6 ms·

my favorite part of ozempic is that it settled the debate on calorie reduction.

parpfish 2y ago
Did it? The drugs clearly lead to reduced appetite, therefore reduced calories. But do we know that the drugs aren’t also causing other important metabolic changes?
- nradov 2y ago
  The drugs seem to cause a small increase in resting heart rate. Whether that is due to metabolic or neurologic changes (or something else) isn't completely clear.
- bitmasher9 2y ago
  Was it ever really a debate? There’s tons of experimental evidence that shows calorie reduction leads to weight loss, even without pharmaceuticals. The Ozempic data can be explained simply by this factor. There doesn’t seem to be enough data fluctuation between the two sets to indicate a significant set of unknown variables impacting the data.
  - parpfish 2y ago
    yeah, but do ozempic et al only rely on calorie reduction? i find it hard to believe that hormones only affect one thing in isolation. it may be doing something like a) suppressing appetite to reduce caloric intake AND b) shielding against a lowered metabolism due to calorie restriction.
    - tonymet 2y ago
      If there is predominant evidence of significant calorie reduction leading to weight loss, and no evidence of the metabolic hypothesis , what should be our conclusion?
- gnkyfrg 2y ago
  [dead]
- spondylosaurus 2y ago
  It's not even appetite per se; GLP-1s regulate blood sugar for more sustained levels, which is upstream of appetite. Safe to say that blood sugar impacts a bunch of other stuff too.
- tonymet 2y ago
  Occam's razor
- paulpauper 2y ago
  I think it confers some metabolic boost, but more data is needed
arcticbull 2y ago
The debate has never been "will consuming less calories than you expend make you lose weight" -- the debate has been "will just telling people to consume less calories, patting yourself on the back and calling it a day make them lose weight." The latter was settled in a 2023 cohort study that showed doing is completely ineffective. [1] There's been tons of data on this. The scientific consensus has been pretty clear for a hundred years, but nobody wanted to listen. Probably in part because there was no good solution before. [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC10407685/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10407685/
- Aurornis 2y ago
  > The debate has never been "will consuming less calories than you expend make you lose weight" If you missed the whole "calories in, calories out" debate, consider yourself lucky. The comment above isn't helpful, but there really was a period of time where the topic du jour among health influencers was debating that calories didn't explain weight gain or loss. It played into the popular idea that blame for the obesity epidemic rested squarely on the food industry and "chemicals" in our food. At one point, I had a podcast-obsessed coworker who tried to tell us all that even when he ate 1000 calories per day he couldn't lose weight. He had a long list of influencers and podcasters who supported this claim. The CICO debate was especially popular among influencers pushing their own diet. Debating CICO was a convenient gateway to selling people your special diet that supposedly avoids the "bad" calories and replaces them with "good" calories, making you lose weight.
  - arcticbull 2y ago
    Ah, gotcha. For what it's worth CICO sucks because (1) nobody can stick to it, ever (2) humans are awful at estimating their calories in, studies show only 1/5 of people can properly estimate the calorie content of their food [1] and (3) your metabolism slows down in response to, specifically, caloric restriction diets and your hunger rises which makes it difficult to estimate your calories out without indirect calorimetry. Yes, CICO works in a lab, and for some weird people. It's a matter of thermodynamics. However you are a far more complex system than a coal powered furnace. And yes certain types of food will be more or less satiating and may influence the amount of total calories you consume. It's really really hard to overeat if you just eat lean protein, for instance. CICO is, in practice, a tool that is roughly impossible for most people to leverage to lose a meaningful amount of weight and keep it off. Which brings us back to the difference between maintaining a persistent caloric deficit -- and instructing people to do so. [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC3719184/ https://pmc.ncbi.nlm.nih.gov/articles/PMC3719184/
phil21 2y ago
Unfortunately it didn’t. Seems to have actually emboldened the “CICO isn’t a thing” crowd even more. The amount of woo-woo “science” in laymen communities on the subject is utterly astounding considering the evidence directly in front of them. Check out the various subreddits for a casual glimpse - anyone saying stuff like “the primary method of action is eating less” is downvoted and the woo woo “metabolism” or “hormones” stuff is upvoted and celebrated. In the end I think there is a lot of weird guilt around overeating I never really understood existed before. I lost 100lbs using Mounjaro but never once thought it was anything other than me eating too much and moving too little while I was obese. It’s just a lot of damn work and willpower for me to change that. Tirzepatide was simply a performance enhancing drug for my diet that finally put me over escape velocity to make lifestyle changes that so far have stuck for a couple years now.
- kjkjadksj 2y ago
  I’ve been flamed here on HN for asserting CICO is valid. In truth there are few scientists among us.
SkyPuncher 2y ago
I don't think it was ever really a debate. "Reduce calories" is about as useful as "exercise more", "sit less", "drink less", etc, etc. All are obviously good, but for various reasons it can be hard for people to achieve them. GLP-1's basically take the "how" out of the equation. Take this drug, eat less without fighting your own desires.
- s1artibartfast 2y ago
  All of them are essential as an objective to implement or improve the how.
- tonymet 2y ago
  there are plenty of people who claim that no amount of calorie reduction results in weight loss. Often it's people who are claiming to eat starvation amounts of food while gaining weight. Of course researchers have known it was delusional, but the belief persisted in pop culture. Ozempic is putting that to rest. this is a case where more personal / colloquial / folk evidence was needed to convince people.
  - titanomachy 2y ago
    I doubt that the people who believe that obese people somehow violate the first law of thermodynamics will be convinced to change their mind now, just because Ozempic became a thing. They will probably just misunderstand how the drug works.
- paulpauper 2y ago
  Yes, "eat less" is the answer, but this is harder to do yeah if your metabolism is slow or always being hungry. this drugs makes it easier to eat less and hence lose weight .
rs999gti 2y ago
> settled the debate on calorie reduction. Really? Because GLP1s reduce hunger and food cravings, less of those means less eating, less eating means less calories. The drug just makes people involuntarily fast, it has no thermogenic of lipolysis abilities.
jncfhnb 2y ago
Ozempic tends to change not just the total number of calories but also the timing and the cravings for shitty food. Calories in / calories used is NOT a complete model because different foods can have different caloric retention. The most extreme example being corn that comes out entirely undigested. Further, shittier foods that the body craves most are also the least satiating over the longer term. Reducing calories is three or four steps removed from the actual problem. Like arguing the problem is organ failure when in the first order problem is that you got shot. You have to deal with the wound; and you have to deal with the blood loss. That will, in turn, address the organ failure.
tonymet 2y ago
I should get more karma for this sub thread

