When you hear about treatments for weight loss or obesity in 2025, your mind may naturally go to GLP-1s.

The drugs have been a mainstay in popular culture since bursting onto the scene in earnest in 2022.

Much has been discussed about their ability to prompt weight loss or the just recently resolved scarcity issues or the access and affordability concerns of the treatments.

However, one under-discussed aspect of the GLP-1 revolution is whether a chronic disease like obesity can only be addressed by a chronic treatment like these drugs.

Enter Fractyl Health.

Despite a recent pivot from a focus on treating Type 2 diabetes to researching obesity and people on GLP-1s – coupled with a 17% workforce reduction to extend its cash pipeline into next year – the company believes its outpatient, intestinal-relining procedure can have a profound impact in the world of weight loss.

Earlier this month, Fractyl announced positive early data from its ongoing REMAIN-1 pivotal study, suggesting that its novel Revita approach to targeting gut dysfunction may help prevent weight regain after patients stop GLP-1 drugs.

On this week’s episode, Pharma Editor Lecia Bushak speaks with Fractyl Health CEO Harith Rajagopolan about the company’s prospects in the weight loss space, the recent developments in the GLP-1 arms race and how this will impact marketing around these disease states in the future.

And for our Trends segment, we’re continuing the GLP-1 focus with an update on how Eli Lilly is overtaking Novo Nordisk in the diabetes and obesity treatment market.

I’m managing editor Jack O’Brien and this is the MMNM podcast.

Hi Harith, great to have you here. So nice to be here. Thank you. So Fractal just released new data from your ongoing Remain One pivotal study and Ravita earlier this month, and I want to get into that, but first, could you just briefly explain to our audience Fractl Health’s pitch of targeting the root causes of obesity and type 2 diabetes and how Ravita works with that? Sure.

Fractl Health is focused on a singular goal for patients, which is how do you help prevent and reverse obesity and associated metabolic disease. We’ve been talking a lot about obesity in the recent past because of the success of drugs like Ozempic.

But one of the things that we also know is that while these drugs do a fantastic job of controlling weight and other aspects of metabolic disease, while you are on them, they’re not actually disease modifying therapies because once you stop taking these drugs, the effects go away.

And so, what do you need to do in order to be able to offer patients a durable metabolic reset, something that’s going to fix the thing that’s going wrong in the body, that’s causing them to have obesity, and metabolic disease in the first place. Well, you’ll know you have something like that when you find that patients have sustained metabolic benefit, sustained weight maintenance even in the absence of ongoing therapy.

So we are developing therapies that target root causes because they change the underlying physiology in the body and allow people to achieve sustained benefit, which is where we think the unmet need has now shifted in obesity and metabolic disease.

So Revita is an outpatient endoscopic procedural therapy that’s enabled by a device and a procedure that we have developed targeting the hunger center of the gut called the duodenum. It’s the first part of the small intestine.

It’s the area right after the stomach where food is first absorbed into the body and it is an area where science has shown that chronic exposure to high-fat and high-sugar diets cause changes that drive people to become obese and diabetic.

And so what Rivita aims to do is to target that region of the gut to remove the pathological lining of the gut in the duodenum and then allow the body to regenerate a healthy new lining in its place. That’s how Rivita works. Yeah, I think it’s important to note that Rivita is different from GLP-1s than that, it is a procedure technically, and it’s a medical device that kind of fosters this procedure.

And it received FDA breakthrough device designation for weight maintenance in patients with obesity who discontinued GLP-1 drugs. Tell me a little bit about the new data that was released this month and what it tells about Revvita’s potential. Well, as you mentioned, Revvita has breakthrough device designation in the United States. It’s in a pivotal trial called REMAIN-1. And that pivotal trial aims to test whether Rivita can help people maintain body weight loss after stopping GLP-1 drugs.

And in parallel to the REMAIN-1 pivotal study, which is a randomized double-blind and placebo-controlled study. We’re running an open-label study called Reveal 1. And in Reveal 1, we are taking patients who’ve already lost body weight on either semaglutide or trizepeptide and need to stop a GLP-1 for one reason or another.

And then allowing them to stop the drug, perform the Rivita intervention, and then follow these patients to see if Rivita can enable these people to be able to keep the weight off even after they stop the drug. So a couple of interesting things. Why are people stopping GLP-1s? First of all, we know it’s very frequent. More than 50% of people stop taking GLP-1 drugs within the very first year of its prescription.

