‘Breakthrough’ obesity drugs that have stunned researchers • Hacker News Board

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#361

Post by empathy_m » Wed, Jan 04, 2023, 9:46 PM UTC

Aaronstotle wrote: post #265

0xB31B1B wrote: post #21

I’m currently taking one of these drugs and it has been no less than a miracle in my life. I became obese when I was around 5, topping out around a 34 BMI. When I was 20 I lost a substantial amount of weight the old fashioned way (diet and exercise), and within 8 months I was BMI 23. Losing weight was extremely challenging and socially isolating. 7 years later, I had a bad ankle injury and regained weight to about 29…

[flagged]

I was personally capable of tracking 100% of my caloric input and output to manage to a target weight. I lost 25% of body weight and kept it off for a long time (years).

However, now that I have a full-time job and am also primary caretaker for two young children under age 5 with minimal childcare, I have been unable to maintain the weight loss and I'm fairly close to lifetime maximum weight (at -5% right now).

I notice behaviors like eating snacks between meals (often high-calorie), eating the kids' leftover food when I clean it up, not tracking my calorie inputs, eating at meals until I'm full (which tends to lead to lifetime maximum weight quickly in my experience), and eating extra food at night after the kids go to bed. This all adds up fast.

A couple of years ago I read the literature about GLP-1 agonists and started thinking about drugs. The last time I asked, a couple years ago, my GP said she had never successfully gotten an Rx approved for GLP-1 agonists in a patient with obesity. I was also thinking about looking into cognitive behavioral therapy as this all feels like it's behavioral?

In general I prefer low-intervention approaches to medicine. I'd definitely rather rely on diet + exercise alone for weight loss. However, I just don't have the time in the day to lose enough weight - mechanically it just isn't working. It's frustrating because it used to. I'm pretty close to looking into the drugs again.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#362

Post by imranq » Wed, Jan 04, 2023, 9:46 PM UTC

mym1990 wrote: post #230

imranq wrote: post #164

Earlier quoted context omitted.

I agree that we have incredible waste on both sides, but there is an even greater culprit: people are lacking true meaning and purpose in their lives and are indulging in these foods to distract themselves from their inner emptiness.

This is a pretty big leap, what is even "true meaning and purpose"? The culprit is that this food is literally everywhere and billions of dollars are poured into research everywhere to design systems that entice humans to take the convenient way out. If I was to go along with your hypothesis, I would alter it to say that poor nutrition is what contributes to a person's lack of "true meaning and purpose".

I agree that society has been designed to make things more and more convenient in the name of progress and that we haven't made the nutritious food convenient yet. Stated another way, poor nutrition is the default choice in most of the western world.

Still, I think its possible to make the idea of "purpose" more concrete. You could define "true meaning and purpose" to be goals that are greater than oneself that require one's full potential in mind and body and sacrifice of immediate pleasures for long-term gain. The widespread nature of obesity indicates that many people don't consider a healthy body as necessary for their goals and hence don't sacrifice immediate food gratification for those goals. Hence most people don't have goals that require their full body potential.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#363

Post by valarauko » Wed, Jan 04, 2023, 9:46 PM UTC

asdff wrote: post #199

dcolkitt wrote: post #165

Earlier quoted context omitted.

Modern nutrition science has found that each person, at any given time, has a "metabolic setpoint". This is basically a target weight that their endocrine system is trying to keep them at. There's a feedback loop, where below this weight hunger hormones will nudge them to eat more and metabolic hormones will lower caloric expenditure (lowering body temperature, sleeping longer, fidgeting more). And vice versa above t…

People have trouble dealing with hunger because we frame it all wrong in the western convention. I'm hungry, I should eat a little something, is what most people think. An ascetic from the east who fasts is not immune to the pain of hunger, they just understand that hunger is a sensation that is neither good nor bad, and what they choose to do with that sensation is up to them, and they are not bound to it and do not…

As someone from an Eastern country with a strong ascetic tradition, I find this framing unhelpful. Yes, our culture places a strong emphasis on fasting, but is simultaneously also experiencing its own obesity epidemic - and it's not because we're adopting a western framework around hunger. More and more people can now afford high calorie ingredients in our native cuisines that were a luxury a few decades ago. When I was a kid, things like ghee were prohibitively expensive, and I grew up seeing it as a special treat consumed sparingly. I never had to develop self-control around expensive, high satiety food because access was self limiting. If all we could afford to eat daily was rice and lentils, it was hard to be morbidly obese. My generation has faced an obesity epidemic, partly due to easy access to rich foods my ancestors didn't have but my culture and cuisine valorizes. Industrialization of food production has made access much more egalitarian, but we have yet to develop the collective restraint needed.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#364

Post by paulpauper » Wed, Jan 04, 2023, 9:46 PM UTC

1024core wrote: post #336

smooth_remmy wrote: post #275

Petro Dobromylskyj is one of the foremost experts of fat metabolism. He has a blog called Hyperlipid where he's been blogging about fat metabolism and interpreting research for close to 10 years. He thinks the GLP-1 inhibitor drugs will be a disaster in the long term because they 1) cause weight loss but also 2) cause the body to create lots of new adipocyte (fat cells). Increasing the number of adipocytes is very un…

Given that injections cost ~ $1000/month, you're saying basically that it'll be a great recurring revenue stream for the companies. A CFO's wet dream.

consider that treating obesity-related consequences also costs money and enriches companies as well. I think its worth it

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#365

Post by darkwater » Wed, Jan 04, 2023, 9:46 PM UTC

dcolkitt wrote: post #304

Gatsky wrote: post #178

Earlier quoted context omitted.

