What do you tell your Doctor

[lessthanhalf]

“Statins would be expected to be less effective than GLP1s”

This is not supported by current evidence.

Event reduction magnitude:

Statins: ~22–25% MACE reduction per 1 mmol/L LDL drop.

PCSK9 inhibitors: similar per ApoB reduction.

GLP-1 RAs: ~12–20% MACE reduction.

Statins have:

Larger and more consistent mortality benefit.

Decades of data.

Clear dose–response relationship.

GLP-1 drugs are excellent therapies, but they are not superior to statins for atherosclerotic event prevention.

There is no serious cardiology body that considers GLP-1 a substitute for lipid lowering in established ASCVD.

It does state that there are circumstances where GLP therapy might be superior overall to statin therapy in very specific circumstances, but in the real world almost everyone would be better on both in those circumstances. As by definition both diabetes and severe obesity carry high absolute cardiovascular risk.

“If forced to choose, most would be better off choosing GLP1 over statin”

This depends entirely on the patient phenotype.

In:

Established coronary disease

High CAC

High LDL

Statin benefit is foundational and larger.

In:

Severe obesity without high LDL

Diabetes with metabolic syndrome

GLP-1 may provide broader metabolic benefit.

Assessing mortality effects of statin therapy is complex, mortality is always going to be a lower number than the number of heart attacks prevented, so showing statistically significant effects is always going to be harder, and requires very long term studies and very large numbers of patients. Glp effects on mortality are only demonstrated in those with established cardiovascular disease and diabetics, not in the general population of obese persons at this time, but this is likely to be proven eventually but might take a decade or so.

MACE is major atherosclerotic cardiovascular event - heart attack, stroke etc

Direct comparison (roughly) of statins vs glp-1 agonists from large scale meta analyses

Therapy Relative MACE Reduction Relative All-Cause Mortality Reduction

Statins (per 1 mmol/L LDL drop) ~22–25% ~10–20%

GLP-1 RA (semaglutide range) ~15–20% ~8–12%

If LDL is high this reduction is per drop of 1mmol/L , so for example my pretreatment LDL was 4.7 and post treatment 1.5, a drop of 3.2 so roughly triple that effect. Which would make the effect on MACE reduction 66-75% and mortality 30-60%, 3 to 5 times the effect of GLP's. This is a huge difference in effectiveness between statins vs glp's, and most people needing lipid lowering therapies are going to have higher LDL levels that can be dropped by more than 1mmol/l.

 

[Zydeceltico]

This depends entirely on the patient phenotype.

In:

Established coronary disease

High CAC

High LDL

Statin benefit is foundational and larger.

In:

Severe obesity without high LDL

Diabetes with metabolic syndrome

GLP-1 may provide broader metabolic benefit.

Or in my case of crossing over both phenotypes, I am using a GLP1 and a statin and have religiously tracked my labs throughout the process including a stent placement due to 80% occlusion on the LCX.

I attest that they (GLP1 and statin) are BOTH necessary and work very well TOGETHER.

Amazing how sometimes inclusion produces better results than exclusion.

 

[tubby]

“Statins would be expected to be less effective than GLP1s”

This is not supported by current evidence.

Event reduction magnitude:

Statins: ~22–25% MACE reduction per 1 mmol/L LDL drop.

PCSK9 inhibitors: similar per ApoB reduction.

GLP-1 RAs: ~12–20% MACE reduction.

Statins have:

Larger and more consistent mortality benefit.

Decades of data.

Clear dose–response relationship.

GLP-1 drugs are excellent therapies, but they are not superior to statins for atherosclerotic event prevention.

There is no serious cardiology body that considers GLP-1 a substitute for lipid lowering in established ASCVD.

It does state that there are circumstances where GLP therapy might be superior overall to statin therapy in very specific circumstances, but in the real world almost everyone would be better on both in those circumstances. As by definition both diabetes and severe obesity carry high absolute cardiovascular risk.

“If forced to choose, most would be better off choosing GLP1 over statin”

This depends entirely on the patient phenotype.