And seven out of eight patients who stop GLP-1s regain almost all of their body weight back within the following year. So a lot of people are stopping it and most of the people who stop don’t achieve sustained weight loss. So, weight maintenance has become the new unmet need in obesity. That’s what Rivita is looking at with the Reveal and the Remain studies.

And what we observed in Reveal is that people are stopping GLP-1s for a variety of reasons. But it breaks down to four main reasons. Number one, they’re experiencing side effects. And the nausea or the vomiting that they have for a couple of days after the injection is just something that they can’t live with any longer. Second, they’re concerned about muscle mass loss. They have lost all of their body weight.

They have they now sustained a plateau at a lower body weight, but they’re finding it stressful to imagine how to regain muscle mass strength while on the drug. A third reason that people are stopping is because they’re worried about whether they can continue to get access to these drugs because their insurance is changing, the formulary is changing.

And so there’s something about the whole need to be on these drugs for the rest of their lives, which means the provider has to keep prescribing it and the payer has to keep covering it and all of that complexity that causes people to stop. And the fourth reason people want to stop is because it’s yet another medicine that they want to they have to take. They’ve achieved their body weight loss.

They’re already now at this new plateau and now they’re being told you have to keep taking this drug but you’re not going to see any ongoing further other weight loss. This is what you need just to keep what you have. And at that point, patients get frustrated and they say, “Why do I have to stay on this medicine just to keep this weight for the rest of my life? Why can’t I do it without the medicine?” And that’s where Rivita is proving to be interesting to patients for any of those four reasons. Absolutely.

I’m glad that you highlighted those those obstacles and kind of the factors that go into those really high discontinuation rates. Um I’ve also heard a lot of people in the industry talk about price and access being a big problem.

And companies like yours are basically trying to view this as a commercial opportunity in the sense that we can develop products or programs, even just weight loss guidance apps to help people stay on GLP-1 drugs and kind of keep the weight off in the long run, because that’s one of the biggest obstacles in the obesity space right now. You also have another product in your pipeline called Rejuva, which is a one-time gene therapy platform. Can you tell me about that and how it works?

Yeah, we’re developing a smart GLP-1 gene therapy. And as you know, GLP-1 is a hormone that exists in all of us and it not only helps regulate blood sugar, but also regulates body weight in all of us. And the way that GLP-1 works in our body that’s produced primarily by the cells of the gut and the levels go up after a meal and then the levels come back down again. And so our GLP-1 is on demand.

It’s basically released when the body needs it and then the levels go back down again when the body doesn’t. When we give drugs like Ozempic, what we’re doing is we’re giving an injectable that has very high levels for a sustained period of time, which is a different type of a profile than the GLP-1 within our body.

What we’ve done is we’ve developed a way to make the pancreas produce human GLP-1 in a way that mimics the normal GLP-1 in each of us, where the levels rise on demand and then come back down again when not needed. And we’ve been testing this in preclinical models, models of diabetes, models of obesity, and we’ve done them in head-to-head studies against semaglutide, which is in Ozempic and Wygovi.

And what we’ve seen is that the Rejuva smart GLP-1 gene therapy has a potential to have more potency than asymglitis alone and greater durability of effect and perhaps best of all, it’s a one-time treatment that can have potentially lifelong benefit.

And so, what we see is the opportunity to take all of the great things that we’ve learned about treating with GLP-1s and figure out a way to deliver in a manner that doesn’t require lifelong benefit, lifelong therapy. Again, with the view towards offering people sustained benefits on weight and blood sugar and other metabolic effects without the need for ongoing medical therapy. Absolutely.

And you know when people think about weight loss currently, a lot of people immediately think about Ozempic and we go being kind of those household names that became very popular thanks to social media and celebrities, but the reality is on the ground floor in the farm industry. A lot of companies like yours are using GLP-1s as a foundation to basically develop more personalized and targeted therapies therapies that might be more longer lasting.

The the obesity Obesity market is is fracturing. It’s not just about GLP-1s necessarily anymore. So how do you see the obesity landscape in the future? Where do you see it going and where will the opportunities lie for companies to kind of dive in beyond GLP-1s? Well, I think that you’re right to say that I think we’re in the very, very first innings of the obesity market.

