Weight Loss? We’re Betting on a World Where People Don’t Gain Weight in the First Place

By Peter Kolchinsky, PhD

When we profile a portfolio company, it’s because we are moved to share something about its vision and technology that we think might have an outsized impact on the world, creating societal value beyond what most people imagine. RA Capital is an investor in Terrestrial Bio, and I’m on the company’s board. What inspires us, management, and other backers about Terrestrial is that it offers the most direct path to a world of weight-gain prevention that gets overlooked in the current frenzy to develop more powerful weight-loss agents. I hope it inspires you, too. 

Think about someone you know who, a couple of years ago, quietly got into better shape. Not dramatically. They didn’t run a marathon or go on the latest miracle diet. They just stopped looking like they were losing the slow battle with weight that most of us lose as we age. If you asked them about it, they might have deflected, or maybe they mentioned they were on a GLP‑1. Really? A medication? They weren’t sick. No. But they decided they didn’t want to keep struggling so hard to stay at a healthy weight.

That person is everywhere now. That person is the market.

The dominant conversation in GLP‑1 development is currently about weight loss. It’s about patients who need to shed fifty or a hundred pounds, the race to develop more potent peptides, the combination regimens for people who can’t reach target weight with semaglutide or tirzepatide alone. That conversation is legitimate and the market it describes is real. But it is a conversation about treatment. The conversation about prevention – about the far larger population of people who are not yet obese or overweight and would prefer never to become so – is only just beginning. Most of the industry hasn’t joined it yet, but it’s getting there.

Terrestrial is our bet on prevention becoming the dominant conversation. And as you’ll see, South Park got there first.

What Terrestrial Has Invented

Terrestrial has developed an epi-intradermal microneedle patch for semaglutide delivery. That’s a mouthful but it’s actually pretty simple. Once a week you apply a round patch to your skin – on a Sunday before brushing your teeth, say – like a child’s temporary tattoo of SpongeBob. You leave it there for a couple of minutes, then peel it off and throw it away. No refrigeration. No sharps container. It’s easy.

Unlike other more common patch technologies that use microneedles to inject a liquid under the skin or that coat the surface of metallic needles with drug, Terrestrial’s microneedles are themselves made from the drug. They are engineered to be strong enough to penetrate the skin to ensure the right dose is delivered, and stable enough at room temperature to survive the whole supply chain. The base of each needle is designed to dissolve at just the right rate to let the needle detach under the skin after a few minutes of application. Each of those properties – the mechanical strength, the dissolution kinetics, the thermal stability – requires deep materials-science expertise and is protected by intellectual property that would be difficult to replicate or circumvent. So we do not expect dozens of intradermal competitors flooding the market. We haven’t found another company able to do what Terrestrial can do. 

However, when a person is looking for a needle-free GLP‑1 option, they will also consider oral pills, which have recently come to market. Those will eventually go generic and potentially even become over-the-counter (OTC) medicines that don’t need a prescription, like aspirin and acetaminophen. But because the market is stunningly large even at low price points, and because Terrestrial has a very low cost of goods per patch (<$2 per patch at scale), it can remain competitive down to prices where cost stops mattering and consumer preference takes over (as in the case of Bayer Aspirin vs store-brand). Our bet is that a sizable fraction of the market will want a needle-free option and prefer not to take a pill every day. For some, a once-weekly application is easier to stick with.

The company has initiated a Phase 1 study that will establish the pharmacokinetic profile of the patch. Preclinical and early clinical data suggest it tracks closely with injectable semaglutide. Once that is confirmed, the development path is well-lit: semaglutide has one of the most extensive safety and efficacy databases in modern drug development, and the regulatory science for a weight-loss indication is well understood.

Securing approval for Terrestrial’s patch in semaglutide’s current indications would unlock considerable value. But it’s only the beginning. Terrestrial plans to show that patients who have already lost weight on semaglutide can use their patch to maintain their weight. Think of this as secondary prevention since it’s preventing weight gain after someone has already gained weight once and lost it. And from there it’s hardly a big intellectual leap to use it for primary prevention – helping people avoid becoming overweight in the first place. 