In:

Established coronary disease

High CAC

High LDL

Statin benefit is foundational and larger.

In:

Severe obesity without high LDL

Diabetes with metabolic syndrome

GLP-1 may provide broader metabolic benefit.

Assessing mortality effects of statin therapy is complex, mortality is always going to be a lower number than the number of heart attacks prevented, so showing statistically significant effects is always going to be harder, and requires very long term studies and very large numbers of patients. Glp effects on mortality are only demonstrated in those with established cardiovascular disease and diabetics, not in the general population of obese persons at this time, but this is likely to be proven eventually but might take a decade or so.

MACE is major atherosclerotic cardiovascular event - heart attack, stroke etc

Direct comparison (roughly) of statins vs glp-1 agonists from large scale meta analyses

Therapy Relative MACE Reduction Relative All-Cause Mortality Reduction

Statins (per 1 mmol/L LDL drop) ~22–25% ~10–20%

GLP-1 RA (semaglutide range) ~15–20% ~8–12%

If LDL is high this reduction is per drop of 1mmol/L , so for example my pretreatment LDL was 4.7 and post treatment 1.5, a drop of 3.2 so roughly triple that effect. Which would make the effect on MACE reduction 66-75% and mortality 30-60%, 3 to 5 times the effect of GLP's. This is a huge difference in effectiveness between statins vs glp's, and most people needing lipid lowering therapies are going to have higher LDL levels that can be dropped by more than 1mmol/l.

I appreciate your very respectful response. I had hoped that I had written my response in plain enough English that a chatbot wouldn't be needed to digest it, but I'll admit it did get a little long. Chatbots are notoriously bad at logical deduction. They're great at finding and rephrasing sentiment that they find.

I'd agree with your chatbot that many studies exist that measure the effect of lipid lowering on cardiac and mortality outcomes and essentially no studies exist for GLP1s in that regard. However, that doesn't answer the question of which might be superior, it just answer the question of which has been studied more.

Let me restate and summarize the meat of my analysis, since perhaps by including the background and context, my core argument got lost:

Start with reviewing Figure 1 here:

https://jamanetwork.com/journals/jamacardiology/fullarticle/2775559

Note which conditions have the highest hazard ratios for cardiovascular health. You'll see that obesity, smoking, diabetes, metabolic syndrome, and hypertension all matter way more than LDL does when it comes to being drivers of heart disease. That's not to say LDL doesn't matter, just that these other factors matter way more when statistical analysis is performed.

In going through that list I think you'll conclude (without any further analysis) that GLPs are much better suited to treat most of the conditions on that list with the highest hazard ratios. That doesn't settle the matter definitively, of course, but I think it's a more honest attempt at answering the question than looking to see which drug class has been studied more (the chatbot approach).

 

[80s.diver]

So doctors in the US and scammers. I'm from Australia where we did have free medical. But not anymore. Our consults start at $75AUD then we apply for a rebate from Medicare. So ends up costing $35-$40 for every doctor visit.

I keep smoking weed and glps a secret from my doctor. Affects job prospects and other things...

Do the doctors report the weed and glp1 usage or is it Medicare. Just curious on how it affects job prospects, is nothiing private anymore.

 

[tubby]

Not to mention the studies that show that lifespan increases from statins can be surprisingly low or non-existent. So still a lot a room for debate and "further research" for Joe Blow being on statins vs. other interventions (not that they are mutually exclusive):

The median increase in lifespan was 3.2 days for primary prevention and 4.1 days for secondary prevention. OTOH, preventing even one person from getting a major event (using statins, BP meds, smoking cessation, and/or lifestyle interventions) can be a big deal:

As mostly a vegetarian (pescatarian), I am a big fan of plant-based diets and somewhat a fan of the late Dr. John McDougal ("Dr. Potato"). Like the peptide pusher Dr. Seeds, the potato pusher Dr. McDougall had a great personality for Youtube. But even with his strict vegan diet, McDougall may have lived longer if he didn't dismiss statins or big-time exercise, especially since he had genetic factors (having had a massive stroke at age 18). We'll never know. His numbers were good without statins, but his LDL was not aggressively low like under 55 (or even sub-40):