Did it? The drugs clearly lead to reduced appetite, therefore reduced calories. But do we know that the drugs aren’t also causing other important metabolic changes?

nradov 2y ago
The drugs seem to cause a small increase in resting heart rate. Whether that is due to metabolic or neurologic changes (or something else) isn't completely clear.
bitmasher9 2y ago
Was it ever really a debate? There’s tons of experimental evidence that shows calorie reduction leads to weight loss, even without pharmaceuticals. The Ozempic data can be explained simply by this factor. There doesn’t seem to be enough data fluctuation between the two sets to indicate a significant set of unknown variables impacting the data.
- parpfish 2y ago
  yeah, but do ozempic et al only rely on calorie reduction? i find it hard to believe that hormones only affect one thing in isolation. it may be doing something like a) suppressing appetite to reduce caloric intake AND b) shielding against a lowered metabolism due to calorie restriction.
  - tonymet 2y ago
    If there is predominant evidence of significant calorie reduction leading to weight loss, and no evidence of the metabolic hypothesis , what should be our conclusion?
gnkyfrg 2y ago
[dead]
spondylosaurus 2y ago
It's not even appetite per se; GLP-1s regulate blood sugar for more sustained levels, which is upstream of appetite. Safe to say that blood sugar impacts a bunch of other stuff too.
tonymet 2y ago
Occam's razor
paulpauper 2y ago
I think it confers some metabolic boost, but more data is needed

arcticbull 2y ago

The debate has never been "will consuming less calories than you expend make you lose weight" -- the debate has been "will just telling people to consume less calories, patting yourself on the back and calling it a day make them lose weight." The latter was settled in a 2023 cohort study that showed doing is completely ineffective. [1] There's been tons of data on this. The scientific consensus has been pretty clear for a hundred years, but nobody wanted to listen. Probably in part because there was no good solution before. [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC10407685/ https://pmc.ncbi.nlm.nih.gov/articles/PMC10407685/

