This drug class could be the next GLP-1. Apitegromab, a myostatin inhibitor, just got FDA approval! Myostatin is a protein that tells your muscles to stop growing. This drug inhibits myostatin. It's why Belgian Blue cattle look like Arnold Schwarzennegger. Apitegromab targets the same system by blocking myostatin activation. In patients with spinal muscular atrophy, adding it to their existing treatment improved their ability to move. But its potential could go beyond this. In a study with 102 adults on tirzepatide, half of them also received apitegromab while the other half was given a placebo. After 24 weeks, both groups lost a similar amount of weight, but those on apitegromab lost about half as much lean tissue: 1.6kg vs. 3.5 kg (this combination is still experimental). But this myostatin inhibitor is still compelling. If we safely pair GLP-1s with a drug that can preserve muscle, and it works - it could create demand for an entirely new category of treatment.

This is going to be a fantastic event. @maxmarchione, founder of @superpower, is one of the coolest founders I've ever met. He and team are revolutionizing personal health, and I've loved being one of their clients. Join us in SF on Oct 5. RSVP in @dunkhippo33's link below.

We have a gene that stops us building muscle. Racing dogs without the gene are champion sprinters. Cattle without it are jacked. The MSTN gene produces myostatin, which tells muscles to not grow. So, why would evolution not want us to build muscle? Because more muscle is liability. I believe myostatin is a famine adaptation. Muscle burns energy just sitting there and a gene that prevents you from building more will get you through the winter. The thing is, we don't live in famine anymore. The world we live in today is the world of abundance. Food is unlimited and movement is optional. Mechanisms that evolved to constrain muscle may be maladaptive today and contributing to the obesity epidemic. Which is why the people born with myostatin deficiency have less fat, more muscle, stronger grip, their hearts are fine as well as fertility. I think myostatin inhibitor will be huge because in today's world the brake on muscle isn't needed anymore.

Body positivity movement seems dead. The GLP-1 era exposed exposed how shallow the entire ideology was. The moment effective weight-loss drug arrived, being fit became cultural again. According to Vogue Business analysis of 182 shows, 97.6% of models were straight size. Only 0.3% were plus size. The entire movement collapsed when people were given a way to lose weight and be thin again. Health is becoming cultural in a way it hasn’t been before. Health is in vogue. Looksmaxxing is in vogue. Health is social. Combine that cultural fervor with rapidly improving diagnostics and therapeutics and you get the moment we’re in today.

Alcohol is losing America. Only 54% of adults drink now, down from 62% in 2023, tied for Gallup's lowest reading ever. GLP-1s are showing promise in reducing alcohol cravings so I suspect the industry's worst decade is ahead.

This drug class could be the next GLP-1. Apitegromab, a myostatin inhibitor, just got FDA approval! Myostatin is a protein that tells your muscles to stop growing. This drug inhibits myostatin. It's why Belgian Blue cattle look like Arnold Schwarzennegger. Apitegromab targets the same system by blocking myostatin activation. In patients with spinal muscular atrophy, adding it to their existing treatment improved their ability to move. But its potential could go beyond this. In a study with 102 adults on tirzepatide, half of them also received apitegromab while the other half was given a placebo. After 24 weeks, both groups lost a similar amount of weight, but those on apitegromab lost about half as much lean tissue: 1.6kg vs. 3.5 kg (this combination is still experimental). But this myostatin inhibitor is still compelling. If we safely pair GLP-1s with a drug that can preserve muscle, and it works - it could create demand for an entirely new category of treatment.

This is a dog with a myostatin deficiency, which roughly doubles its muscle mass. Myostatin is a protein every mammal makes to stop muscle growing past a certain point. There are now drugs in human trials that block myostatin on purpose to stop people from losing muscle with age or on GLP-1s. I think myostatin inhibitors may end up as one of the biggest drug classes of the next decade.

The difficult lesson from growing up in Australia is that you either figure out jetlag or you spend a week of every trip half-asleep. I figured it out and now get zero jetlag. There are thousands of things I learnt, but here's the 80/20 when I land: 1.⁠ ⁠Get lots of sun in the morning 2.⁠ ⁠⁠Turn off lights and wear blue blockers at night 3.⁠ ⁠⁠2mg pinealon 4.⁠ ⁠⁠6mg epitalon 5.⁠ ⁠⁠Make sure you are very tired the first night

On Using AI – from our eng lead just then: Using AI is the default. Not using it is a performance issue. Using it as a scapegoat is a professionalism issue. AI is an extension of you. Its output is your output. When something breaks, it is not Claude’s fault. It is yours. If you can’t read the code, neither can we.

"I'm yet to get my blood draw ... but just with old labs & wearables the insights are nothing short of incredible. Truly like nothing I have ever experienced" - Superpower member today

AI doctors are the self-driving problem. Even if self-driving cars are provably safer, adoption takes time. Waymo has now driven more than 220 million fully autonomous miles. Across those miles, it reports: - 94% fewer crashes causing serious or fatal injuries - 82% fewer injury crashes than human drivers in the same operating areas But Waymo didn't need 220M miles before adoption. At roughly 7M fully autonomous miles, it already had statistically significant evidence showing substantially fewer injury crashes than humans. Then adoption accelerated: - 10k rides per week in 2023 - 100k per week in 2024 - 500k per week by 2026 It took about 2-3 years for usage to scale by orders of magnitude. We’ll have the same thing with health AI. We just need enough real-world data to show that people have better outcomes when AI is involved. By the end of the year, we’ll have a health AI that’s provably safer. It’ll take 2 to 3 years for that to diffuse. But I suspect in the next 3 years, AI is going to be prescribing and performing most of the roles of the doctor.

I overstated how interesting this kisspeptin study is. Four problems: 1) Only 32 men completed the trial (all diagnosed with HSDD, not ED) 2) The active treatment was a single 75-minute IV infusion which doesn't really tell us whether effects continue with repeated/long-term use 3) The primary endpoint was changes in brain activity, not better sex or erections or quality of life 4) The 56% was the difference in penile tumescence, not improvement in erectile function The study is a neat mechanistic proof-of-concept, but as evidence for kisspeptin being a serious ED drug, it's a bit of a dud.

"Superpower's AI is light years ahead". Great quote from a member yesterday: "I've used a lot of different AI tools. Superpower's one of them. I've used Perplexity, Claude, Chat, all of them, and none of them gave me this level of analysis. So to me, Superpower, it's like just light years ahead. And I've input similar data and none of them pinpointed this."