McDougall lived to age 77, which was 59 years after the stroke that gave him a permanent limp. For his patients, McDougall was unfortunately against GLPs, did not give enough attention to exercise, and his starch-based vegan diet didn't allow for healthy fats (which the American Heart Association didn't like, favoring instead a Mediterranean-style, plant-based diet). He was also against the use of supplements. But I don't see the harm in taking collagen on a mostly vegetarian diet.

Dr. Seeds would say injectable peptides are better than oral supplements, as peptides are corrective (give instructions/signals rather than just building blocks). But high-potency natto seems better for removal of existing plaque ( up to 36 percent reduction in 26 weeks, with some blood thinning, for better or worse). Natto also has synergistic effects with vit K2 (MK7). Peptides like SS-31 and hexarelin may be better for prevention for some cardiovascular factors, though not as much as GLPs.

My personal belief when it comes to lipids is that high LDL, low HDL, or high triglycerides are proxies for deeper underlying health problems (often diet/lifestyle-related). I think there's much greater value in using them as indicators to help you determine if lifestyle changes you've made are on the right or wrong track VS trying to pharmaceutically target them. If I take a statin to bring my LDL down "within range" that makes my doctor happy, but it takes away my ability to use the metric to assess dietary changes I'm making. For example, if I cut bread and pasta out of my diet and see my triglycerides drop by 50 mg/dL, I suspect that's going to be more impactful in terms of addressing the underlying problem.

I think another mistake that gets made is fixating on LDL more strongly than other key labs. Doctors fixate on LDL because it prompts them to make a prescribing decision, but in trying to infer health status from your labs, HDL and triglycerides are superior metrics and more strongly correlated to heart disease than LDL, so it's important to watch all rather than fixating on one in isolation. For example, let's say a low-carb diet bumps your LDL up from 110 mg/dL to 140 mg/dL, but also bumps your HDL up from 30 mg/dL to 70 mg/dL, while dropping your triglycerides from 130 mg/dL to 90 mg/dL. Your doctor might freak out about your "high" LDL "moving in the wrong direction," and miss the bigger picture.

 

[Zydeceltico]

I appreciate your very respectful response. I had hoped that I had written my response in plain enough English that a chatbot wouldn't be needed to digest it, but I'll admit it did get a little long. Chatbots are notoriously bad at logical deduction. They're great at finding and rephrasing sentiment that they find.

I'd agree with your chatbot that many studies exist that measure the effect of lipid lowering on cardiac and mortality outcomes and essentially no studies exist for GLP1s in that regard. However, that doesn't answer the question of which might be superior, it just answer the question of which has been studied more.

Let me restate and summarize the meat of my analysis, since perhaps by including the background and context, my core argument got lost:

Start with reviewing Figure 1 here:

https://jamanetwork.com/journals/jamacardiology/fullarticle/2775559

Note which conditions have the highest hazard ratios for cardiovascular health. You'll see that obesity, smoking, diabetes, metabolic syndrome, and hypertension all matter way more than LDL does when it comes to being drivers of heart disease. That's not to say LDL doesn't matter, just that these other factors matter way more when statistical analysis is performed.

In going through that list I think you'll conclude (without any further analysis) that GLPs are much better suited to treat most of the conditions on that list with the highest hazard ratios. That doesn't settle the matter definitively, of course, but I think it's a more honest attempt at answering the question than looking to see which drug class has been studied more (the chatbot approach).

Since I'm using both GLP and statin and know that I have atherosclerosis, don't smoke, don't drink, don't have diabetes, metabolic syndrome or hypertension but do have stubbornly low HDL (35), should I just trust your word here and drop the statin as it is apparently inconsequential?

You are arguing that stance fairly prolifically and apparently without the aid of a chat bot which makes you much more convincing so.........how much cred should we put in your words?

