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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

#81
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?

At a really fundamental level, yes, it boils down to calories in versus calories out. However, in practice it's more complicated than that, partially for psychological reasons.

Anyone will lose significant weight on a strict enough diet. Unfortunately, severe calorie restriction does things to your metabolism -- basically, your body notices there's not enough food, and tries to slow everything down so that your existing stores will last as long as possible. This (a) isn't good for you, since major organs are having to limp along, and (b) means your diet gets less effective, as "calories out" aggressively shrinks. There's evidence that this lasts for a fair while after a diet stops, making it really easy to regain weight.

Then, psychologically, most people have a hard time sticking with any sort of long term diet. Unless you have an abnormally low hunger response, ignoring feeling hungry all the time (even just a little bit) is very hard. Cheating on your diet is very alluring, and your body gives you all the rewards for doing things that feel like they're avoiding you slowly starving to death.

The latter point is where these drugs come in. By suppressing hunger signals, dieting suddenly becomes easy, removing the escalating willpower requirement. (Honestly, I'd worry about whether you'd still suffer the metabolic effects of calorie restriction even if you're not noticing the hunger, but hopefully that's being studied and they're only prescribed along with a solid nutritional plan...)

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#82
post #70

Earlier quoted context omitted.

What are the certain thresholds? Can we be more specific than lowered all-cause mortality, such as specific diseases we know have causal relationships with obesity specifically? I'm asking because I'm not that educated, but if you know there are studies showing e.g. purely losing weight with no lifestyle changes means less heart attacks, less joint replacements, less cancer, etc. please share.

Caveat: it's generally not possible to "lose weight with no lifestyle changes." Even taking anti-obesity drugs results in lifestyle changes along with the weight loss. https://pubmed.ncbi.nlm.nih.gov/12457296/ https://academic.oup.com/ajcn/article/74/5/579/4737391 https://www.cell.com/cell-metabolism/fulltext/S1550-4131(16)... https://www.bmj.com/content/359/bmj.j4849 https://journals.plos.org/plosmedicine/article?id…

This is exactly what I was looking for, huge thanks.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#83

Earlier quoted context omitted.

Because this isn't an article about biology, it's about health, and health isn't unidimensional

Helping obese people lose weight is unidimensionally a good thing

The article specifically points out that the link between weight and health on its own is in question:

> Some researchers also worry that by offering a weight solution in societies that prize thinness, these drugs could also inadvertently reinforce the disputed link between excess weight and health. One study found that nearly 30% of people who are considered obese are metabolically healthy.

The abstract from that article also points out that a significant share of non-obese people are metabolically unhealthy:

> Nearly half of overweight individuals, 29% of obese individuals and even 16% of obesity type 2/3 individuals were metabolically healthy. Moreover, over 30% of normal weight individuals were cardiometabolically unhealthy.

Further, the way that study measures (cardio)-metabolic health is itself multi-dimensional:

> Using the blood pressure, triglyceride, cholesterol, glucose, insulin resistance and C-reactive protein data, population frequencies/percentages of metabolically healthy versus unhealthy individuals were stratified by BMI.

https://www.nature.com/articles/ijo201617

I think we may need to admit that weight is a low cost and highly visible variable which is a poor proxy for actual health and as in business, optimizing for the wrong metric will eventually lead to dysfunction.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#84

Jesus christ, why is nature quoting a psychologist in an article about biology? > However, some researchers worry that these drugs play into some societies’ obsession with being thin. Body size isn’t always a good predictor of health. “I’m really hesitant to be excited about something that I think is potentially harmful from a weight stigma perspective”

Psychology is an epiphenomenon of biology.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#85
post #40

Earlier quoted context omitted.

It's like treating an addiction by telling the addict "it's ok to have some, just pinkie swear you won't overdo it." People who are obese or grossly obese often aren't just eating a "little extra" here and there. Imagine more like "extra pizza a day" or "eat a cake once a week because that seems like a good idea".

The amount of calories to add an extra 50 lbs isn't that crazy. It's around 300 calories a day. So more like 1 *slice* of pizza extra. That is why weight loss is hard to achieve. If you are hungry, it's hard to--over an entire day--avoid eating 300 extra calories.

... nah.

1Kg of human fat is around 8000kcals give or take. 50lbs is 22Kg. 176000kcal. It's 586x "extra slices of pizza", almost two years of overeating every day.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#86
post #79

> I believe that everyone, even the skinny folks, should be on GLP1 drugs for the longevity effects. Are you for real? Serious question.

I mean, if you have perfect bloodwork and a marvel movie body probably not necessary but otherwise yes. Heart disease, hypertension, high cholesterol, colon cancer rates are rising amongst everyone, even thin people. These drugs positively impact indicators of these things in everyone. Longevity makers have been betting on metformin for a long time and these drugs are like a supercharged metformin

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#88
post #79

> I believe that everyone, even the skinny folks, should be on GLP1 drugs for the longevity effects. Are you for real? Serious question.

I'm unfamiliar with the research around GLP1 drugs, but I my past reading about the long-term effects of metformin led me to a similar conclusion. Unfortunately, metformin causes me severe gastrointestinal issues that don't resolve themselves after a few weeks.

There are lots of surprising findings w/r/t pharmaceuticals if you start really digging. Lots of missed opportunity for overall improvement in the human condition that aren't being exploited.

Re: ‘Breakthrough’ obesity drugs that have stunned researchers

#89
post #83

Earlier quoted context omitted.

Helping obese people lose weight is unidimensionally a good thing

The article specifically points out that the link between weight and health on its own is in question: > Some researchers also worry that by offering a weight solution in societies that prize thinness, these drugs could also inadvertently reinforce the disputed link between excess weight and health. One study found that nearly 30% of people who are considered obese are metabolically healthy. The abstract from that ar…

Maybe that paper just shows that BMI isn’t the best metric. For example, would the results look different if the participants were stratified by bodyfat%?
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