[mbostleman]

Actually I recently listened to a fascinating hour long interview with Lotte Bjerre Knudsen (ACQ2 podcast) from which I learned that the original research started in the early 90s. I'm not an authority but I'm pretty well aware of the history. However, I'm still waiting for the other shoe to drop if you don't mind.

And I don't care about votes up or down. But I appreciate your theory on how they're playing out!

[cthalupa]

Is there a law of nature that says a chemical compound has to have a side effects of medical concern for a significant portion of people that ingest it?

One of the most commonly consumed drugs on the planet seems to indicate there is no such thing - caffeine in reasonable quantities is tolerated by the overwhelming majority of human beings and research indicates that even outside of the stimulant effects that humans use it for, it is beneficial. We have significant evidence that caffeine in the 100-400mg per day range decreases risk of heart disease and stroke, and smaller but still compelling evidence that it is protective against diabetes.

Irregular use does seem to cause a small increase in heart rate and blood pressure, but this fades in the overwhelming majority of users as they make the usage more regular.

Too much can cause adverse outcomes, such as anxiety, and in some people timing might be important for maintaining sleep quality, but the vast majority of us would see positive impact from consuming a cup or two of coffee in the morning with little to no concern around side effects.

[mbostleman]

Absolutely, I'm sure there's all kinds of drugs that are totally safe. And I have no reason to think that this one isn't. But it does seem to follow a classic pattern - people get unhealthy because modern life and technology have removed them, in a period of decades, from the environment, incentives, and activities that have shaped their bodies for millennia. And rather than looking at the simpler solutions - in this case just being more active and eating better - some new technological solution is created to fix the problem that the earlier technologies accidentally created. Then the cycle continues and other non-intended consequences ensue. So that's all I'm saying - it's interesting to watch humanity progress. Hope it works out for everyone and it's a smashing success!

[cthalupa]

> And rather than looking at the simpler solutions - in this case just being more active and eating better

I think this is the part where the argument falls apart, though. My relationship with food is vastly different now than it was when I was a teenager or in the front half of my 20s. It was easy for me to eat a healthy amount of food and exercise. I never struggled with it. It didn't take any particular amount of willpower to avoid overeating. I even was able to fairly easily bulk and cut because I was focused fairly heavily on lifting weights - the bulking was harder for me than the cutting!

But as I got busier with other aspects of my life, it became easier and easier to just grab some fast food, or swap over to eating almost entirely uber eats during the pandemic. Before I realized it, it was suddenly very hard to eat less. It was still possible - I would lose weight, manage my eating, exercise, etc. - but something would always happen that caused me to lose track and backslide. A huge project at work, a bad breakup, tearing my meniscus while lifting. But all of these attempts took significant effort and willpower from me, something that I had never struggled with before. It wasn't my metabolism slowing down - I was always hungry in a way that I had never faced when I was a slimmer person, and fighting it caused significant impact to my mood, ability to focus, stress levels, etc. Tirzepatide has put my relationship with food and hunger back to being much closer to how it was when I was younger.

There are tons of feedback loops that are well documented that makes it more and more difficult to lose weight once you've put it on and kept it on for a while. It's certainly true that there's no magical situation where people can eat fewer calories than they use and not lose weight, but for a huge amount of people, these GLP-1 medications are a far simpler solution.

> Hope it works out for everyone and it's a smashing success!

Me too!

[aantix]

> just being more active and eating better

You're grossly underestimating the problem.

40+% of the population are obese.

This isn't just a few pounds to lose. This is 60, 70, 100lbs.

The task is to lose the weight forever.

For which long term weight loss success numbers are abysmal.