 

[tracylynn]

If you tell them you are taking gray market drugs, they can put you on prescription monitoring and it stays with you forever. Then every time you go to a ER or doctor they treat you like a drug seeker. Don’t give them a reason.

This actually made me think about my past surgery (I have dealt with a lot of large kidney stones and have had to go in to have them removed). Totally did not think about the peptides I'm taking and the marks from my daily injections on my upper thighs. (Klow is easier there)

Later I thought about that surgery crew and that they could very well think I'm on drugs with all of those purple areas. lol

 

[tubby]

Since I'm using both GLP and statin and know that I have atherosclerosis, don't smoke, don't drink, don't have diabetes, metabolic syndrome or hypertension but do have stubbornly low HDL (35), should I just trust your word here and drop the statin as it is apparently inconsequential?

You are arguing that stance fairly prolifically and apparently without the aid of a chat bot which makes you much more convincing so.........how much cred should we put in your words?

1: I never said you or anyone else should stop taking statins.

2: I'm some random guy on the internet. Talk to your doctor for medical advice. This is a theoretical/conceptual discussion, not medical advice.

If this conversation leads you to develop a deeper interest in the topic of lipids that's a win. I would never presume to tell someone else what they personally should or shouldn't do.

 

[tubby]

Since I'm using both GLP and statin and know that I have atherosclerosis, don't smoke, don't drink, don't have diabetes, metabolic syndrome or hypertension but do have stubbornly low HDL (35), should I just trust your word here and drop the statin as it is apparently inconsequential?

You are arguing that stance fairly prolifically and apparently without the aid of a chat bot which makes you much more convincing so.........how much cred should we put in your words?

To expand on that just a little more:

My primary beef with statins is that (just like many other major pharma products) there was a fair amount of grift and deceit involved in gaming regulatory approval. They designed studies in a way where people who did poorly on statins (side effects) were either excluded or washed out from the studies and in doing so were able to show lower adverse event rates for their products than would be expected in the real world. In addition, by focusing on intermediate markers (LDL levels and cardiac events) rather than more objective markers (all cause mortality) they were able to make their products appear more effective in benefiting overall health than they actually were. They got "busted" later on (via studies like @Calm Logic pointed out) where lifespan increases on statins were found to be largely negligible, but generally very little has changed as a result of that.

They succeeded in creating the perception that statins have such a minor cost and such a major benefit that just about everyone should be on them and in doing so we have an environment where rather than being highly selective about who they prescribe statins to, many doctors will recommend them as soon as they see someone's LDL trend above a certain level. That would be the part that I would personally object to. I think a much more comprehensive analysis should be performed on a person prior to putting them on a statin for the rest of their life. LDL-C is a very sloppy marker to begin with, since it's just a very crude estimation of your actual LDL level rather than a direct measure of it. Measuring ApoB or LDL-P to validate an LDL-C result would be the bare minimum testing I'd personally think a doctor should do before considering a statin and many doctors can't even be bothered to do that.

And even then, cardiology has to answer for why it is that long-term studies relating cholesterol to all-cause mortality show that people with slightly elevated cholesterol levels tend to live longer on average than those at lower level (without resorting to their logically inconsistent "reverse causality" argument/excuse). They're just so myopically fixated on the cardiovascular system that it's seemingly blinded them to the bigger picture. It's great if you can reduce cardiac events, but if you haven't made any meaningful improvements in lifespan or all cause mortality, one really needs to step back and question why exactly that is rather than sticking your head in the sand and ignoring that result.

 

[joseblo]

My personal belief when it comes to lipids is that high LDL, low HDL, or high triglycerides are proxies for deeper underlying health problems (often diet/lifestyle-related). I think there's much greater value in using them as indicators to help you determine if lifestyle changes you've made are on the right or wrong track VS trying to pharmaceutically target them. If I take a statin to bring my LDL down "within range" that makes my doctor happy, but it takes away my ability to use the metric to assess dietary changes I'm making. For example, if I cut bread and pasta out of my diet and see my triglycerides drop by 50 mg/dL, I suspect that's going to be more impactful in terms of addressing the underlying problem.