And I with a disease that affects 100 million Americans, I think you have to first start by saying that none of the drugs that we’re using today are actually going to reduce the number of people with obesity. They’re all going to provide tools to manage it, but the number of people with obesity is likely to continue to grow. And so one way to think about the obesity market is how are all of the different ways to think about managing the disease.

And then another way to think about it is what are all of the ways to think about reversing the disease or preventing it altogether. to reduce the number of people with obesity. So I put them into three biggest buckets. Number one, medicines that are used to manage the disease on an ongoing basis, which can help alleviate symptoms, but aren’t going to reduce the number of people with obesity in the world.

Number two, diet and lifestyle interventions that can effectively prevent obesity if you adopt it early enough in your life and can be used to manage obesity when you have it, but if you stop the lifestyle, the obesity’s going to come right back again, just like with GLP-1 drugs. And then the third category are ways to try to reverse the disease by changing the body’s physiology.

And the way that’s existed for 30, 40 years is bariatric surgery and now new approaches like ours with both Rivita and Rejuva to offer more scalable ways of achieving the same thing, which is to be able to fundamentally fix the physiology so that the body can regulate body weight on its own. Now, within the pharmacological class, which is growing because of GLP-1s, right? There’s things that can offer different ways of dosing from injectables to orals.

There’s things that can offer more potency. There are new mechanisms and there are things that have longer-lasting effects. And so there’s a ton of innovation happening in that category, but it’s important to contextualize that the innovation there is still all in the name of managing a disease that is going to need on ongoing therapy for a growing number of people, rather than actually treating the disease directly.

And I wanted to throw in a question about obesity marketing for our listeners of marketers. Um and you know how can car companies like yours use marketing and communications to sort of carve out a name for themselves, carve out your own path in this noisy obesity space as it continues to grow and you know more players join.

Um you know obviously you don’t have uh a product necessarily to market currently in the market, but I’m curious what you’re thinking about on on the marketing and communication side in terms of defining who you are amid this this larger growing market. I love this question.

I think that marketing products like the ones that we develop ultimately starts with really understanding what is the need in the in the customer today, right? And despite the amazing popularity of the drugs that have been recently developed, there are still really substantial needs.

And so to my mind, the fundamental question is, how does your product that you’re marketing offer through differentiation for those needs? And I think that like the challenge and the opportunity in front of marketers is to be very crisp about what that differentiation actually is and then to make that crystal clear.

In our world with both Rivita and Rojuva, our differentiation is a durable metabolic reset. Metabolic benefit without ongoing therapy. That is the differentiation. That is where we think the largest unmet need is. But as I mentioned, there’s lots of unmet needs, but you just have to be very clear on what your differentiation is.

And what I like about what we’re doing is it offers patients a pathway to an off ramp from medicines, a opportunity to offer people the ability to lead a healthier life free of ongoing medical therapy. Which which I think is a tremendously desired but totally unmet need and obesity today. Absolutely.

And as you’ve kind of touched on this conversation, there there’s still a lot of unmet need in in many ways and each patient is very individual as well. And I think um as the market grows um obesity treatment and diabetes treatment is going to become more personalized as well. And I think there there’s something to be said for that in marketing.

Um looking ahead to the future, what is one thing that you hope to see change in the pharma industry when it comes to the obesity space? I think the pharma industry has become a slave to evidence-based medicine and clinical trial data. And what that means is that you see incredible results in clinical trial data that are not bearing out in the real world experience with these drugs.

And somehow everyone ignores all of that and then just focuses on what they see in the clinical trial data. So, in the real world, if you’re taking a GLP-1, titration is time-consuming and hard. Access is a challenge. Side effects are real. The desire to stop therapy is legitimate and frequent.

You don’t see any of that stuff in a clinical trial where you have 95 plus percent adherence for three or four years and you’re able to show benefits like cardiovascular risk reduction or prevention of diabetes and then you flip the script and you look at the real world and most people are stopping the drug long before they have any benefit. And yet the pharma industry continues to be very focused on what are the clinical trials show rather than how is that pulling through to the real world. And that’s one thing that I would change tremendously.

The balance of evidence generation and value needs to shift more towards what is actually delivering in the real world, rather than what can one prove scientifically in a clinical study. What are the next steps for Fractal and your products? Are there any new initiatives on the horizon that year are excited about. Yeah, I mean 2025 is going to be a year of acceleration and execution for Fractl across both Rivita and Rejuva.

