A new class of drugs for weight loss could end obesity | Hacker News Reader

A new class of drugs for weight loss could end obesity

economist.com

22 pointsbumbledraven48 comments

The real money quote is: "A bigger drawback, however, is that those who start taking the new drugs are likely to depend on them for life. Stop, and the weight piles back on, just as with most conventional diets."

This is a drawback, but I'm not sure how terrible it is.

If you go off the drug, you regain your weight. If you go off your diet, you also regain the weight. That, then, is a wash.

These drugs currently cost a fortune, so lifelong dependence is an expensive scenario, especially since most insurances refuse to cover them. On the other hand, this is preventative medicine, which might significantly reduce costs from obesity-related health issues down the road, including heart disease, cancer, and arthritis.

Compliance with a weekly injection is also likely to be higher than compliance with a long-term dietary change. Of course, since something like 95-plus percent of diets fail long-term, almost anything would have a higher compliance.

I don't know that we have enough data on long-term use of these drugs to be confident about long-term side effects, either.

I don't love the idea of being dependent on a medicine for the rest of my life, but there are plenty of other lifelong medicines that we just sort of accept as normal now. Insulin-dependent diabetics and people with high blood pressure are just two examples.

I guess for now I'm putting these in my "cautiously optimistic" bucket.

100% agreed. I currently wouldn't take it just because it seems to have pretty drastic effects, and we don't seem to quite understand on what or how.

The reported side-effects like 5% have nausea or whatever, don't seem too bad. Prices will inevitably come down if these go mainstream.

Would I snap my finger like Thanos and obliterate obesity in natural ways if I had the 7 rings or whatever?

Yea, but I don't. This is a decent alternative, it seems. If there are no serious long-term side-effects.

"Like dieting but easy, just pop a pill" still seems like a huge net positive for society.

"like dieting" may be an improvement over nothing, but it's a far cry from "better diet".

This is a technological fix to a personal (or societal problem) which doesn't address the underlying problem. At least "dieting" requires you to face the problems in what you eat and how much exercise you do, this takes even that away.

Not even pop a pill - take an injection weekly, at home. Zero stigma, nobody will even know you're on it.

If these drugs prove workable over the long term, pretty soon everyone will suspect you're on it, because the majority of people will be. There would be no more of a stigma about this than taking a medication for blood pressure.

100%.

I've heard the theory that once we discover the cure for obesity, it'll be over in 2 years and nobody will miss it. What, like 40% of Americans are currently dieting at any given time? And that's with a ~0% success rate.

There's nothing to discover cause it's not a secret: be more active, eat better & less food.

Don't have a clear picture of what "better" mean? That's also simple. Look at what people were eating 100 years ago, and how much physical activity they were doing then.

Or, look at other countries across the world today.

WW1 military rations, from https://net.lib.byu.edu/estu/wwi/memoir/ration.html

  > British Daily Ration, 1914:
  > 
  > 1 1/4 lb fresh or frozen meat, or 1 lb preserved or salt meat;
  > 1 1/4 lb bread, or 1 lb biscuit or flour;
  > 4 oz. bacon;
  > 3 oz. cheese;
  > 5/8 oz. tea;
  > 4 oz. jam;
  > 3 oz. sugar;
  > 1/2 oz salt;
  > 1/36 oz. pepper;
  > 1/20 oz. mustard;
  > 8 oz. fresh or 2 oz. dried vegetables;
  > 1/10 gill lime juice if fresh vegetables not issued;
  > 1/2 gill rum;
  > not exceeding 2 oz. tobacco per week.

So, mostly meat, bread, bacon, and sugar?

This is not a productive comment. Comparing military rations to what civilians eat is apples and oranges. The focus of military rations is getting enough calories and to avoid any short-medium term health issues (notice the conspicuous reference to a lime juice ration to fight scurvy).

But let's take it at face value, these rations are calculated for target activity level. Any idea of what that is? Cause I'm pretty confident that it's higher than the sedentary North American lifestyle.

Studies from the 20s thru 40s for somewhat sedentary office workers in NYC show that they ate more the less physically active they were, often eating up to 4,500kcal/day. Large portions of that from white bread, lard, butter, milk, and pork.

> Don't have a clear picture of what "better" mean? That's also simple. Look at what people were eating 100 years ago, and how much physical activity they were doing then.

Do you mean fructose? PUFAs? Be specific. What do I eat/avoid?