I think another mistake that gets made is fixating on LDL more strongly than other key labs. Doctors fixate on LDL because it prompts them to make a prescribing decision, but in trying to infer health status from your labs, HDL and triglycerides are superior metrics and more strongly correlated to heart disease than LDL, so it's important to watch all rather than fixating on one in isolation. For example, let's say a low-carb diet bumps your LDL up from 110 mg/dL to 140 mg/dL, but also bumps your HDL up from 30 mg/dL to 70 mg/dL, while dropping your triglycerides from 130 mg/dL to 90 mg/dL. Your doctor might freak out about your "high" LDL "moving in the wrong direction," and miss the bigger picture.

I'll agree with you that the initial statin approvals were based on theory, and the all cause mortality can even be lower (though there are sampling problems, if you don't correct for income/existing conditions), but there are also genetic sources of cholesterol. Much of the cholesterol in your blood is made by your liver, which is how statins work (by interfering with that). To give an example both my dad and I have rising total cholesterol with age, well over 300 at 40yo independent of diet/exercise. Mom and brother eating/exercising the same are half that. Statins cut it by more than half, and HDL is still over 60. I'd rather not take it, and with Reta that's a possibility. I'll probably test low/no dose, but I won't let the total go up to 300 again.

 

[tubby]

I'll agree with you that the initial statin approvals were based on theory, and the all cause mortality can even be lower (though there are sampling problems, if you don't correct for income/existing conditions), but there are also genetic sources of cholesterol. Much of the cholesterol in your blood is made by your liver, which is how statins work (by interfering with that). To give an example both my dad and I have rising total cholesterol with age, well over 300 at 40yo independent of diet/exercise. Mom and brother eating/exercising the same are half that. Statins cut it by more than half, and HDL is still over 60. I'd rather not take it, and with Reta that's a possibility. I'll probably test low/no dose, but I won't let the total go up to 300 again.

To be clear, I'm not anti-statin. I'm just opposed to when they're indiscriminately prescribed without properly weighing the pros and cons. I believe they offer a real benefit to certain groups of people. Just as I'd shake my head at someone with a BMI of 26 starting retatrutide to lose weight, I'd similarly shake my head at a lazy doctor who is either failing to fully evaluate the patient in front of them before prescribing a statin or is too poorly informed to properly conduct that analysis.

Also, it's worth noting that if one buys into lipid lowering therapies, statins aren't the only game in town. PCSK9 inhibitors are another option. I'm not as well informed on them so couldn't lay out the pros and cons. I'll only note that unlike statins, PCSK9 inhibitors at least make sense conceptually.

With statins we're playing this game where we think we know better than our liver what needs to be done. When we say someone has a high "cholesterol" level what we're really saying is that the amount of cholesterol floating around in the bloodstream inside of lipoproteins is high. The cholesterol itself is largely irrelevant. It's just a convenient way of estimating the concentration of LDL particles floating around in your bloodstream (since that's one of the particles that shuttles cholesterol around your body). That's why a cardiologist would prefer a marker like ApoB over LDC-C. ApoB is a more accurate measure of the lipoprotein concentration (independent of cholesterol or particle size). Cholesterol is just the red herring that we first observed many years ago and has remained a convenient way to estimate LDL. And I know that probably sounds controversial, but it's not: Any cardiologist will agree with me on that point.

So when statins reduce the amount of cholesterol being produced in the liver, what they're really doing is choking out your body's overall cholesterol supply and your liver is pulling LDL particles more rapidly back into the liver (and out of your bloodstream) as a means of coping with the limited supply of cholesterol. It's a clever hack to reduce LDL population in the bloodstream. What remains an open question is if your body had a good reason for previously circulating so much cholesterol around before you started taking the drug. Maybe it did, maybe it didn't. We know so little about our bodies that it's really impossible to say.