The Prevention Market

South Park ran an episode a few years ago lampooning people who used Ozempic off-label to shed a few pounds they didn’t strictly need to lose because they weren’t yet overweight. It wasn’t exactly complimentary, but South Park doesn’t satirize behaviors that aren’t widespread. The show’s writers were recognizing that a large and growing population of otherwise healthy people were seeking pharmaceutical assistance to maintain a normal weight. At this point, more than a million Americans without obesity or diabetes have been prescribed a GLP‑1, many of them not yet overweight and showing no obvious medical need, often paying for the drugs out of pocket. The market is sending a clear demand signal.

Roughly 200 million Americans are currently overweight or obese. Someday, many of these people will successfully lose weight with the help of the stronger and stronger drugs the industry is racing to develop. 

Meanwhile, many people who haven’t yet become overweight are trying mightily to avoid gaining weight. Until GLP-1s came along, they were the people running diet challenges on themselves, intermittently fasting, boring their friends about keto, cutting out carbs for a month, and cycling through strategies that work until they don’t. 

Does it make any sense at all that people who are at a healthy weight should have to lose the fight against weight gain and become overweight before getting the help they need to get back to a healthy weight? That seems absurd. It makes much more sense to just help people not gain excess weight in the first place. 

It is not a disorder to want help staying at a healthy weight. Staying at a healthy weight helps us look and feel better, sure, but it also decreases cardiovascular risk and cancer risk, among other risks. And the people already doing it are simply ahead of our regulatory, medical, and commercial conventions. The science and demand are there; the products, labels, and conventions will catch up.

To help most people avoid gaining weight, we don’t need stronger drugs than what we have. Turns out it takes a much lower dose of semaglutide to quiet the hunger noise that leads people to gain weight than it takes to lose weight once a person has put it on. That bodes well for tolerability. We just need to make the existing drugs widely available in the most convenient possible forms. 

Enough people already use today’s injectable GLP-1s to avoid weight gain that the phenomenon got South Park’s attention. But reaching tens or hundreds of millions will require something better. Imagine a product with this profile: no needles, no refrigeration, no prescription needed, no requirement to take it on an empty stomach, no liver-metabolism interactions with other drugs, and, I think most importantly, an actual label for primary weight-gain prevention, thereby legitimizing GLP‑1 use for that purpose.

The Market is Very Large

Without a GLP‑1, we know that most people will at some point start to struggle to manage their weight, and most will eventually lose that battle (60% of Americans are overweight or obese). And of those who aren’t overweight, many have to work harder than they might like to diet to avoid gaining weight. So while the current focus is on helping people lose weight, it will shift over time to helping the next generation not gain it in the first place. If we assume that weight-loss products will be priced as low as $25/​month (>90% lower than GLP‑1 cash prices today), ten million consumers represents $3 billion in annual sales. One hundred million people would represent $30 billion. And beyond the US market, consider that globally 3 billion people are overweight or obese. 

I am not predicting price or market penetration but merely pointing out that the scale of this market opportunity is beyond what any drug class has conditioned us to contemplate. It helps to step out of our medical drug comfort zone and consider analogous markets.

When it comes to weight management, GLP‑1 is essentially a willpower supplement. By quieting hunger noise, it makes it easy for a person to resist overeating. Just as many people don’t think twice about reaching for an Advil when they get a headache, imagine a world in which you can just reach for an OTC product when you see your weight starting to trend up and want help getting it back down. 

Most people wouldn’t guess that Advil and other OTC pain relievers sell roughly $25 billion to $30 billion a year globally, with NSAIDs and acetaminophen each accounting for something on the order of $10 billion to $14 billion in annual sales. They’re easy to take, easy to find, and everyone has them in their medicine cabinets. Most people take them only episodically, so one bottle might last a year. Some people even buy branded versions when identical store-brand products sit on the same shelf and cost less. This shows that, below a certain price threshold, people aren’t optimizing for cost. They pay for familiarity and reliability. They have a preference for factors beyond just paying as little as possible, including brand and formulation. That’s an important observation that will come in handy later.

