Ben Locwin
Vice President of Reliant Life Sciences
Ben Locwin brings deep insight as a healthcare executive, medical scientist, TEDx speaker, and frequent contributor to outlets like The Wall Street Journal, Forbes, and NPR.
The Rise of GLP-1 Drugs: Transforming Weight Loss Treatment
Balancing the Future Episode 2 Season 2
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Episode Transcript
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Ben Locwin: As GLP ones are enjoying this incredible rise, what is that also meaning for the existing capacity out in the market for any other treatment that might be out there?
Chai: If you haven't heard of GLP ones, you've almost definitely seen the brand names, Ozempic, Lago, and Majaro.
Micah: These drugs were originally developed in the 1970s to treat diabetes. But now they're making headlines for a very different reason. Weight loss
Chai: with some people losing 15 to 20% of their body fat, it's hard not to wonder what else can GLP ones do?
And just as important, what are the concerns we're not talking about?
Ben Locwin: It seems to be that based on large scale population data, that there's the potential to have GLP ones effective for chronic kidney disease, for some liver conditions, for certain cardiac diseases.
Micah: In this episode, we're diving into the science behind this.
Weight loss, cultural phenomenon. We'll break down how these drugs work, why their injectable form is sparking sustainability concerns and what other surprising uses they might have.
Chai: I'm Chai Nussbaumer.
Micah: And I'm Micah Schweitzer. This is Balancing the Future from METTLER TOLEDO.
Chai: On this show, we delve into the world of science and technology and.
Explore its transformative impact on our lives.
So we hear a lot about GLP one or Ozempic for obesity. There's even a fun jingle. Oh, Exem ppic, which kind of became famous. Yeah, but how did it become a major treatment for weight loss?
Micah: Nice singing. Kai.
Chai: Thank you Micah.
Ben Locwin: Yeah, so these GLP one drugs are very interesting. So it's an acronym for glucagon like Peptide one receptor Modulators.
And these molecules, they have a long history dating back five decades. They were initially investigated for insulin control for diabetes, maybe contrary to popular belief. It was realized very early on in their development process and life cycle that they were. Also supremely effective for weight loss as well.
But it wasn't something that was just discovered late in the game by a lucky few patients who were taking it for, uh, blood sugar control and then said, oh, and by the way, I've lost a significant amount of weight. It was known very early on that they would have that potential.
Micah: To help us navigate this world of GLP ones, we've brought in Ben Locwin Locklin.
Ben Locwin is the chief scientist and head of clinical services at Black Diamond Networks. He's also a TEDx speaker, a podcaster, and has been featured by outlets like the Wall Street Journal, Forbes, and NPR.
Chai: And so how would you say that GLP one drugs compared to other weight loss therapies on the market, such as, uh, bariatric surgery, other medications, or lifestyle interventions?
Ben Locwin: Yeah, I think compared to other lifestyle interventions, other surgeries, other medications, a lot of the historical weight loss medications were predominantly central nervous system stimulants. So the idea would be to increase the body's thermogenesis, the rate at which it burns calories by stimulating, increasing your basal metabolic rate.
Those always brought with them a lot of off target effects, a lot of side effects, nervousness, anxiety, irritability. A lot of cardiac syndromes owing to increased respiration and heart rate. The GLP one drugs have shown themselves to be incredibly successful at rapid weight loss, and for that, their use, of course, has gone viral by influencers on social media.
Created a lot of buzz. Patients can lose 15, 20, sometimes 25% or more of their body weight while on therapy. But you know, while other modalities have worked well, the GLP ones offer a non-surgical approach compared with gastric bypass bariatric surgeries. Now lifestyle interventions are always interesting because they can be preferable for long-term change because when patients have stopped taking their GLP one medications, for example, they tend to regain their lost weight fairly rapidly, and particularly if they haven't made lifestyle modifications.
Given the tendency of people to revert to old behaviors, not realize how much they were or how much they are eating and underestimating maybe how much they're exercising, you get a lot of differential effects there. So it would be great to have everybody on lifestyle interventions, but you know, when people are looking for maybe a fast way to shed a lot of body weight, certainly the GLP ones have been incredibly successful at that.