And that's why I say PCSK9 inhibitors at first glance appear to be a more elegant option. Since the actual goal of lipid-lowering therapies is to reduce LDL population, PCSK9 inhibitors more directly accomplish that VS statins which use the indirect approach of tanking your body's cholesterol production.

 

[Zydeceltico]

ApoB is a more accurate measure of the lipoprotein concentration (independent of cholesterol or particle size).

My ApoB June 6, 2025 was 148 (before statin and tirz).

August 25, 2025 (3 months of tirz) ApoB was 121

January 16, 2026 four months of statin it was 55.

 

[lessthanhalf]

We seem to be thinking about these things from different points of view.

in response to this

"I'd agree with your chatbot that many studies exist that measure the effect of lipid lowering on cardiac and mortality outcomes and essentially no studies exist for GLP1s in that regard. However, that doesn't answer the question of which might be superior, it just answer the question of which has been studied more."

What you are saying is exactly what is the case , but your conclusion is exactly incorrect. The definition of a superior treatment is the one with the best evidence in real world randomised controlled clinical trials of changes in measurable outcomes. This is the highest standard of evidence that exists. It might be correct that GLP medications will acquire superior evidence for prevention of cardiovascular disease in the future, but until that research is done, decisions need to be based on the actual real evidence that exists, not on what anyone thinks or believes might be the case on the basis of research that has not been done.

Statins are used because they are proven just about more than any class of medication to work, to reduce cardiovascular disease and as stated in my previous post , mortality. And yes there are other lipid lowering therapies but statins are the first step. The others are the second and third steps.

Thankfully doctors usually make decisions about treatment based on evidence not wishful thinking. And all I am concerned about is people using wishful thinking rather than the science or medical advice to guide treatments that could be needed to save lives.

Critically analysing scientific studies is genuinely hard, and realistically requires many years of study , usually by people who are very bright to start with. Doctorates are not that easy to get and they are just the starter qualification. I do not claim to be at that level. The understanding of modes of thinking required to not make errors of interpretation is just difficult to achieve.

I generally do not make statements of fact in my posts unless I have verified them to be correct, using external sources. Chatgpt is a good quick way of checking facts, and the way I use it , with elaborate prompting, it is reliable. And overall I am extremely impressed with its simulation of logic, I know it really does not understand logical thought processes , but through the magic of large language models it can produce statements of logic superior to my understanding, just from having absorbed so much writing, which is kind of impressive. Checking each of the dozens of "facts" in your post would take hours to days to verify, and is not worth it. ( no offence intended, it would take a long time )

You did not address any of the criticisms of your statements of fact in the previous response, but the bigger problem is one of logic or approach. This is its conclusion about your argument. Please note I subjected my post to the same criticism.

" Where their reasoning goes wrong

The main errors are:

Treating hazard ratios as proof of relative causal importance.

Ignoring cumulative LDL exposure.

Ignoring Mendelian randomization evidence.

Ignoring dose–response relationship of ApoB lowering.

Overstating GLP-1 relative benefit.

Framing LDL lowering as crude and nonspecific when it is actually mechanistically validated.

The tone suggests skepticism of “AHA/cardiologist literature,” but the overwhelming body of lipid science is not narrow specialty opinion — it is cross-validated across genetics, pathology, imaging, and randomized trials."

Most of your statements have some science behind them, but you make large claims from limited evidence.

I make few claims or statements of fact, and ensure they are correct before posting ( or at least try hard ) . Given the concern I have is people abandoning proven treatments for unproven ones, there is no reasonable scientific criticism that can be made of that point. Just opinion.

 

[tubby]

My ApoB June 6, 2025 was 148 (before statin and tirz).

August 25, 2025 (3 months of tirz) ApoB was 121

January 16, 2026 four months of statin it was 55.

And that's the result I and everyone else would expect. Statins are good at getting LDL (and ApoB) down. GLPs are good at reducing weight and A1c.

