#21

We cannot eat ourselves out of obesity.

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#22

I’m curious about this too it doesn’t seem there’s been any definitive studies about this.I’m 71 and have generally been 20 pounds over ideal weight. I do think some is genetic when I look at the big butts of generations past in my mom’s family, and I’m shaped so much like she was, but I have spells where I just don’t have much appetite and I always lose 6 to 10 pounds then and I’ve wondered if slender people have less appetite all the time. And of course, when I do have more of an appetite, obviously I don’t have the discipline to just be hungry. As for those who are grossly overweight, there must be something wrong with how they metabolize food as don’t see how a person can eat so much to get 100 plus pounds over weight and yet I think I’ve heard that metabolism doesn’t have all that much to do with it. When I was 16, I went on a very strict diet and got down to average 115 pounds. At 5’4.5” this was the weight of most my classmates at that height, and yet I stopped having my period so some bodies must need more weight to function properly? The doctor gave me some thyroid to get it going again.

#23

It’s all very complicated. There are genetic factors, there are metabolic factors, there are gut microbiome factors.

Anyone can just eat less and move more, do that hard enough and you will get results. But different people need different levels of this to get results.

Drugs like tirzepatide, retatrutide and semaglutide completely change the game by causing people to just not crave food as much, have more self-control/willpower, improve insulin response, etc.

I’m doing research on an endogenous gut metabolite (indolepropionamide) right now and I’m finding a lot of evidence that when the upstream processes that lead to it being created are disrupted that people have lower inhibitory control leading to higher chances of obesity and other compulsive behaviors.

“The associations between the SCWT and alterations in tryptophan metabolism were replicated in the Imageomics cohort (n=970), where plasma levels of tryptophan and some microbial-derived tryptophan catabolites (indolepropionamide) were positively associated with the SCWT performance”

Crazy part is when they transplanted the gut microbes from someone who was obese to a mouse the mouse had similar inhibitor control problems: “FMT (Faecal microbiota transplantation) from individuals with obesity led to alterations in mice reversal learning.”

I’m 100% confident that we have all the tools necessary to completely cure obesity, and our repertoire of tools is only going to improve as time goes on.

#24

Oh yes I forgot about the fecal transplants - read a story of one lady gaining a lot of weight when given one from an overweight person. I wonder if it applies to energy too - I have chronic fatigue and have wondered about getting one from my nephew who has such superb energy. That’s another issue I wish more was known about - look at Trump - eats fast food, overweight, doesn’t exercise, sleeps 4-5 hours a night and goes all day and seems to feel great. Don’t mean to start anything political but he’s a prime example and it’s no fair! :slight_smile:

#25

Might work.

Rich, unlimited access to cutting edge drugs, treatments and specialists. No one really knows but I’ve heard speculation that high level officials get legal access to powerful nootropic drugs that allow them to work more effectively but it seems to age them badly.

#26

Here’s a brand new one that’s already passed a phase 1 trial and headed to phase 2. It acts like a mitochondrial uncoupler, but uses the creatine cycle to dissipate energy as heat instead of UCP1. Apparently it’s also selective for fat tissue, so it doesn’t cause the potentially massive increase in body temp seen with toxoc uncoupling drugs like DNP:

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#27

Yikes, I’ll wait to see phase 3 on that one, mitochondrial uncouplers can be very dangerous. I would be curious as to what happens when you overdose on it. Overdosing GLP1s is terrible, but they shouldn’t kill you.

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#28

It seems a lot safer than DNP.

“Chronic administration of SANA (400 mg per kg per day) to normal mice for 8 weeks showed no signs of renal or liver toxicity” (note this is very much unlike the uncoupler DNP, which kills mice at higher doses.

They aren’t going to overdose human subjects in the phase 2 or 3 trials and it’s an oral capsule, so dramatic overdosing would need to be intentional rather than accidental.

https://www.nature.com/articles/s42255-025-01311-z

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#29

Still wise to avoid until more data comes out. GLP1 agonists are already promising enough as it is imo!

Still cool to see new stuff come out.

#30

I think the new pills will make healthy weights much more achievable for everyone even a few pounds over weight. This is likely to be the biggest thing in “longevity” for the average person in the near future, and it gets people in the mental space of taking medications for health maintenance… which will lead to more interest in real longevity drugs…

From today’s Washington Post:

Ozempic 2.0 is on the way, and it could be even more transformative

Ozempic, and the class of weight loss drugs it has come to embody, has left its imprint seemingly everywhere: On the lives of millions of patients who’ve lost unprecedented amounts of weight. On grocery store shelves with new offerings explicitly catering to those taking the drugs. Even in the calculations of insurance companies studying the drugs’ effects on mortality. (Yes, there are Ozempic guides to Thanksgiving.)

For all the societal changes ushered in by GLP-1 drugs, their lofty price tags limit who can afford them. Many patients stop taking the medications after experiencing undesirable side effects. Others who could benefit have stayed on the sidelines because they don’t want to jab themselves.

A new wave of the medicine is coming that could be even more transformative for human health: pills, more potent injectables and new compounds that might have fewer side effects or could be taken just once a month.

“With this newer generation of medications, we’re not just focusing on weight loss,” said David Lau, an endocrinologist and professor emeritus at the University of Calgary Cumming School of Medicine. “We’re talking about changes beyond what you see on the scale.”

Novo Nordisk and Eli Lilly are both preparing to launch once-a-day weight loss pills by next year if the FDA approves them, as is widely expected. That would allow patients to avoid the jab of auto-injector pens with tiny needles.

“Some people are afraid of using needles and giving themselves injections,” Lau said.

Pills don’t require refrigeration — which adds cost and complexity to shipping and storing injectable medications — and there are signs that their price tags will be lower.

“What Henry Ford did with the car wasn’t to make a better car. He just made more of them and made them more accessible,” said Sean Wharton, a physician-researcher in Toronto and the lead author of two New England Journal of Medicine papers on oral GLP-1 drugs published in September. By offering more convenience at a lower cost, he said, these pills could do something similar for weight loss.

The trade-off is that pills being tested so far don’t work as well. In clinical trials stretching over a year, participants taking each drug have lost an average of about 11 to 14 percent of their body weight. That compares to about 15 to 20 percent weight loss for the most effective drugs given by injection.

Anticipation of the pills is so great that they are already included in drug price negotiations with the White House. Novo Nordisk and Eli Lilly struck deals with the Trump administration earlier this month to offer certain medications at a discount in exchange for access to Medicare, which until now has been prohibited from covering medications for weight loss. Novo Nordisk and Eli Lilly said they would offer the lowest dose of their new pills, if approved, directly to consumers for $150 a month.

História completa: Ozempic 2.0 is on the way, and it could be even more transformative

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#31

Why many people get so large?

(1) absence of education about nutrition and food preparation. This should be front and center in the grade school curriculum, as it is in some other countries
(2) social norms and bonding. If people in your family, your friends, are overweight, then there is at the least no incentive to eat healthy, and at the worst, subtle pressure to comply in order to fit in
(3) omnipresence of processed super-palatable foods that are sort of addictive
(4) a vicious cycle – being depressed, eating, getting more depressed and feeling powerless, ashamed, and then drowning those feelings by eating more food.
(5) social acceptance – people are seeing more large size models, and instead of “overweight,” or “fat” people now “have obesity.”
(6) Not a lot of societal pressure to change. On the contrary, there is money to be made by selling highly processed food, medically treating and dispensing drugs.

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