Metsera, is this for real?

Eighteen months ago, Metsera was a stealthy startup with a catchy name and a promise to bioengineer a more efficient GLP-1. Last month, Pfizer announced it is buying the company for $4.9 billion. It is a bold move for a pharma giant still recovering from its own failed oral GLP-1. Just a few weeks later, Novo Nordisk trying to outbid Pfizer with an offer valuing Metsera at roughly $6.5 billion.

Today on the newsletter, I want to unpack what is inside Metsera’s pipeline, why two of the world’s biggest drugmakers are fighting over it, and finally, my take: is Metsera for real?

Earlier this year, the global market for anti-obesity medications reached an annualized run rate of about six billion dollars. Goldman Sachs projects that by 2030, that figure could grow more than sixteen-fold to one hundred billion dollars. The driver is obvious: obesity rates have nearly tripled since 1975, according to the World Health Organization. Today, it is the fifth-leading risk factor for death worldwide, and by 2035, more than half of the global population is expected to be overweight or obese. The economics are staggering as well. In the United States alone, obesity-related medical costs totaled about one hundred seventy-three billion dollars in 2019. Globally, the World Obesity Atlas estimates the total cost burden will exceed four trillion dollars by 2035, or roughly three percent of global GDP.

Against this backdrop, new weight-loss drugs have changed the tone of both medicine and markets. Older anti-obesity drugs typically helped patients lose only 3 to 11 percent of body weight and often came with safety issues. The new generation of incretin-mimetic drugs, led by GLP-1 receptor agonists such as Novo Nordisk’s semaglutide (Ozempic and Wegovy) and Eli Lilly’s tirzepatide (Mounjaro and Zepbound), routinely achieve weight loss above 20 percent. These drugs act by stimulating receptors in the gut and brain that regulate insulin release and appetite, while slowing how fast food leaves the stomach. The results have been so striking that the chronic weight management market is now seen as one of the largest potential growth areas in all of biopharma.

What makes GLP-1s even more remarkable is how quickly their use is expanding beyond obesity and type 2 diabetes. In the last year alone, the FDA has approved these drugs for cardiovascular risk reduction and, most recently, obstructive sleep apnea. Trials are now underway for chronic kidney disease, fatty liver disease (MASH), and even neurodegenerative conditions such as Alzheimer’s and Parkinson’s. Early signals suggest they might also reduce the risk of certain cancers and curb addictive behaviors like smoking or opioid use.

Taken together, GLP-1s are not just weight-loss drugs anymore. They are evolving into a metabolic control platform that could touch nearly every chronic disease linked to lifestyle, inflammation, and aging. That is why Pfizer and Novo are spending billions to stay at the front of this wave.

Metsera was founded around a simple but ambitious goal: to re-engineer the GLP-1 molecule so it lasts longer, works at lower doses, and can be manufactured at scale. The company calls its approach nutrient-stimulated hormone or NuSH bioengineering, a way of fine-tuning natural metabolic peptides so they stay active in the body for weeks instead of days. In an obesity market now limited by how fast companies can make and ship peptides, Metsera’s bet is that smarter molecular design will ultimately lead to the headline weight loss numbers that define this space.

Its lead drug, MET-097i, is an injectable GLP-1 therapy built for once-a-month dosing. In early studies, patients lost an average of about 7.5 percent of their body weight after just over a month, and 14 percent after 28 weeks, which is roughly in line with today’s best-in-class drugs like Wegovy and Zepbound. What caught attention was not only the amount of weight loss but also the drug’s apparent durability and tolerability. Weight loss kept going beyond six months with no sign of plateau, and only a handful of patients stopped treatment because of side effects. Still, the long-term effects remain to be seen, and monthly dosing, while convenient, will have to prove it can sustain that efficacy over time.

Beyond the lead shot, Metsera is already working on a family of next-generation weight loss drugs. One combines MET-097i with an amylin analog to further suppress appetite and improve glucose control. Another targets the GIP and glucagon pathways for stronger metabolic effects. Perhaps the most interesting part of Metsera’s pipeline is its oral GLP-1 program, which could change how patients take these drugs entirely. Using what the company calls its “MOMENTUM” delivery platform, Metsera is testing pill versions of its long-acting peptides that aim to achieve the same weight loss seen with injectables at lower doses and lower cost. If successful, this could open a new front in the race to make GLP-1 therapy as easy as taking a daily vitamin.