So if drugs that people take only occasionally support a $25 – 30 billion global category, what about a drug people take for long stretches of time or even regularly? 

Now imagine a room-temperature-stable, needle-free semaglutide product reaches a pharmacy shelf and, with no friction to access, a healthy person can decide to try it on their own to help them maintain their weight (or, of course, lose weight). Prior to GLP-1s, Americans were spending roughly $70 billion annually on weight-loss schemes: Jenny Craig, diet books, meal delivery programs. Those are paid for out of pocket and are typically not effective and yet they still found buyers. A product that actually works and is available without a prescription will find more.

For another indication of how much people are willing to spend on their appearance, note that cosmetics sell over $400 billion per year globally. And what’s interesting is that the US portion of that is only 20%. The drug industry is used to thinking about the market for a novel medicine being largely based in the US. Yet, to the extent that an OTC GLP‑1 is more like a cosmetic product, it might be more appropriate to think of the global market for that category being much larger ex-US than in the US. So we need to think more globally. Indeed, the wealthier the world gets – and it is getting wealthier – the more people struggle with an overabundance of easy calories and the more they will be open to a product that helps them tamp down on the hunger noise to prevent weight gain.

So affordable OTC weight-gain-prevention drugs should be thought of as a new consumer-health category that operates within its own distinct parameters, not merely as latecomers to the crowded GLP‑1 class whose dynamics the pharmaceutical industry thinks it understands. We’ve only begun to see this new category emerge through the off-label use of high-priced, prescription, injectable GLP-1s that South Park parodied. 

Some might rightfully ask whether the GLP‑1 class is safe enough to be available OTC. Like all medicines, GLP‑1 drugs carry warnings, and the FDA would require evidence that consumers can determine whether a product is appropriate for them and use it properly without a doctor’s supervision. I’m not going to get into the specifics of the GLP‑1 drug label, but to get a sense of how safe they are considered to be, consider how widely these drugs are now prescribed, often with only modest medical oversight. From here to OTC is a smaller step than for a medicine that is rarely prescribed and requires seeing a specialist. We have a lot of data with which to inform the real-world risks of widespread use. That can help to inform an OTC label. 

Consider also that medicines do not have to be risk-free to become available OTC. Aspirin causes GI bleeding and acetaminophen can cause liver failure, yet both are sold in every pharmacy because their benefits justify their risks when properly labeled and used, even though some people disregard those labels and increase their risk of harm. 

Especially at the lower doses likely to be sufficient to help many normal-weight people tamp down their hunger noise, we expect semaglutide’s benefit-risk profile to be favorable. FDA will require studies to prove this, which Terrestrial is preparing to run. And even if OTC status never comes, a needle-free, room-temperature-stable, weekly patch could still be highly valuable as a prescription product.

Why a Patch and Not Just a Pill

Two oral GLP-1s, semaglutide (the Wegovy pill) and orforglipron (the Foundayo pill), are already on the market and will eventually become generic and maybe even become available OTC. More oral GLP‑1 options are coming. For many people in the prevention market, a once-daily pill will be the preferred vehicle, and that market will be large. But oral GLP‑1 drugs have some downsides for the episodic, health-motivated consumer. 

In the case of oral semaglutide, you have to take it on an empty stomach with water and wait thirty minutes before eating (Foundayo does not share those restrictions). That’s inconvenient. Some of these molecules have shorter half-lives, which means that missing several days and then restarting at the same dose could cause nausea. People therefore need to choose a drug they can adhere to reliably. For example, the Foundayo label tells you to call your doctor to discuss how to restart if you’ve stopped taking it for a week. Foundayo’s label also warns about liver-metabolism-based interactions with other drugs that can produce higher or lower drug levels than one would normally expect if each drug were taken alone. Semaglutide does not have similar interactions. Foundayo is a remarkable drug, and these are manageable issues for a motivated patient, but they may be barriers for someone who is healthy, busy, and treating this as a lifestyle product rather than a disease treatment. For weight-gain prevention to reach tens or hundreds of millions of people, it’s got to be very easy to be worth it.