Chai: So you would say it's more of a, a compliment instead of a, a supplement?
Ben Locwin: Yeah, definitely. Complimentary would be better.
Micah: In the sort of viral social media environment in which the weight loss aspects of GLP one have taken off, are there any, it's sort of presented as a, as this, you know, silver bullet or magic solution in some ways.
Are there side effects that people need to be aware of or careful about?
Ben Locwin: Yeah. You know, like any drug, there are always side effects, but with the GLP ones, particularly because they have a strong influence on the gastrointestinal system, you know, there's a lot of reports of nausea, diarrhea, uncomfortable situations for people which have led to them discontinuing therapy.
It seems like a lot of side effects that they're differential in nature, where some patients don't seem to experience it, them at the same level. But for those who have gone off therapy, they've been pretty significant.
Micah: You know, Kai GLP ones aren't the first pharmaceuticals to go viral for something they weren't originally designed for. Even before social media, we saw drugs reinvent themselves.
Chai: Yeah, that's true. Take Adderall. It was first developed to treat narcolepsy and later conditions like A DHD, but by the early two thousands, it had gained a reputation as a study drug on college campuses.
I.
Micah: And then there's Botox originally used to treat eye muscle disorders. Now it's a household name. In the world of cosmetic treatments,
Chai: just like what we're seeing with GLP ones, these drugs ran into supply chain issues when demand surged beyond their original purpose.
Micah: Let's bring Ben Locwin back into, help us unpack what happens to demand levels when a drug goes from prescription to pop culture.
Ben Locwin: There are a lot of production challenges. I think what the issue has become is we've seen the demand and use of these GLP ones grow tremendously, and a lot of it's that word of mouth marketing on social media, but they also undoubtedly do what they promised to do. And the success in this case has meant an incredible market uptake with persistent consumer demand.
So. As with anything you can model demand with demand elasticity, more demand has meant than shrinking. Supply has meant counterfeit products, reaching the market and frightening quantities, stock out situations, lack of access for some patients, pressure on the manufacturers with regard to capacity. All those things wrapped together.
Brings us to the point of we don't have infinite capacity out in the market. So as GLP ones are enjoying this incredible rise, what is that also meaning for the existing capacity out in the market for any other treatment that might be out there? And the reality is that CDMOs and CMOs are having to use their capacity space.
Micah: CDMOs are contract development and manufacturing organizations and CMOs are contract manufacturing organizations,
Ben Locwin: in some cases, large part just for GLP ones, which means then therefore they don't have capacity for other treatments that are also needed by the market.
Chai: Could you see that? Maybe there could be a pause on the usage for cosmetic reasons and some priority for patients who are diabetic.
Ben Locwin: Yeah, that was definitely talked about. The demand has been increasing for a long time, but it really sort of came to the forefront last year and the prior year where there was a question of if these are being administered for vanity use. Predominantly, I. If that were the case, then what does this mean for the patients who really need it for diabetes, for blood sugar control?
Which then of course brings up the question of, well, is uh, a quote unquote vanity use where somebody may have obesity, which brings with it other chronic health effects. Is that a less important administration of the drug? It may be a situation where it's a less acute need than somebody who needs it for diabetes control, but there are also potentially positive health effects for people who are using it for a significant amount of weight loss.
To prioritize one side over the other has been challenging, but certainly a lot of physicians were. Trying to decide on ways to maybe get patients on alternative therapies if they were only pursuing it for weight loss. And that way there would be more availability for those who needed it for diabetes.
But you know, before that ever became a really systemic change one way or another, where sort of finding ourself in the current situation where the demand has largely been met. Almost surprisingly,
Micah: and from a regulatory standpoint, are there any particular considerations that need to be taken into account for the development and marketing of these drugs?
Ben Locwin: Yeah, for the most part, because they've proven over the years to be really relatively, very safe and also very effective at what they do, whether it's for diabetic patients, whether it's for significant weight loss, there's always the balance on the regulatory side of what's the safety versus what's the efficacy.