Pfizer has tried and failed more than once to build its own obesity franchise. Over the past two years, the company has shut down three separate GLP-1 programs after disappointing data and safety concerns, including its once-promising oral candidate danuglipron, which was halted over liver toxicity, and another called lotiglipron, which showed similar issues. By mid-2025, Pfizer’s obesity pipeline was down to a single early-stage GIPR program, leaving it far behind Novo Nordisk and Eli Lilly in one of the fastest-growing markets in medicine.

Given the size of that opportunity, Pfizer could not afford to sit out. When Metsera released mid-stage data showing its lead drug, MET-097i, produced double-digit weight loss with unusually mild side effects and the potential for once-monthly dosing, Pfizer saw an opening. Rather than spend years rebuilding its own internal pipeline, it decided to buy one of the few biotechs showing results that could compete head to head with Wegovy and Zepbound.

The acquisition gives Pfizer something it has been missing: a differentiated GLP-1 asset with strong tolerability, long duration, and room to grow into combinations and oral forms. For a company that had been forced to abandon its own molecules, Metsera offered a second chance with real data, a clear scientific rationale, and a story the market already believes in.

This is what a new playbook looks like. Five years ago big pharma shied away from crowded categories. Today they chase proven biology at scale and let platform math drive the upside. Pfizer moved first with a $7.3 billion structure that included $4.9 billion upfront and $2.4 billion in milestone payments. Novo then fired back with up to $9 billion, including $6.5 billion in equity value and $2.5 billion in contingent payments, and structured a dividend that reduced risk for Metsera’s shareholders. Metsera’s board called Novo’s offer superior and triggered a four-day clock. Pfizer called the move reckless, raised antitrust concerns, and hinted it would fight back in court. In reality, this is not just about who pays more. It is a test of strategy, timing, and risk tolerance.

Scientifically, Metsera looks real enough to bet on, but not proven yet. The lead peptide produced double-digit weight loss at 28 weeks with fewer side effects than expected. The early signal of continued weight loss beyond six months is encouraging, but durability over a year remains untested. Monthly dosing could be the real breakthrough if the efficacy holds and patients stay on therapy.

Strategically, Pfizer needed this more than Novo. After a string of failed GLP-1 programs, Pfizer needed a way back into the obesity race, and Metsera gives it one. For Novo, the motivation feels defensive. The company is under pressure as growth slows, copycat drugs spread, and Lilly pulls ahead. Acquiring Metsera would buy Novo optionality, a hedge against its own slowing pipeline, and a way to keep a potential threat out of competitors’ hands. The problem is regulatory overlap. A Pfizer deal would likely close cleanly, while a Novo acquisition could get stuck for months or even blocked by antitrust regulators. That risk makes Novo’s offer less valuable in practice, no matter what the headline price says.

So, is Metsera for real? My answer is a cautious yes. The biology is validated, the engineering looks smart, and the early data are competitive. But the story only becomes truly real if monthly dosing delivers durable weight loss with consistent tolerability and scalable manufacturing. If those boxes are checked, Pfizer’s move looks prescient. If not, Metsera will still be a strong asset, just not the category-defining one both buyers hope it will be.

Here is what I am into:

What made my cry happy tears
Miguel Rojas hit a home run in the ninth inning to take the Dodgers’ win probability from 8.7% to 44.2% in Game 7 of the World Series. In my opinion, it is the most important swing in the history of the franchise. Oh, and he had been hitless for a month coming into this. Watch here.

What I’m rewatching
Inspired by the Louvre heist, I’m back on one of the best heist stories ever put on television: La Casa de Papel (Money Heist). The pacing, the score, the tension. Just stop after Part 2. The seasons after that are… not that good.

What I’m worried about
After reading the NYT magazine piece on “Buy Now, Pay Later,” I can’t stop thinking about how easy it’s become to finance a lifestyle we can’t actually afford. You can Klarna a burrito, Afterpay a vacation, and never see the full bill until it’s too late. It is credit without the guilt until the payments start stacking up. It feels less like financial innovation and more like a slow drain disguised as convenience.

What made me laugh
And speaking of baseball, here’s a stand-up clip I rewatch every year when both football and baseball are in full swing in October. It’s a perfect compare-and-contrast of the two sports and still makes me laugh every time.

Thanks for joining me on this edition of the newsletter. I’d love to hear your thoughts, comments and feedback. You can reach me at [email protected]

Yours truly,
Gad