And we’re super excited about upcoming catalysts and milestones across both programs. With Rivita, we’ve got more open label data coming from the weight maintenance Reveal 1 study in Q2, and then a key randomized data set coming in Q3 from the Remain 1 pivotal study. We anticipate completing enrollment in the full pivotal trial this summer and pivotal data that is sufficient for potential registrational filing with Reviva in 2026.

So a weight maintenance, a non-drug weight maintenance option with key pivotal randomized data is just months away. That’s one thing we’re really excited about.

On the Rejuva gene therapy front, our smart GLP-1 Rejuva-001, the first drug candidate in the Rejuva platform, we’re on the verge of filing with regulatory in order to begin a first-in-human study, and we anticipate being able to report early data from a first-in-human study of a potentially curative gene therapy for type 2 diabetes next year.

So if you and I meet again in the summer of 2026, we’re going to be having a totally different conversation with potentially pivotal data from Rivita and weight maintenance that could be the basis for registration in the United States and a potentially curative approach to type 2 diabetes with early first-in-human human data from the gene therapy. So, acceleration and momentum and execution in the months ahead. Absolutely. That sounds like there’s a lot of exciting news on the horizon.

So, thank you so much, Harith, for providing our listeners with these insights. We’ll definitely be keeping a close eye on Fractal Health and the space as a whole as the obesity market continues to grow. So, thanks so much for joining. Thank you.

Trending. And this is the part far of the broadcast when we discuss trending healthcare headlines and it has been a huge week in the GLP-1 treatment space. Really good week if you are on the side of Eli Lilly. Not so great if you’re on the side of NovoNordisk. Lesha, do you want to give our audience a little sense of what has gone on and then we can get into a little bit of the analysis that we’ve seen from some external players, but solid week for Lilly.

Yeah, so Lilly announced this week that its oral version of its GLP-1 drug, terzopidine was effective in a Phase 3 trial, which is a big feat for the pharma company. Obviously, an oral pill version of these weight loss drugs would be pretty popular. Right now, they’re just injections.

So, both Eli Lily and NovoNordisk have been trying to move a pill version forward and Eli Lily appears to be winning the race at least for now. Um, so that was big news this week and it kind of underlines this ongoing competitive race between these two dominant obesity players and lately analysts are saying that Eli Lily overall is kind of surpassing Novo in the race.

Novo NovoNordisk was shot to popularity with Ozempic and Wagovi and it seems the growth that NovoNordisk is seeing is now slowing down a bit while Eli Lilly’s is growing faster. NovoNordisk saw a 26% increase in revenue in 2024 and Lilly saw a 32% increase in its revenue in 2024. In both cases, obviously their weight loss drugs were contributing to a lot of that growth.

And that gap growth is expected to continue this year. Lilly’s projected to grow again around 32% and Novo is expected to grow somewhere between 16 and 24%. So again kind of slowing down a bit there. And analysts at BMO Capital noted that Lilly’s Mounjaro and Zephron are the reasons behind that growing gap. The drugs are taking US share from Ozempic and Wagovi.

And this pill race that’s been introduced is just kind of intensifying that further. It’s interesting that you said that Novo had shot to popularity. I don’t know if that was a pun there, but this idea of of the injectables versus the pill. Oh yeah It’s obviously where the the focus is. And And having seen Pfizer have to pull their twice daily pill from the clinical trials that they were going through. And then just days later, you see Lilly come out there, have this really positive data.

I think on the first day that that news got announced, Lilly’s stock went up 16%. Novo went down 5%. Then you have all these, you cited the BMO analysis. There was a piece that ran the Motley Fool with the question, did Eli Lilly just say checkmate to NovoNordisk? Like the paradigm has really shifted in a meaningful way and I think it really speaks to like you said this arms raise not only for the injectables but certainly the pills. That’s really where everyone wants to be the the first mover. Right.

And Novo has been advancing its own pill version called Rebellsis which is currently already approved for diabetes. but the company is planning to submit that to the FDA for an obesity approval this year. So we’ll see what happens with that. Eli Lily, I imagine, is is racing to get theirs in as soon as possible to kind of beat Novo on that. I also think all of this points to an increasing fracturing of the obesity market.

A lot of the leaders in the obesity space that I’ve spoken to in the last six months or so have all kind of told me the same thing that Novo and Lily currently hold the top spots, but there’s going to be such a massive growing of the obesity market in the coming five years or so with more and more companies developing non-GLP-1 treatments or in other types of weight loss treatments or complementary treatments to GLP-1 drugs.