When looking at a new drug product in a clinical trial or post-market, you know, surveillance of the market, see what's going on. So in then millions of patients, is this still safe? Is it still effective? And this particular therapy, the GLP ones, they've been. Very safe across the board. They've been very effective at what they do because they basically mimic an inre in hormone in the human body.
It's really doing what endogenous hormones are doing that we already have, and so they tend to not. Present the level of risks that we see with certain other therapies. So the regulatory pathway has been fairly streamlined and because the market has such demand for it, you know, the regulatory process, like I said earlier, you'd think that it all happens in a bubble and there aren't a lot of extrinsic factors that are influencing that.
But you know, of course, when you're seeing news reports about GLP ones and the consumer demand and that they're doing what they're doing. Very well. That certainly has an influence on regulatory bodies.
Chai: And I know you mentioned a bit earlier that there's some market for the drugs outside of the intended use.
So let's say the black market for GLP one drugs, that it's grown. Definitely. As the demand increases, how easy is it to access these drugs outside of a prescribed regulated framework? And what are the risks for patients who do purchase them illegally?
Ben Locwin: Yeah, that's, that's a serious concern. The black market and the gray market for counterfeits of GLP ones has been huge.
Micah: If you're not familiar with the term gray market, it refers to buying medical products through unofficial channels like online pharmacies instead of recognized distributors, I.
Ben Locwin: Wherever there's outsized demand for a product or service, you're always gonna find that there's a market for counterfeiting to be a financially viable angle for nefarious agents.
The principle risks, of course, are that patients are either getting a drug, which isn't what they think it is. It's either an inert entity. Which is probably the best case, or it's something else entirely than what they thought, which brings with it additional health risks from off target effects, contamination to the counterfeit product and things of that nature.
So you don't know what you're getting. So it's either nothing or it's definitely something you don't want to be getting. But the access to black market drugs. Particularly in the GLP one space, there's been a very high level of ability to access that market. And of course, you know, that then begets its own news cycle.
And so there's been additional controls that have, have been put into place to try to mitigate that. But there's still very widely available out there. And sometimes it's very difficult to know if you have, um, the real deal or if you have a counterfeit.
Micah: And of course, the more popular and the more. In the popular imagination, a product like this is the more likely it is that somebody wants to cash in on it unethically or illegally.
Ben Locwin: Oh, exactly. There's an incredible amount of money to be made. You see a lot of counterfeit rings start up for things that are even, you know, pennies on the dollar. If they can reiterate that success over and over, and now you can imagine cases where something is thousands of dollars per dose, and all you have to do in that case is just produce a fairly relevant amount of doses and there's an incredible amount of money to be made in a market that.
Is pretty unaware that all of this stuff happens behind the scenes. So you may be trying to find some of these online and not realize what you're getting. And then these actors are just profiting off of what the consumer doesn't know to be true out there with the black market and the gray market.
Micah: It is interesting that even with the high demand supply has kept up pretty well, and that's mainly because the regulatory groundwork for creating more GLP ones was set in stone years ago.
Chai: But here's something to consider. Micah, since GLP ones are injectable, what happens to all of that plastic waste from the pins?
And what about people who just don't like needles?
Ben Locwin: At the moment, I think the sustainability angle is a big concern. So all of the single use injectors have a complexity of plastics and metal, and they're often going into landfills without a well thought out sustainability angle. I've had, I. Discussions with developers about ways to better manage the sustainability angle, but at the moment, the race is on to provide with the market demands and the sustainability piece, while not entirely unacknowledged, is maybe better described as under acknowledged.
It is posing a challenge for what does the future then look like, even the short to midterm future when a lot of this stuff is going to waste. But there's such an incredible demand that to not have that same dosing regime with that same device technology means there has to be a complete overhaul of the development pathway for what the new alternative would be, what the manufacturing process looks like.
So while that. Is being looked into. You know, it's really a follow the money situation where right now just producing for market demand is giving all the incentive the manufacturers need. And so everything else at the moment, given the hot market, is kind of taking a back burner. Yeah. And from the injectable side of things, it's kind of a funny situation because.
