A brief introduction:
A few months ago, I was browsing the “Trillion Dollar Public Company” club. Most of the names on the list were relatively unsurprising. The 2018–2021 (mostly) tech platform era was the first major wave: Apple, Amazon, Microsoft, Aramco, Alphabet, Meta, Tesla. 2023–2024 brought the second AI-driven wave: Nvidia, TSMC, Berkshire, and Broadcom.
But then in 2025, something changed. The first healthcare company ever crossed $1 trillion in market cap: Eli Lilly.
For a healthcare drug to drive billions in revenue, and perhaps trillions in perceived value in just a few years, the penetration rate has to reach levels unlike anything we have seen in decades.
Indeed, GLP-1s (glucagon-like peptide-1) are the insulin of this generation in a lot of ways. We’ve seen a rise in DTC companies expanding their business lines to meet the surge in demand. And we have seen just as many lawsuits by pharma companies against compounding GLP-1s, with the FDA also releasing a warning letter last month.
Does the market keep expanding? Who are the major players that are well-positioned? Does obesity eventually reach negligible levels? And will those who are over the age of 40 y.o. micro-dose GLP-1s for the rest of their lives?
GLP-1s are the first breakthrough drug in humanity’s quest for longevity in the 21st Century. While that statement seems positive on the surface, what Drew on our investment team writes below may surprise you in a lot of ways. I don’t necessarily agree with all of it, but I think it raises some pertinent questions that we all need to consider in our quest for healthy living.
—Megan
The Peptide Paradox: Why Miracle Drugs Might Be Making Us Weaker
By Drew Maloney
Two years ago, if you mentioned “peptides” at a dinner party, you’d get blank stares. Today, your grandmother has an opinion on Ozempic, your partner’s friend is microdosing BPC-157 for tendon repair, and Novo Nordisk’s market cap briefly exceeded Denmark’s GDP. During this year’s Super Bowl, if the commercial wasn’t about AI, it was about GLP-1 weight-loss drugs. The GLP-1 weight loss revolution has turned peptide therapeutics from a niche pharmaceutical category into a $50+ billion cultural phenomenon projected to grow at a 13% CAGR and reach $200Bn in 10 years. (1)
But there’s a parallel truth: we’re running a massive uncontrolled experiment on human behavior, and the early returns are concerning.
GLP-1 receptor agonists like Ozempic and Wegovy were supposed to solve obesity, a genuine public health crisis affecting 42% of American adults. The pitch was elegant: these peptides mimic a natural hormone that regulates appetite and blood sugar. Take a weekly injection, lose 15-20% of your body weight, and reduce cardiovascular risk. It’s not a diet. It’s not willpower. It’s biochemistry.
And it worked. Clinical trials showed dramatic weight loss. Patients with Type 2 diabetes saw improved glucose control. The FDA approved. Insurance companies (reluctantly) started covering it. Eli Lilly’s market cap was under $200b before GLP-1s and crossed $1 trillion in 2025, making it the first healthcare company in the world to cross that threshold. A 2025 gallup poll showed the obesity rate declining for the first time in over a decade.
Then the second-order effects started appearing.
The Muscle Problem Nobody Wants to Discuss
People on GLP-1s lose weight, but clinical data shows that a significant portion of that weight is muscle mass, not just fat. (2) In my Saturday morning workout class, in a gym on the Upper East Side where the class is overwhelmingly 55+ year old women, the instructor preaches the importance of muscle mass and why being ‘stronger’ (name of the class) is the most important thing to living the most productive life as you get into your 70s. Studies show that 25-40% of weight lost on these drugs is lean body mass—the metabolically active tissue that actually matters for long-term health.
Why? Because GLP-1s work primarily by making you eat less. Dramatically less. Patients report forgetting to eat, feeling full after a few bites, and losing interest in food entirely. When you’re in severe caloric deficit without resistance training and adequate protein intake, your body cannibalizes muscle along with fat.