Pick a region of the world either now or in the past, that is not obese and is not starving.

Look at what they eat and how active they are in their daily lives, and then do that.

I’m not saying that there is only 1 answer for what this looks like, I’m happy to say that there are countless viable options that deal with the obesity and this is demonstrably true since these were not problems in the past.

So I should spend 8h per day farming rice?

Doesn't seem like a productive comment.

There are certainly countless viable options, but I've yet to see someone suggest one that doesn't require me moving to another continent to become a physical laborer.

Until it inevitably turns out you get cancer from it

I'd be lying if I said I wasn't excited by the discovery of semaglutide. I'm not particularly heavy (BMI of 26.5) but I would happily pay for it if it was available over the counter.

I wonder how long that will take, if ever.

Don't know about OTC but patents last 20 years. So the generics will be out then. And you could get it prescribed by your doctor w/o a big deal like blood pressure meds or something now. I got a CGM prescribed just cause I wanted one. No biggie.

https://archive.fo/4eE2y

I always wondered what happens when your ulcer flares up. If I would develop a drug that takes away appetite then get someone with ulcers and check what signal is sent to where and try to imitate that. Ulcers are the best when you need some weight loss.

Honestly not sure how I feel about people being able to be absolute gluttons then just take a pill and have no consequences. I can't imagine a move to healthier eating or lifestyle afterwards.

You misunderstand the mechanism of action.

You cannot be a glutton on this class of drugs. They make you not want to eat, and that’s how weight loss is achieved.

Think back to a time when you had a gastroenteritis. There is a period after vomiting where you are fine pain wise, but have a mental opposition to eating. That’s the sensory feedback these drugs give to your HPA axis.

Haha hopefully without the disgust ;) edit: oh wait, is this why they sometimes cause vomiting? Like you literally feel sick?

>is this why they sometimes cause vomiting

I would speculate yes, but Im not an expert.

GLP-1 seems to be the primary signal of “nutrient in the gut”.

What happens when you mechanically overwhelm your gut? You throw up. What happen when you have gastroenteritis? You want to get everything out of your gut.

Similarly, gastric bypass surgery directly affects GLP-1 secretion (increasing it), which has the effect of causing people to not want to eat/ feel nausea with much lower nutrient intake.

Sounds horrible. Why don’t people just learn how to fast?

Prebiotic fiber while fasting feeds gut bacteria so you won’t feel overwhelming hunger. Electrolytes/mineral-salt stop “fasting headaches.” With prebiotics and drinking tea my stomach doesn’t even growl while fasting, and I’m more productive. Most people just need to try and they’ll find it’s easier than they thought.

I've fasted a ton including every sort of IF and up to 7 days water/10 days fat fast. Didn't do anything for fat loss. Read here if you care: https://exfatloss.substack.com/p/19-fat-loss-experiments-ive...

Your food pyramid is hilarious: https://exfatloss.substack.com/p/ex150-diet-macros-2294kcal-...

If it works for you OK - but I'm not a fan of dairy or red meat. I'm very close to my ideal weight anyway with my current diet and intermittent fasting. (I do two 36 hour fasts per week if trying to lose weight)

Ha, thanks :)

Behavioral modification has been shown to fail upwards of 97% of the time. Argue all you want, and I will show you trial failure after trial failure of every known behavioral approach.

Sounds like a doctor told his obese patients they need to restrict their calories. Then 97% of them didn't listen. Big surprise - how is knowing that useful to anyone?

If instead you choose to be your own doctor, research the best approach you think might work and take responsibility for your health, then you have a good chance of succeeding. People can't be told what to do, they have to discover it.

Nope. Even in intensive interventions, eventually the weight comes back on. Even for people with high executive function.

Yes, unfortunately it requires a lifestyle change. Keeping it off is harder than losing it to begin with, because you enthusiasm for the diet wears off. By then you have to have formed eating habits that don't lead to weight gain. Even so, for some people it will require discipline.

Serious q, what would you recommend instead?

I am not a medical professional so I cannot make medical recommendations.

In terms of policy, gastric bypass appears to be the sanest policy. Relatively safe, effective, some types are reversible and cheaper than a lifetime of GLP1 agonists.

We need more research into what is driving the obesity epidemic at the brain level. Or if there even is an obesity epidemic vs. humans didn’t evolve with Costco like food availability.