A lot of people report that they don't like needles. You know, that's one of the reasons why people don't like to get vaccines. And certainly the same with something like an injectable GLP one. But at the same time, that hasn't really seemed to tamp down demand, as we've seen. So there's kind of a balance there with how much patients are willing to tolerate versus what their end game is and what they need the therapy for, and at the same time.
I think there's also a stronger placebo effect that's been acknowledged in injectables versus let's say, an oral solid dose. There were some studies done where they would give patients injectable saline, for example, and their reported effects in including some side effects were much pronounced than those who were given an inert dose of a placebo from some other way, like an oral solid dose.
So there's. Sort of the powerful placebo angle that I have a more aggressive treatment being done to me, which is an injectable.
Chai: So then are there any other advantages to the oral GLP one formulations other than the method of delivery and the sustainability aspect?
Ben Locwin: Uh, those are probably the biggest aspects.
One would be access. So patients who refuse to, or you know, can't receive an injection could go the root of an oral solid dose. The sustainability piece is huge on the challenges side of the fence, developing solid formulations for peptide based drugs. Presents significant scientific challenges, mostly related to low bioavailability, so there's gastrointestinal degradation.
When you swallow an oral solid dose, there's always questions about bioavailability, which in large part you get around by doing an injection. As well as gastrointestinal side effects. There's been some research looking at permeation enhancers and developing drug delivery systems that protect the peptide itself until it reaches the optimal absorption site, and then following that first pass, metabolism in the liver also contributes to reduced bioavailability, so that.
Leads to differential dosing strategies for different people depending on how their GI tract is reacting, how their liver is reacting to metabolism of the peptide. So it's, which is why I said earlier, there have been a lot of challenges to overcome on the oral side of the market. And it's not just as simple as saying.
Well, this works. What would the dose adjustment need to be to provide this in an oral dose? There's a lot of other mechanistic to try to get around in order to make it a viable alternative, and there are some oral doses that are available. Typically, the dosing has to be higher. It's a lot more different from patient to patient in terms of what they're experiencing as an effect.
But I think those are things that are relatively easy to surmount as has been done for a lot of other oral doses too. But it just requires some careful scientific work in the development process and figure out how it's gonna be best produced and rolled out in large part to the market.
Micah: Yeah, I was gonna ask, how motivated do you think manufacturers are to move to the oral dose, and from a sustainability perspective, is that just sort of a Ben Locwineficial side effect or is that an actual motivation for finding an alternative to injectables?
I.
Ben Locwin: It's a tricky question and I'm glad you asked it. Um, the eminent statistician George EP box once observed that all models are wrong and some models are useful. And when sponsor companies are trying to figure out what's going to be next in the pipeline, whether that be a totally new drug or taking existing drugs, and in this particular case, going from an injectable to an oral solid dose.
It always begs the question, what do market projections look like in terms of uptake? But again, that's that, you know, all models are wrong and some models are useful sort of situation where you're projecting based on your best guess, where focus groups have led you or where the market is saying, I will or will not uptake this therapy.
And it's been a real challenge because there's been so much uptake with the injectables that I think to your question saying. Let's wholesale move into the oral solid dose market. It's not a situation of the uptake isn't what we thought it would be in the injectable. So this just makes sense. It's wow, the injectable side of things has been so hot.
We probably could also have a huge business in the oral side of things because patients would much more likely take a pill than. Be injected, but also the market numbers don't necessarily bear that out. So it's how do you leverage some of the financing coming in from the injectables to then fund the oral solid dose development to make that better, and in hopes that the oral solid dose will either surpass the market for the injectables or will be another weighty viable alternative.
Chai: So, aside from the oral options, what other new delivery methods are there for GLP one Drugs that are being investigated to improve convenience and sustainability? I.
Ben Locwin: Yeah, there are some other avenues being looked at. There are some dissolvables sublingual. There was talks about, you know, how can we get this peptide through in a transdermal mechanism?