A once-weekly patch sidesteps most of these barriers to adoption and proper use. The half-life of semaglutide is long; a single weekly application provides sustained coverage. No food interaction to manage, no daily decision point to forget, and more forgiving if an application is a few days late.

People go on diets when their weight drifts up, stop when they reach their goal, and start again when the weight returns. Many people already use GLP-1s in much the same way: they take the drug for a few months, stop when they are comfortably back in range, and restart when their weight or hunger begins creeping up again. The difference is that instead of repeatedly summoning the willpower to overpower hunger, they use a drug that quiets the hunger noise in the first place. 

Restarting after a meaningful break may require briefly re-titrating from a lower dose, but that is simple enough once you know how. Once a person knows what GLP‑1 can do for them, as millions of Americans have already figured out, weight management becomes more predictable and less stressful. 

I can speak to this from personal experience. I have used a low-dose semaglutide for a couple of years to keep my weight within a tight range (+/- 3 lbs) that used to require considerable active effort to maintain. I don’t actually mind the injection; the needle, it turns out, is far smaller than I anticipated. After the first few weeks, I found the side effects minimal. What creates friction is everything else. Because I don’t use the drug consistently, a multi-dose pen lasts longer than a month, so I keep it in the fridge. So instead of being able to use it as part of my morning routine, I have to remember to take my shot after I’ve already started my day. I don’t travel with the pen because of the refrigeration requirement, so I miss doses when I’m away. I’ll confess that I don’t handle sharps disposal as carefully as I should, which, from what I’ve read, is a common problem. Net net, there’s a small but notable gap between my intentions and my behavior.

A box of patches in the medicine cabinet, applied before I brush my teeth and discarded when I’m done, once a week, allows for a fundamentally different and much easier routine. I would prefer it to current injectables and to a daily pill.

Our market research suggests a meaningful share of the prevention population feels similarly. Nearly all respondents preferred a patch to an injectable, and the patch held up well against daily oral pills. 

A more credible threat than a once-daily pill would be a once-weekly pill. That would be genuinely interesting, and I’ll admit it’s something I might find compelling, possibly even more so than a patch. A successful weekly pill would need to deliver reliable exposure without fasting or meal restrictions, offer an active ingredient people trust, and be manufactured economically at enormous scale.

Oral semaglutide benefits from using a familiar, well-characterized peptide, but its low and variable absorption from the gut requires patients to take it on an empty stomach and wait before eating. Consolidating a week’s exposure into a single oral dose makes that absorption challenge even harder. Developers are pursuing new absorption technologies, engineered peptides, prodrugs, long-acting small molecules and ingestible devices to overcome it. Any of these approaches may ultimately succeed. Each introduces novelty into the active molecule, its absorption or release, or the delivery device, raising additional technical, safety, and regulatory questions. Those questions will matter, particularly if the ultimate ambition is OTC use by otherwise healthy people.

Meanwhile, Terrestrial is working with the best-studied GLP‑1 peptide in history. That counts for a great deal when it comes to the speed and confidence with which a product can move toward broader access. I think lots of people will prefer tried-and-true semaglutide made more convenient over either a newer molecule that has been used in far fewer people or a pill that requires fasting or other dosing conditions.

In a market that may grow to serve billions of people around the world, even a small share translates to potentially tens of billions of dollars in global sales over the long run. And because the Terrestrial technology is quite sophisticated, we are unlikely to see a dozen generics enter upon patent expiry. Even if a few copies entered the market, there is likely to be brand loyalty, as we see with Advil and Tylenol. And because of the substantial cost to build up manufacturing capacity to serve such a massive market, competition will take a long time to ramp up capacity. All of which is to say that Terrestrial is aiming for many billions of dollars of very durable revenue. That’s a vision worth building toward.

And creating a product category that helps people avoid gaining excess weight would be profoundly valuable to society. Economists at USC estimated that Medicare coverage of effective weight-loss drugs could generate nearly $1 trillion in social benefits over its first decade while saving Medicare $175 billion to $245 billion. Their model projected reductions in diabetes, heart disease, cancer, stroke, and disability. Those estimates concern treating obesity, but preventing it in the first place would at least have the same benefits, including nearly two additional years of life expectancy, some of which could translate into longer working lives. A separate USC analysis estimates that each additional year Americans collectively delay retirement generates roughly $1 trillion in economic value annually. 