The rational response would be: “Great, now we know the only downside of GLP-1s, so we should prescribe the drug AND a strength training program.” But what’s actually happening is people are choosing the injection over the gym. Why spend an hour doing squats three times a week when you can lose weight while sitting on the couch? The drug has effectively removed the forcing function that made people exercise. From someone who is trying to make changes to my body through the gym, if I could take a shot or pill to get the results I want, I would not eat and drink less, and not spend hours a week at the gym.
I’ve seen this personally. Friends who used to train regularly stopped going to the gym after starting semaglutide. “I’m losing weight anyway,” they shrug. “As long as I look good on my wedding day”. They look thinner. They’re also weaker, more fatigued, and setting themselves up for metabolic disaster when they eventually go off the medication.
We’re creating a generation of people who are thin but metabolically fragile—the opposite of what longevity research tells us we should optimize for.
The Gray Market Is the Real Story
While doctors debate appropriate GLP-1 prescribing guidelines, an entire shadow economy has emerged. Peptide clinics offering “research compounds” and “wellness optimization.” Telegram channels selling bacteriostatic water and lyophilized vials. Your trainer’s friend who can get you “pharma-grade” tirzepatide at a fraction of the retail cost.
The FDA has approved exactly four GLP-1s for weight loss. The internet offers dozens of variants: research peptides, compounded versions, Chinese-manufactured generics, “bespoke blends” from anti-aging clinics operating in regulatory gray zones. These variants from China alone have doubled YoY to $328M.
And people are injecting them. Not because they’re obese or diabetic, but because they want to lose 10 pounds for a wedding. Because they saw before-and-after photos on Instagram. Because everyone else is doing it.
A few things are happening, and the FDA is in the middle of it. The FDA has tightened rules around peptides by ending years of regulatory tolerance that has allowed compounding pharmacies to bypass traditional approval routes, seeking to have the same rigorous standards as traditional pharma.(3) But by tightening standards, they have precipitated adverse effects. The FDA felt there were not enough large-scale clinical trials. The people who are now purchasing the “gray” are often the large-scale clinical trial. These drugs are labeled “For Research Use Only” (RUO) or “Not for Human Consumption”. This labeling serves as a legal loophole that allows manufacturers to bypass FDA approval for human safety, shifting all liability and risk onto the consumer. Commercials show celebrities with notable weight loss, telling the country how easy it is to obtain GLP-1 products online. Ads mention a new pill-based version of the medication, which expands available options beyond subcutaneous injections.
Telehealth companies aren’t subject to the same set of rules and regulations regarding drug advertising as pharmaceutical manufacturers. So, as a viewer, you don’t hear a list of side effects nor do you hear the complete risk-benefit story.
Then there is big pharma’s influence. Some believe pharmaceutical companies have pushed for peptide bans to control the market and direct consumers toward patented medications.
We’re running a global experiment with millions of participants and zero longitudinal data and while the user believes they are the benefactor because they can get into a dress they wore in college, my point of view is that they are being taken advantage of by big pharma and are unaware of the long-term risks of these drugs.
The Fallout
So what happens when people stop taking these drugs?
Early data is not encouraging. Most patients regain significant weight within 12 months of discontinuation. Some studies show a rebound that exceeds the initial weight loss.(4) Why? Because the drug didn’t change behavior—it just suppressed appetite. Patients never learned to build sustainable eating habits. They never developed the muscle mass that would increase their metabolic rate. They just got very good at not being hungry while injecting semaglutide.
Now multiply this across millions of people. We’re creating a generation dependent on weekly injections to maintain weight loss, with no clear off-ramp. Insurance companies are starting to balk at covering these drugs indefinitely (at $1,000-$1,500 per month). So what happens when coverage ends? When the compounding pharmacies get shut down? When the patent cliffs hit and we discover that biosimilar peptides don’t work quite the same way?
We’re building a time bomb.
Exercise used to be the only scientifically validated intervention for both weight loss and longevity. It required time, discomfort, consistency, and delayed gratification. It built discipline. It had positive spillover effects—better sleep, improved mood, increased confidence, and community.
Peptides offer a shortcut. And shortcuts change incentive structures.