At the moment, just based on access to the market, what patients are comfortable with, a lot of it is how to make the oral solid doses the best they can possibly be. To be that comparator on the market. And it really boils down to the things I mentioned before about degradation and bioavailability for sure.
And the other side of it in the future. So for novel delivery methods, a lot of it is really centering now on increasing the half life in vivo. So when you're taking these GLP one drugs, you obviously don't want it to last 15 hours, you know? And in some cases these are. Persisting the body with half lives of 156 hours or more, so.
Packaging the drug in such a way that it has longer half-life in the body is really sort of what the new novelties in the approach are focused on. So whether that's on the oral solid dose side of things, which of course, you know, it also touches on the sustainability Ben Locwinefits to society. At the same time, whether it's the injectable or the oral solid dose, and in particular the oral solid dose, how do you make sure that your new developed therapies have the longest half life that can be engineered so that patients would need to take these as less often as possible in order to derive the same Ben Locwinefit?
Micah: And what about from a storage perspective? I mean, we're looking at a lot of demand and, and with injectables, the shelf life of the doses is an issue.
Ben Locwin: It has been, especially with certain peptides, but, um, a lot of that shelf stability owing to the demand on these products has almost really been a non-issue because when stability studies are done and there's accelerated stability studies done.
It's obviously to give the longest leeway possible for people to have these shipped and stored somewhere for as long as they need. But the sponsor companies are really in a nice spot of not having so much back stock of product that they're having to scrap any of it really, because before these are getting even nearly close to expiry.
And a lot of the extended stability studies are showing that even beyond those dates, these are tending to be relatively stable, uh, and still efficacious, but the demand is such that nothing's really getting old at the moment. And that's one of those things, you know, use the Crystal Ball lookout five more years.
Is that still the case? Don't know, because then you'll have market saturation by a lot of different players, so you'll have a lot of different avenues to pursue, which means now there's not just a couple or a few key players in the market, but a lot of competition, which means that there's more back stock.
So that's gonna lead the developers also to try to come up with nuanced ways of saying. Alright, so maybe these things aren't persisting on a shelf for three months or six months. What about the cases where it's 18 months, two years, three years? What do we have to say about that?
Chai: Throughout history, some drugs have transitioned from injectable forms. To ingestible ones, a good example is Narcan, which helps people who've overdosed on opioids these days. Narcan is also available as a nasal spray and can be bought over the counter.
Micah: The pharmaceutical industry has also been exploring an oral version of insulin, though we're not quite there yet.
And speaking of the future, what about GLP ones? What else could they be capable of?
Ben Locwin: So it seems to be that based on large scale population data, that there's the potential to have GLP ones effective for chronic kidney disease, for some liver conditions, for certain cardiac diseases. So those new indications are.
Being diligently pursued now. So then there's a way to treat potentially other conditions with the same drug, where the regulatory pathway, of course, then is very clear, very streamlined, and really easy to navigate. What also has been noted is that when patients are losing a tremendous amount of weight due to GLP ones, let's say they're on 'em for weight loss, but it could also be for diabetes, the the diabetic patients.
Same way. You know, the first patient was injected with insulin in 1922. It came to market in 1923. So we're talking about 102 years now that patients have been using insulin for diabetes without insulin. It was essentially a death sentence. Now we're at the point where there's a lot of different ways to modulate and mediate diabetic conditions, but what we found is that in.
Shedding significant, some significant amounts of weight through GLP ones. Patients are also losing a lot of lean tissue. So kind of this hard earned, supportive, skeletal, muscular tissue that we have that all indications when you look at senescent and geriatric populations are the more people strength train.
They stay as strong as possible for their age, and what we don't want to see is a lot of people losing amazing amounts of weight, but then losing their muscle mass with it. So one of the probably strongest things for further refinement that I see on the market is preserving lean tissue at the same time as shedding body fat.
And that's being proposed and tested in a number of ways. One of them is through modulating something called myostatin in the body. So as your body's. Shedding weight on GLP one therapy. There's also another molecule in the therapy that's helping you to not degrade lean muscle tissue at the same time, so you're kind of rebalancing things out more of what you're losing.
