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‘Breakthrough’ obesity drugs that have stunned researchers

nature.com

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Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#161

Post by drdeca »

kenjackson wrote: post #133
rajin444 wrote: post #56

This drug is a net good for society, but we have to fix the root problem. Much of the food we eat is filled with addictive ingredients (sugar, excess fats/oils, etc) that provide little nutritional value but are highly addictive. We’re subsidizing companies that create unhealthy addictive food and subsidizing companies to create drugs to counter the unhealthy addictive food. This is an enormous waste of resources.

Isn't all food addictive? Is there something more specific you mean about addition when it comes to these foods? It seems like it may be more about caloric density than addiction.

In what sense is "all food addictive"?

If you just mean "if you don't eat, you die", I don't think that qualifies as an addiction.

If you mean "if you suddenly eat a lot more for some meal than you usually do, you will likely be more hungry the next day than usual", I also don't think that really qualifies. It's not the same kind of thing?

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#162

Post by dougmwne »

iammjm wrote: post #20

At a risk of being ignorant: Isn’t obesity a function of calories intake and calories burn rate? If so, why do we even need a drug for that? What should a possible drug target here? Assuming no changes in behaviour and thus a continued steady daily caloric surplus, would it even work?

Yes, your instinct is correct, you have vastly oversimplified it in an unhelpful way. The body is not an energy equation to be balanced.

The desire to eat is driven by our hormones and these are not easily overridden by willpower. In fact, study after study shows that willpower is insufficient for most people. Hunger is produced by a complex set of factors that we do not fully understand. What we eat and how we live plays a big part in how hungry we feel.

Calories should not be counted like some fungible currency. Each food is a complex and poorly understood cocktail of organic chemistry. Food is not processed by the body in the same way or at the same speed. In the most simple sense, unprocessed whole foods digest the slowest and provide the most even energy to the body, while highly processed food is digested quickly and leaves you hungry again soon. And above all else, fiber is the most amazing thing that can be in your food to regulate your digestion and make you feel more full.

And the consumption of energy is also not a matter of willpower to go to the gym. The body regulates is caloric burn to suit its environment, again, based on a complex and poorly understood web of signals. But in simple terms, trying to eat less can also caus your body to go into a "low power mode" where you burn less energy, ultimately being counterproductive.

The magic of this drug is that is hijacks one of the important hormone pathways involved in hunger and causes you to eat less calories without a single conscious thought. If proven out as safe and effective, it could be the silver bullet in an obesity epidemic that has never had any easy solutions before.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#163

Post by nindalf »

tptacek wrote: post #151
nindalf wrote: post #119

Earlier quoted context omitted.

Because sometimes you’re dealing with the real article. This isn’t a boner pill made of rhino horn. This has been proven in double blind studies, FDA approved and has changed the lives of thousands of people. This could potentially halt the obesity epidemic, preventing many early deaths and improving the quality of life of countless others. At that point, such headlines are justified. What would you have written inst…

Too much of this thread is debating whether these drugs are a good thing or a bad thing, and not enough is on the underlying science story, which is what HN "should" be interested in. What's happening with these drugs --- that you can replicate much of the effect of bariatric surgery with an injection --- is super interesting, and didn't seem to be on the horizon 10 years ago.

Agreed. I don’t think I’ll ever need these pills but I think in ten years we’ll think they’re the second most impactful thing to happen last year.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#164

Post by imranq »

rajin444 wrote: post #56

This drug is a net good for society, but we have to fix the root problem. Much of the food we eat is filled with addictive ingredients (sugar, excess fats/oils, etc) that provide little nutritional value but are highly addictive. We’re subsidizing companies that create unhealthy addictive food and subsidizing companies to create drugs to counter the unhealthy addictive food. This is an enormous waste of resources.

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.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#165

Post by dcolkitt »

iammjm wrote: post #20

At a risk of being ignorant: Isn’t obesity a function of calories intake and calories burn rate? If so, why do we even need a drug for that? What should a possible drug target here? Assuming no changes in behaviour and thus a continued steady daily caloric surplus, would it even work?

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 this weight.

Most people will have a +/- 25 lbs window, where the feedback loop is minimal. But once they step outside this window the nudges become increasingly strong. This is why it's generally easy to lose 15 lbs, but really hard to lose 50 lbs. Also why many can lose weight under very targeted lifestyle interventions, but rapidly snap back as soon as they relax even a little bit. Finally it's why the vast majority of normal weight people don't need to count calories, their metabolic setpoint intuitively matches their appetite to their caloric needs.

"Eat fewer calories" is technically a solution, in the same way that "stop drinking alcohol" is a solution for an alcoholic. The problem is someone who has an obese-level metabolic setpoint will literally be ravenous 24/7 once they get down to healthy weight. If you haven't experienced this yourself, try fasting for 48 hours, putting out a bowl of chips on the table in front of you, and resist the urge to eat even one while you try to do something else. That is what it's like to be an obese person trying to lose a large amount of weight.

GLP-1 agonists work by short circuiting the hormones that regulate hunger. It's basically the equivalent of moving your metabolic setpoint 100 pounds lower. The need to explicitly count calories no longer exists, because your appetite will naturally limit itself well below the point of caloric expenditure.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#166

Post by [deleted] »

dcolkitt wrote: post #152
rajin444 wrote: post #56

This drug is a net good for society, but we have to fix the root problem. Much of the food we eat is filled with addictive ingredients (sugar, excess fats/oils, etc) that provide little nutritional value but are highly addictive. We’re subsidizing companies that create unhealthy addictive food and subsidizing companies to create drugs to counter the unhealthy addictive food. This is an enormous waste of resources.

Disagree. People genuinely enjoy those foods, because they're tasty and flavorful. And there's zero reason to believe that they're substantially unhealthy unless consumed to the point of sustained caloric surplus. We know this because we have hunter-gatherer populations who consume 50% of their diets in sugar (e.g. the Hadza) or fats (e.g. Intuit), and they have none of the diseases of abundance found in modern popul…

[deleted]

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#167

Post by tptacek »

maxlamb wrote: post #158
kenjackson wrote: post #133

Earlier quoted context omitted.

Isn't all food addictive? Is there something more specific you mean about addition when it comes to these foods? It seems like it may be more about caloric density than addiction.

You find broccoli addictive?

Hell yes. Have you ever roasted it with some lemon slices? Or broken up all the individual florets with a mandolin and tossed it as a salad? Whirred it into a soup? Broccoli is incredible.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#168

Post by [deleted] »

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…

[deleted]

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#169

Post by mjmahone17 »

maxlamb wrote: post #158
kenjackson wrote: post #133

Earlier quoted context omitted.

Isn't all food addictive? Is there something more specific you mean about addition when it comes to these foods? It seems like it may be more about caloric density than addiction.

You find broccoli addictive?

Not OP but I do. If I had a plate of steamed or roasted broccoli available on demand at any time, I would eat it like most people do chips. Broccoli tastes great, but requires a lot more prep than “junk food” to get there.

I eat junk food mainly because it takes me no effort and still tastes good: for me the addiction is not having to put in any effort to be satiated, more than the taste itself.

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