Why would a 31 year-old invest in building a sustainable fitness habit when they can just inject their way to thinness? Why would a 65 year-old do the hard work of metabolic health when a peptide can artificially improve their biomarkers? The rational economic actor chooses the injection every time.
While it may not sound like it, I’m not saying that peptides are bad. They have been life-changing for many, particularly those with severe obesity and Type 2 diabetes. Similar to social media, technology, AI, etc., if we irresponsibly use peptides, the effects on society will be more negative than the benefits that were intended. Consumers deserve to know what they are putting in their bodies, and while companies aren’t lying to consumers, they aren’t telling them the truth either.
The Peptide Bull Case
I’ve made my concerns clear. But intellectual honesty requires me to steelman the other side, because the counterarguments are not trivial.
Start with the dependency critique. I said we’re building a generation hooked on weekly injections with no clear off-ramp. I would imagine a cardiologist would push back on my arguments by saying 55 million Americans take antihypertensive medications every day. Over 700 million prescriptions for blood pressure drugs are filled annually in the United States (5), and essentially no one frames this as a societal catastrophe. The horror scenario I described — patent cliffs, biosimilars, coverage gaps — is literally just the normal lifecycle of pharmaceutical innovation, and it has historically resolved in patients’ favor, not against them.
The insurance math is also more complicated than I implied. Yes, insurers are balking at $1,000/month GLP-1 bills today. But estimated annual national health care expenditures associated with hypertension alone were about $219 billion in the United States in 2019 (6) — a condition heavily driven by obesity. In the landmark SELECT trial, GLP-1s reduced the risk of cardiovascular death, nonfatal heart attack, or nonfatal stroke by 20% in patients with preexisting cardiovascular disease.(7) Recent employer data is even more striking: female GLP-1 users experienced a 47% reduction in hospitalizations for major cardiovascular events, and approximately 50% lower incidence of ovarian cancer compared to non-users.(8) If even a fraction of those downstream costs gets avoided, the unit economics look very different in year ten than they do today.
The most compelling bull case for GLP-1s is that researchers keep finding unexpected benefits in places no one anticipated. Early data suggests GLP-1s may reduce risks related to addiction, cognitive decline, and certain cancers. We may be looking at a drug class that turns out to treat obesity the same way statins treat cholesterol, not as a crutch, but as a legitimate biological correction for a system running out of spec in a modern food environment designed to overwhelm it.
It is difficult when we engineered a food system that broke human appetite regulation at scale, flooded it with ultra-processed calories, removed physical labor from most jobs, and then acted surprised when 42% of the population became obese. Blaming people for choosing a shot over the gym is understandable when the deck was already stacked against them by fifty years of agricultural policy, food industry lobbying, and sedentary infrastructure.
The cardiovascular data is real. The weight loss is real. The potential to diffuse a genuine obesity crisis is real. I’m not dismissing any of it. But we are prescribing these drugs at a scale and speed that has outrun our understanding of what they actually do to the human body over decades, not months. The muscle loss is real and underreported. The gray market is growing and unregulated. The rebound when people stop is, by the data, nearly universal. And the behavioral habits that would have protected people long-term, the ones that required discomfort and consistency and showed up in better sleep, stronger bones, and a longer healthspan, are being quietly traded away for a weekly injection and a smaller dress size. GLP-1s may be one of the great medical advances of our generation. But right now, we are handing millions of people a powerful tool with a one-sided instruction manual. The side effects aren’t fine print. They’re the story. And until pharmaceutical companies, telehealth platforms, and the FDA start telling that story with the same urgency they use to sell the miracle, we are not having an honest conversation about what we are putting into our bodies, and what we might be giving up in return.
Sources
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Grand View Research, “GLP-1 Receptor Agonist Market”
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Peptide Drug Summit, “New FDA Rules are Reshaping the Peptide Industry”
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The BMJ, “Weight regain after cessation of medication for weight management: systematic review and meta-analysis”
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Aon Research, “Aon’s Latest GLP-1 Research Reveals Long-Term Employer Cost Savings and Significant Reductions in Cancer Risk for Women”