I. Besides body water is fat tissue, and at the same time, maybe you're not gaining more lean tissue, but at least you're not losing it at the same rapid rate as you were previously. So I think getting to the point where we can differentially affect the amount of fat loss compared to muscle tissue loss, that's really gonna be hugely impactful for the health of the large scale population in the future with something like these therapies.
Chai: So in summary, would you say that there are many Ben Locwinefits to the popularity of GLP one?
Ben Locwin: Yeah, I think for the people who take them and love them, they definitely have loved them. There are also influencers who say, you know, I tried whatever. I tried my oh Ozempic and it was the worst thing I ever did. Um, it's hard to.
Kind of divine the truth out of it, other than to say all patients are different. Not everything works the same for all patients. Uh, maybe some people are more sensitive to side effects or they have more pronounced side effects. That being what it is, there's certainly a lot of. Potential avenues to pursue.
And I think the future with these types of therapies is a strong one because there's so much market demand, so much money. That means that money goes into funding what the next generation will look like. I mean, it's always great to have that nice new lead on where science should be taking us. But those new threads.
Can never get pursued unless there's finance behind them.
Micah: We've come to our last question for you. We always like to ask our guests for a piece of advice for our listeners, and so Ben Locwin, I'd like to ask you from your perspective, what advice would you give to someone who would be interested in entering the pharmaceutical industry specifically?
Ben Locwin: Great question. You know, the famous physicist, Neils bore also about a hundred years ago, said, prediction is difficult, especially about the future.
So I think when we talk about balancing the future, it's interesting because the future never comes to us in the timing or in the form that we expect otherwise. We'd be fortune tellers. We'd all be out of a job, I guess. But having the best and brightest. Out there, you know, maybe they're in school now or maybe they haven't even entered school yet.
But having those future best and the brightest pursuing careers in the pharmaceutical and healthcare industries ensures that fruitful pathways continue to be advanced and that future patients don't have to suffer the diseases that have been a part of humanity since. The dawn of time or maybe newer diseases that come up because of the industrial era and.
I think we all are currently, or we all will be patients of the future. So I think for those who are interested in the future of healthcare for all of our societies, I would always encourage, like I said, the best and the brightest, pursue a career and realize that they'll be the new face of the future for things that we didn't even know to ask about yet.
Fantastic.
Micah: Ben Locwin, thanks so much for your time. It was a pleasure talking with you.
Chai: Thank you very much. It was really great conversation.
Micah: Thank you both.
We've been speaking with Ben Locwin Lockman, chief Scientist and head of clinical services at Black Diamond Networks. So Kai, what were some of your key takeaways from this conversation?
Chai: The history of drugs. It's really fascinating because sometimes a drug can be created and then years later it becomes famous for a totally different use.
Micah: Yeah, and it raises this interesting question of where to put the priority. There are limited supplies or supply chain issues around drug demand, and so is it morally? Ideal if, if somebody, for instance, is using GLP ones for purely cosmetic purposes, and in the meantime somebody who needs it for diabetes treatment or perhaps for non-cosmetic weight loss treatment has more difficulty gaining access to it.
Chai: Of course, when you have such a massive supply, a massive amount of product being used there is the waste issue, and with GLP ones and, and many other drugs, you have to figure out how to sustainably process the products they're packaged in. So with it being an injectable, it does raise a lot of questions about the future of the waste.
Micah: Absolutely. But of course, as we learned, at the same time, there might be progress on the front of making it an ingestible. And I think these kinds of developments in how we take the drugs and of course future uses that perhaps we don't even fully grasp yet, like the possibility of using GLP ones for kidney or cardiac conditions.
Chai: Yeah, you're so right. It's really fascinating to see where the future treatments will go and really what happens next with this drug and with many others.
This has been balancing the future from METTLER TOLEDO.
Micah: What questions about science and technology do you want answered in a future episode?
Chai: Let us know by leaving a review or if you're a Spotify user. Leave us a message in the comments section
Micah: and be sure to subscribe wherever you get your podcasts.
Chai: We'll be back in two weeks with our next episode. See you then.
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