insane money to be made -- Novo had an income that exceeded DK's GDP, for example.

most big pharma orgs flirted with it if not chasing it, so once it looks like there are working solutions they can retool, make knockoffs, steal secrets, bribe (aka hire with competitive rates) R&D staff from other orgs, etc.

I'm sure the morbidly obese are unaware of this.

For what it's worth, I'm an ex-smoker and quitting smoking was easy compared to trying to deny myself unhealthy amounts of food. The vast majority of obese people hate it and don't want to be that way - but they're addicted to food. GLP-1's pretty much stop their cravings. Using them to get to a healthy weight and then trying to manage cravings when they are healthier and happier seems like a good solution. Especially given the side-effects of extreme obesity are severe and well known - better to worry about that than 'unintended side effects' that are at this point hypothetical.

For a lot of people it isn't that easy. There is a reason weight loss surgery has been a thing for a long time. I could easily see using this as a jumping off point along with making choices about what you eat and increased exercise.

There is a psychological aspect to this, you start making those changes along with something like this so you start seeing the changes you are hoping for and feeling better so you keep with it.

The body has sophisticated signaling pathways that regulate hunger and defend fat stores. In some people, dysregulation in pathways like mTORC1 essentially keeps their "hunger volume" turned up regardless of their actual energy needs, increasing hunger-promoting neuropeptides (NPY, AgRP) while decreasing satiety signals (POMC, CART).

When someone with this dysregulation tries to lose weight, the body deploys additional defenses: reduced non-exercise activity thermogenesis (less fidgeting, less spontaneous movement), increased energy efficiency, and even induced lethargy after intentional exercise to preserve fat stores. This isn't laziness - it's sophisticated biological adaptation.

This creates a crucial matrix that determines weight outcomes:

* High willpower + Low hunger signaling: Naturally fit with minimal effort

* Low willpower + Low hunger signaling: Generally maintains healthy weight without struggle

* High willpower + High hunger signaling: Might maintain weight with constant effort

* Low willpower + High hunger signaling: Almost inevitably leads to obesity

Keep in mind willpower itself has significant genetic and epigenetic components - it's not simply a matter of character. Variations in dopamine and serotonin regulation genes directly affect impulse control and reward processing.

GLP-1/GIP medications work by intervening in these pathways. They activate receptors in the hypothalamus that can override or bypass the defective mTORC1 signaling. They directly inhibit AgRP/NPY neurons while activating POMC neurons, essentially normalizing the hunger signals. They also slow gastric emptying and modulate the brain's reward system to reduce food's hedonic value. In other words, they take willpower out of the equation. If you aren't hungry, you don't have to fight the urge to eat.

I'm not just speaking to the science here - I have direct experience. Despite years of disciplined efforts with trainers, various diets, calorie counting I went from 150lbs in my 20s to 315lbs by my 40s. With Zepbound, I've lost 55 pounds in six months without the constant battle. I will have to take this medication for the rest of my life, but I will probably live much longer as a result, and I'm already reaping the rewards in terms of energy, focus, sleep quality, et cetera.

These medications do have side effects worth considering, but they need to be weighed against the severe health consequences of obesity. Obesity significantly increases risk of heart disease, stroke, type 2 diabetes, sleep apnea, certain cancers, and premature death. For men specifically, obesity increases sex hormone-binding globulin which reduces free testosterone levels, leading to fatigue, reduced muscle mass, decreased libido, and even depression. The most common side effects of GLP-1 medications (nausea, constipation, diarrhea) are typically mild, manageable, and often diminish over time. While there are theoretical concerns about more serious effects like pancreatitis based on animal studies, clinical data in humans hasn't supported these concerns. Regardless, these potential risks must be balanced against the near-certainty of health complications from remaining morbidly obese.

For people with dysregulated hunger signaling, these medications aren't just cosmetic interventions—they're addressing a fundamental biological dysfunction that otherwise creates persistent obstacles to maintaining a healthy weight. The risk-benefit analysis strongly favors treatment for those who need it. They make sustainable lifestyle changes possible by removing the constant neurobiological opposition to weight loss.

Let me guess…you have never had a weight problem. As someone who has lost over 170lbs via diet and exercise and battles like hell every fucking day even eight years later to try and keep it all off, it’s laughable to see some people think it’s so simple.