Aurornis 2y ago
> The debate has never been "will consuming less calories than you expend make you lose weight" If you missed the whole "calories in, calories out" debate, consider yourself lucky. The comment above isn't helpful, but there really was a period of time where the topic du jour among health influencers was debating that calories didn't explain weight gain or loss. It played into the popular idea that blame for the obesity epidemic rested squarely on the food industry and "chemicals" in our food. At one point, I had a podcast-obsessed coworker who tried to tell us all that even when he ate 1000 calories per day he couldn't lose weight. He had a long list of influencers and podcasters who supported this claim. The CICO debate was especially popular among influencers pushing their own diet. Debating CICO was a convenient gateway to selling people your special diet that supposedly avoids the "bad" calories and replaces them with "good" calories, making you lose weight.
- arcticbull 2y ago
  Ah, gotcha. For what it's worth CICO sucks because (1) nobody can stick to it, ever (2) humans are awful at estimating their calories in, studies show only 1/5 of people can properly estimate the calorie content of their food [1] and (3) your metabolism slows down in response to, specifically, caloric restriction diets and your hunger rises which makes it difficult to estimate your calories out without indirect calorimetry. Yes, CICO works in a lab, and for some weird people. It's a matter of thermodynamics. However you are a far more complex system than a coal powered furnace. And yes certain types of food will be more or less satiating and may influence the amount of total calories you consume. It's really really hard to overeat if you just eat lean protein, for instance. CICO is, in practice, a tool that is roughly impossible for most people to leverage to lose a meaningful amount of weight and keep it off. Which brings us back to the difference between maintaining a persistent caloric deficit -- and instructing people to do so. [1] https://pmc.ncbi.nlm.nih.gov/articles/PMC3719184/ https://pmc.ncbi.nlm.nih.gov/articles/PMC3719184/

phil21 2y ago

Unfortunately it didn’t. Seems to have actually emboldened the “CICO isn’t a thing” crowd even more. The amount of woo-woo “science” in laymen communities on the subject is utterly astounding considering the evidence directly in front of them. Check out the various subreddits for a casual glimpse - anyone saying stuff like “the primary method of action is eating less” is downvoted and the woo woo “metabolism” or “hormones” stuff is upvoted and celebrated. In the end I think there is a lot of weird guilt around overeating I never really understood existed before. I lost 100lbs using Mounjaro but never once thought it was anything other than me eating too much and moving too little while I was obese. It’s just a lot of damn work and willpower for me to change that. Tirzepatide was simply a performance enhancing drug for my diet that finally put me over escape velocity to make lifestyle changes that so far have stuck for a couple years now.

kjkjadksj 2y ago
I’ve been flamed here on HN for asserting CICO is valid. In truth there are few scientists among us.

SkyPuncher 2y ago

I don't think it was ever really a debate. "Reduce calories" is about as useful as "exercise more", "sit less", "drink less", etc, etc. All are obviously good, but for various reasons it can be hard for people to achieve them. GLP-1's basically take the "how" out of the equation. Take this drug, eat less without fighting your own desires.

s1artibartfast 2y ago
All of them are essential as an objective to implement or improve the how.
tonymet 2y ago
there are plenty of people who claim that no amount of calorie reduction results in weight loss. Often it's people who are claiming to eat starvation amounts of food while gaining weight. Of course researchers have known it was delusional, but the belief persisted in pop culture. Ozempic is putting that to rest. this is a case where more personal / colloquial / folk evidence was needed to convince people.
- titanomachy 2y ago
  I doubt that the people who believe that obese people somehow violate the first law of thermodynamics will be convinced to change their mind now, just because Ozempic became a thing. They will probably just misunderstand how the drug works.
paulpauper 2y ago
Yes, "eat less" is the answer, but this is harder to do yeah if your metabolism is slow or always being hungry. this drugs makes it easier to eat less and hence lose weight .

rs999gti 2y ago

> settled the debate on calorie reduction. Really? Because GLP1s reduce hunger and food cravings, less of those means less eating, less eating means less calories. The drug just makes people involuntarily fast, it has no thermogenic of lipolysis abilities.

jncfhnb 2y ago

Ozempic tends to change not just the total number of calories but also the timing and the cravings for shitty food. Calories in / calories used is NOT a complete model because different foods can have different caloric retention. The most extreme example being corn that comes out entirely undigested. Further, shittier foods that the body craves most are also the least satiating over the longer term. Reducing calories is three or four steps removed from the actual problem. Like arguing the problem is organ failure when in the first order problem is that you got shot. You have to deal with the wound; and you have to deal with the blood loss. That will, in turn, address the organ failure.

tonymet 2y ago

I should get more karma for this sub thread