk due to obesity.

And what I'm very worried about is it getting into the hands, particularly young people those with eating disorders. And that's why I don't think that there've been people calling for semi glutide to become available over the counter. And I think that would be disastrous for that reason.

There are significant benefits. to this medication, but particularly for those who are already quite sick, a young and healthy person. And I'm thinking particularly around young girls who. may see again this sort of the Hollywood glamourization of using a Zampak to lose weight, to fit into a dress lots of rumors about which celebrities are currently using it and not using it.

There is very little discussion about what the consequences are for Those people the healthy weight starting very quite young on it and then continuing on we know that it's not just fat loss But you also lose muscle when you are taking these medications and from the age of 30 onwards you're already losing a significant amount of Muscle every year.

So if you take that from a very young age up until Your elderly years, you're at much higher risk of things like falls, of not actually being strong enough to move around and be mobile. And I don't think people necessarily think about it in those terms. And It's without question that, someone who is high risk for heart attack, stroke, et cetera, is a great candidate for this.

Even if it means that there are higher risks for pancreatitis, that again, they could be losing up to 20 to 30 percent of lean muscle mass by taking this medication as well and accelerating that as they get older or that they could get things like stomach paralysis or. Gastroparesis, which is a more severe disorder.

And again, there are actually lawsuits in the United States linked to this. So all of these medications aren't without potential complications. Some people tolerate it really well. And of course, it won't experience the more, most severe aspects, but it needs to be part of the equation that people consider whether it's right for them or not.

And someone who is on the border line will. That ratio of risk versus benefit is going to look really quite different I'd be interested to see the future studies on depression and mental health, how this medication affects that. I think we need a lot more information in that area because there have been In some cases, reports of things like low mood and whether that's linked to having less of a response to all sorts of activities and pleasures that stimulate dopamine.

That part, I think we will understand more with further research, but. I think it's something that we should really also think about how are we going to protect our young people who might want to access this medication for the wrong reasons. 

Gavin: Yeah, I suppose the danger in that sense is it becoming more of a lifestyle choice than a, a medical tool for people who, for whom the disadvantage of taking a Zempig would outweigh the problems they face from their existing conditions.

Oxana it's been wonderful to have you on again. Thanks so much for this incredible overview and for sharing your time and opinions with us. We really appreciate it. 

Oksana: It's been great to chat to you both.

Gavin: Thanks so much for listening to this episode of The Lancet Voice. Remember, you can subscribe to The Lancet Voice wherever you usually get your podcasts and we'll see you again next time here at The 

Lancet Voice.