There might be new mechanisms of action that are discovered that other companies pursue. Novo and and Lily aren’t guaranteed to hold these top spots forever either. I think because they’re there is going to be such a big fracturing in the market. I think, you know, it’s expected to grow to be like a $100 billion dollar more market in the next five years. So, it’s constantly changing.

And it’s interesting too, like the the interview with uh Harith from Fractal is fascinating in terms of like basically they’re looking at saying, it doesn’t just have to be this one mindset that we have about it or it’s like it’s the injectable or it’s the pill. It’s like there has to be this much more nuanced and comprehensive approach to obesity care. And I think it’s interesting that leaders they’re saying that too, where it’s like, yeah, we have these two major players at the top, but obviously Pfizer’s been putting a lot of money in there. Roche has their their operations with CAR MITT therapeutics and everything.

So it’s like people are saying like, yeah, this is what the paradigm is right now, but two years from now, we’ve even seen how much the space has changed in the past two or three years where we could be near the end of the decade, how many people are going in the space and what that medication looks like. It’s it’s probably not going to be just what we see right now, which is kind of fascinating. Right.

I mean, I think GLP-1’s definitely created the foundation and created that paradigm shift in how we view weight loss and view obesity as a disease, but it is just the foundation and there’s going to be so much more that happens. So I think, you know, Novo and Eli Lilly, while they’re currently kind of in this arms race at the top, they both might kind of lose share a little bit as as these other treatments and therapies come up in the coming years, but it’ll be interesting to watch.

And it’s one of those things too that like as we’ve seen kind of the fallout from the COVID-19 pandemic and it’s It’s not It’s not a one-for-one thing, but like obviously Pfizer, Johnson Johnson, Moderna, they all shot up with these, you know, high revenue numbers based on selling these Yeah. COVID vaccines and then that goes away Dropped off completely And so there is a lesson learned there for Drugmaker concerns of like having a diversified portfolio. I was even looking the other day to ranking of the top 20 pharma companies and like Lilly has shot up there.

Yeah They’re they’re one of the highest ranking but they’re still not in that catalog. I mean they’re still not in that league of J&J, Amgen Right. Yeah All those other ones there. And I do want to say just to be fair to Novo too, CFRA put out a note earlier this week saying that they had cut their target price from $88 to $64 for Novo and this was talking about the increased concern about their long-term competitive edge, which I think you were alluding to there.

But they said it will still remain one of the market leaders and I think that’s that’s something that both they and Lily share in terms of having that first mover advantage, but they did talk about this concern with the CAGR EMA data that came out at the end of last year, the fact that Lily could continue to surpass them, that somebody else could come up there. So it’s a mixed bag, I think, at best for Novo, but it kind of speaks to this changing dynamic we’re seeing in the market. For sure, yeah. Anything else that you want to highlight there? I think it’s been a pretty good conversation and it was a great interview too.

I really enjoyed getting to listen to it. No, I mean I think I’ll be watching both Novo and Elilly as they seek to submit their pill versions of the drugs and we’ll see how much that changes patient adherence and and really just the treatment of obesity. I think a pill would make a big difference in how it’s treated as well and just in terms of convenience for patients and you know it might increase their adherence to the drug you know obviously There’s a lot of side effects associated with GLP-1s.

I’m curious how the pill would differ from the injection in that. Yeah, it was interesting to see them say that kind of the safety profile is similar in terms of you know having those intestinal issues or vomiting and nausea stuff like that. But your point is well taken in terms of whether patients be more likely to take it or whether they can just make more of it. The reason that we had all the scarce issues is it was hard to make those pens but if you can start popping them out like pills, that’s going to be a lot of easier for them.

So definitely a situation I’ll be watching very intently and I’m glad that we’re able to dedicate the entire episode really to this burgeoning space that continues to fascinate us on a week-to-week basis. Thanks for joining us on this week’s episode of the MMNM podcast. Be sure to listen to next week’s episode when we’ll be joined by Publius Health Media CEO Andrea Palmer to preview the upcoming Health Front conference. Take care everyone.

The MMNM podcast is produced by Bill Fitzpatrick Gordon Feller, Lesha Bushek, Ira Rickraj, and Jack O’Brien. Great review and follow every episode wherever you listen to podcasts. And be sure to check out our website mmmmm-online.com for the top news stories on the pharmaceutical industry and medical marketing agencies.