So as you think about how much we collectively might spend on GLP-1s to keep off weight, consider how much more we’ll gain.

Models should reflect that patents are not the only moat

Most drugs are valued against a clock – the thirteen or fourteen years of effective patent life that separate launch from generic competition. But Terrestrial’s asset is not primarily a drug. It is a manufacturing platform. While the cost per patch at scale is very low, building the production infrastructure to get there is capital intensive. It takes years and significant capital investment, and once built, it is not easily replicated or disrupted. We’ve already seen this dynamic play out with pre-filled pens: when Lilly and Novo couldn’t initially keep up with GLP‑1 demand, compounders stepped in, but they mostly sold vials. Eventually, Lilly and Novo added enough capacity to keep up with demand, and even when Wegovy goes generic, other companies won’t readily be able to turn on enough supply to drive the kind of price collapse that we see with pills going generic. The same logic applies here: a generic patch is not something any contract manufacturer can spin up quickly. The supply chain is the moat.

This matters for how you think about the timeline of value creation. The prevention market I’ve described is real. It may come fast or it may come slower, but it will come. And I think it will grow to be huge. People will do all they can to prevent weight gain so they never have to lose weight. Terrestrial will just make it easy.

And if it takes time for this market to reach its full potential – maybe new regulatory pathways will need to be negotiated, manufacturing built out, and consumer habits formed – that’s fine. Unlike a conventional drug racing against patent expiry, Terrestrial’s moat will be its manufacturing capability and know-how, which doesn’t expire in an instant. As the category grows, there will be competitors, so the model should include gradual margin erosion but not a typical patent cliff. Look out over decades and imagine this is like Bayer aspirin – except much bigger and likely with better margins. The company can grow into the full scale of the prevention opportunity, using profits to fund the capital expense of building capacity over a decade or two, without the clock running out on its competitive position. 

Doesn’t go generic?! Isn’t that wrong?!

Fair point to raise, given that I wrote The Great American Drug Deal and founded No Patient Left Behind on the premise that drugs should go generic without undue delay. But the biotech social contract applies to medicines reimbursed by insurance – the deal where society funds innovation through temporarily high prices via proper insurance with low out-of-pocket costs, then gets generic access so everyone saves on their premiums. That’s not the model here. I’m modeling an OTC consumer product priced at commodity levels from the start because ultimately Terrestrial will need to compete with generic orals. There’s no social contract tension when the price is already low enough that access isn’t the barrier. Consider that Bayer aspirin is branded and more expensive than store-brand generics – yet nobody’s complaining.

Longer term, the Terrestrial platform is not limited to semaglutide (or even to weight prevention). If a more potent peptide with a longer half-life emerges – one suited to a once-monthly rather than once-weekly application – Terrestrial is the natural delivery partner. The asset is the manufacturing and formulation capability, not just the current molecule.

Terrestrial is a bet on a future focused on prevention

Prevention makes more sense than treatment in every area of medicine where we’ve had the tools to practice it. We vaccinate. We prescribe statins to people who haven’t had a heart attack. We recommend blood thinners and drugs to lower blood pressure to people who haven’t had a stroke. The proposition that it is better (and more cost-effective) to avoid a disease than to manage it afterward is not controversial – it is a first principle of modern public health. Weight gain is no different, and the people already using GLP-1s episodically to manage it are not confused about their needs. They are simply ahead of the curve.

Having raised a $50 million Series C led by RA Capital earlier in 2026, Terrestrial has raced into the clinic and begun scaling the manufacturing capabilities required to serve this market. We’re proud of what this team can do for the world and excited to support Terrestrial in reaching its full potential.

Godspeed, Terrestrial.

Peter Kolchinsky is a Managing Partner at RA Capital Management and a board member of Terrestrial, in which RA Capital holds a position.