Also not a medical professional but I recommend you eat lots of heavy cream :D https://exfatloss.substack.com/p/ex150-diet-macros-2294kcal-...

I would not recommend that, as it will raise your LDL-C and likely LDL-P.

If someone eats 100% keto, that might not be a problem. But the average Joe is going to think "hey I've heard about this keto thing, that means I should eat more steak and butter". Ultimately this translates to a mixed high saturated fat + carbohydrate diet which is the worst of all worlds.

High sat fat + starch might actually be fine if you cut out the PUFAs and maybe sugar: https://fireinabottle.net/introducing-the-croissant-diet/

Have not tried it yet, but it's on the list (https://exfatloss.substack.com/p/hypotheses)

But yea the diet as listed is keto AF. I test 1.7-2.7mmol/L most of the time when on it.

That's not how the pills work. They act by reducing hunger and creating satiety at lower caloric inputs. They also often have nausea and vomiting as side-effects.

Will be interesting to see how that dynamic acts out. I'm also kind of dumbfounded. E.g. will we just make food even unhealthier and just counter it with more of these drugs? Where eventually we're just chugging soybean oil laced with high fructose corn syrup? :D

I mean could the drug counteract that or is there a limit?

Guess we'll find out.

It seems like we never learn.

There are definitely a group of people who truly need this drug (diabetics), but the obesity epidemic is the result of poor diet and a lack of exercise.

So rather than solving for the problem at the source, we're suggesting a "quick fix" which has some known side-effects, and potentially many more unknown. Historically we look at the drugs that have promised weight loss in the past, and they have all been pulled from the market, or shown to have negative consequences.

Taking the drug likely still doesn't solve the other side of the obesity epidemic, which is exercise. So are we going to pop a pill that exercises for us as well?

What will life look like for future generations when they can eat like gluttons, laze around with robot servants bringing us our every wish, and AI that can think for us?

That's not a future I want to live in. I already see parts of it with the UberEats/DoorDash, etc - where people think they are just too busy to go and do something themselves, then I find out they are watching 3 hours of television and tiktok per day.

I'm tempted to downvote myself for this rant, but I do find this a very worrying state.

Obesity is one of those areas where if you don't suffer from it, solving it seems easy... "just" eat better. "just" exercise.

Problem is, once the body's mechanisms get out of whack, it just doesn't work that way. When you try to lose weight via calorie restriction, especially if insulin resistance has set in, hunger is going to catch up to you. Study after study has shown this.

Drugs like ozempic, metformin, even wellbutrin... They act on those mechanisms, and that's why they result in weight loss. If you think people are taking those medications and then binging, that's honestly not what's going on. Once those feedback mechanisms are under control, you're simply not controlled by hunger anymore. That naturally leads to weight loss.

100% agreed.

Diet advice from naturally thin people is like dunking advice from Shaq. "Just walk up and put it in" won't cut it for those of us who have a screwed up metabolism.

I should have been clearer in my comment. I wasn't saying exercise and diet can cure obesity. We need people to eat healthy and exercise prior to obesity taking hold.

Prevention (and generally being healthy) must be the default to our health problems, not constantly looking for the cure for problems that we caused ourselves. The 2nd option ends up being whack-a-mole.

Obesity is unsolved. If you know what dietary intervention will cause significant long-term fat reduction in a majority of people, please demonstrate and you'll win the Nobel peace price.

We just don't know. Trust me, this is kind of my thing.

That said I am also naturally skeptical of quick fixes. The known side effects of these drugs seem meh, but I worry about hidden ones. E.g. I've heard these described as "chemical starvation" - doesn't exactly sound healthy long term to starve your body?

I strongly disagree exercise has anything to do with the obesity epidemic. Exercise is great but not related to obesity.

edit:

let's debate this guy and not just downvote, plz?

I'm also super skeptical of quick fixes. We've actually had a set of diet pills in the 80s and 90s that were touted as similar miracle workers just like these ones, until they started killing people...

I'm all for trying to help obese people lose weight but what's the difference between these ones and the previous fen-phen craze?

I'm not saying exercise and diet is the cure for obesity.

Good diet and exercise are the preventative of obesity. I didn't state that clearly in my initial comment.

Please, debate (me) "this guy"!

Thanks for clarifying!

> What will life look like for future generations when they can eat like gluttons, laze around with robot servants bringing us our every wish, and AI that can think for us?

Sign me up :D

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