There are randomised controlled trials of diets (without caloric restriction). They show that some diets are better than others for real clinical endpoints, eg mediterranean vs low fat diet for secondary prevention of cardiac events [1]. The effect size in that example is not small, it is large, despite most participants already being on a statin. This data shows that diets are biologically active and significantly i…

You haven't controlled for body weight changes though. Nobody doubts that diets (if adhered to) can reduce weight. So if biomarkers improve relative to an alternative diet, the question is it because A) the Med diet is more effective at weight loss, or B) the Med diet has benefits outside weight loss. The research you linked is interesting, but confounded by weight loss. Research that has directly tried to control fo…

You just forget that there might be side-effects showing up in the long-run that we simply don't know yet (and possibly), why the mediterrean diet has been tested for a few hundred years already (where "diet" means what we have access to and eat, and not a small subset of foods forced on us that relies on a lot of mental effort to follow)

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#366

Post by rootusrootus » Wed, Jan 04, 2023, 9:46 PM UTC

tayo42 wrote: post #339

Volundr wrote: post #284

Earlier quoted context omitted.

Maintaining a healthy weight is not that difficult FOR YOU. Many, many people struggle to control their weight. One day you might too. I never had an issue with my weight until I had a thyroid infection around 30. I now have "normal" thyroid levels, but ever since then maintaining my weight take vigilance and lots of discipline. It's possible, but definitely "difficult".

Why? How many calories do you eat in a day?

Have you ever tried to deliberately eat fewer calories every day than your body wants, for an extended period of time? Like, months and years, not days.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#367

Post by Volundr » Wed, Jan 04, 2023, 9:46 PM UTC

tayo42 wrote: post #339

Volundr wrote: post #284

Earlier quoted context omitted.

Maintaining a healthy weight is not that difficult FOR YOU. Many, many people struggle to control their weight. One day you might too. I never had an issue with my weight until I had a thyroid infection around 30. I now have "normal" thyroid levels, but ever since then maintaining my weight take vigilance and lots of discipline. It's possible, but definitely "difficult".

Why? How many calories do you eat in a day?

None of your business. I maintain a healthy weight. Even that is none of your business.

How many calories I eat does not change it being difficult to maintain.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#368

Post by claytongulick » Wed, Jan 04, 2023, 9:46 PM UTC

Aaronstotle wrote: post #265

0xB31B1B wrote: post #21

I’m currently taking one of these drugs and it has been no less than a miracle in my life. I became obese when I was around 5, topping out around a 34 BMI. When I was 20 I lost a substantial amount of weight the old fashioned way (diet and exercise), and within 8 months I was BMI 23. Losing weight was extremely challenging and socially isolating. 7 years later, I had a bad ankle injury and regained weight to about 29…

[flagged]

This discounts cognitive process and the factors that influence it.

You can make the same argument for infidelity - just don't cheat on your spouse. Yet, infidelity is an incredibly complex issue that stems from multiple biological and social variables.

I'm not a big fan of taking drugs to treat weight. You could also treat infidelity with hormone treatments that remove all of your sex drive - but that's like putting out a fire with a bomb.

Much like with infidelity, I believe it's better to address the underlying reasons for weight gain and treat those, but we shouldn't be under any misconception that it's an easy problem.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#369

Post by MajimasEyepatch » Wed, Jan 04, 2023, 9:47 PM UTC

bioemerl wrote: post #182

> In the past, scientists and the public often thought that those with obesity simply lacked the willpower to lose weight. But evidence is growing that most people’s bodies have a natural size that can be hard to change. In the context where we have gone from obesity rates of 13 percent to 40, to suggest that people have a natural weight and that's the cause of this seems absurd to me.

The term "natural weight" as used here is misleading. It does not mean that people are supposed to be a particular weight. It refers to the idea that something—whether it's diet, genetics, environmental factors, or something else—influences the body's weight regulation mechanisms to "prefer" a certain body weight, and changing that is very, very hard.

Think of it like body temperature: normally, your body maintains a certain core temperature, and it will respond in a negative feedback loop when the temperature deviates from that set point. Conditions like infections can induce where your body raises that set point to fight the infection, and it takes time for that set point to come back down.

Something similar appears to happen with people's weight. Hormonal or other changes cause the body to gain weight, and once that happens, it resists losing weight in various ways: increasing appetite, changes to basal metabolic rate, changes to metabolic pathways involved in breaking down nutrients from food, all sorts of things. Deviously, fat cells actually produce hormones that play into these changes, which is one of many reasons why losing weight is usually harder than gaining it. And when people do manage to lose weight, often after a huge exertion of effort and willpower and major lifestyle changes, their set point may not have changed, and so as soon as they slip up even a little bit, they quickly regain back to their set point.

So they're not suggesting that there's some mystical force out there that decides some percentage of the population should be overweight. They're referring to the idea of a set point for body weight that is difficult to change without drugs or bariatric surgery.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#370

Post by paulpauper » Wed, Jan 04, 2023, 9:47 PM UTC

JamesBarney wrote: post #282

smooth_remmy wrote: post #275

Petro Dobromylskyj is one of the foremost experts of fat metabolism. He has a blog called Hyperlipid where he's been blogging about fat metabolism and interpreting research for close to 10 years. He thinks the GLP-1 inhibitor drugs will be a disaster in the long term because they 1) cause weight loss but also 2) cause the body to create lots of new adipocyte (fat cells). Increasing the number of adipocytes is very un…

With every weight loss intervention when you stop you gain back the weight. GLP-1 agonists don't seem to be any different than another other intervention.

gastric bypass does not have this problem as bad