 

[tubby]

I'll start with the part that you bolded, since I think that means you feel it carries the most weight:

The definition of a superior treatment is the one with the best evidence in real world randomised controlled clinical trials of changes in measurable outcomes. This is the highest standard of evidence that exists.

I respect that you're demanding rigorous studies be conducted before a course of action is taken, but we're years (if not decades) away from having data on long-term cardiac impact for GLPs. Yes, if you are working as a clinician in a clinic it would be irresponsible for you to recommend GLPs for a cardiac benefit that hasn't been clinically observed (yet). When you're having an intellectual debate on the internet, it's kind of disingenuous to try to shut it down this way, though. I've already agreed with you on this point (that GLPs haven't been studied in this particular context clinically), so I'm not sure why you raise it again. We're in full agreement here that it would be irresponsible for a medical doctor to recommend GLPs for a cardiac benefit.

Chatgpt is a good quick way of checking facts, and the way I use it , with elaborate prompting, it is reliable.

I'd test that a little more if I were you. I have a (deeply religious) friend who enjoys arguing religious topics with ChatGPT. He has argued with it and "convinced" it of all sorts of wild and zany things, which he loves to point out while trying to sell his religion to me. Chatbots are largely sycophants when it comes to any debate that involves intellection reasoning. I agree they might be useful as a more effective search engine or to look something up quickly, but you'll get yourself in real trouble if you rely on their output for anything reputational.

Checking each of the dozens of "facts" in your post would take hours to days to verify, and is not worth it.

I've spent quite a bit of time trying to dig in and make sense of this subject precisely because it is generally written about in such a confusing and contradictory manner, which bothered me. When I found conclusions that appeared to be faulty I did my best to dig into literature and articles to resolve those faulty conclusions. If modern cardiology is in fact a coherent and logically consistent framework then they should have answers to the objections that I raised. They don't. Or at least I haven't found them yet, despite trying really hard to find them. Part of my interest in debating this is because maybe someday I will find someone who can resolve the logical contradictions that seem to exist in their models and treatment methodologies. That's why I raise them in the manner that I do.

I can respect that you don't want to put time into verifying all of them and that's fine. Just pick one or two, dig in and see where you end up. I suspect that when you realize that I'm not full of crap on that one or two that you'll be intrigued that not only do such gaps exist in their field, but they're strangely not the least bit bothered by them, nor do they appear to have any interest in conducting studies to resolve them. It's a truly perplexing state of affairs.

The main errors are:

Treating hazard ratios as proof of relative causal importance.

Ignoring cumulative LDL exposure.

Ignoring Mendelian randomization evidence.

Ignoring dose–response relationship of ApoB lowering.

Overstating GLP-1 relative benefit.

I think you're copying and pasting here without putting though into whether the chatbot output makes sense or not, but I'll address these since you're implying that I'm dodging them. To the extent they were raised I think I just skipped answering them before because they seemed self-evident.

Hazard ratios: These are the factors that most strongly correlate to cardiac risk. I'm not sure where else a person would start with such an analysis. This is the list doctors currently use to tell their patients that they should lose weight, stop smoking, and better control their diabetes in order to improve their cardiovascular risk profile. To suggest that it's clinically valid for doctors to do that, but suddenly invalid when we talk about a GLP doing it is a really odd stance for you to take. That was why I asked you to sanity check your chatbot output before pasting it in this conversation.

Cumulative LDL exposure: I acknowledged this from the beginning. Go back and read my ping-pong analogy in which I contextualize it.

Mendelian randomization evidence: Not sure where this fits in so can't speak to it.

Dose-response of ApoB lowering: Nowhere have I denied this. The closest I came to critiquing it was referencing the point @Calm Logic brought up about increased lifespan results for statin use being rather disappointing. My point there was that if statins are as effective as they're sold to us as being that lifespan studies on them should have produced stronger results than they did and that is a point that needs to be answered.

Overstating GLP-1 relative benefit: Really???

I would enjoy having an honest conversation/debate with you, as you seem well-informed and like you're genuinely interested in the topic, but I will ask this of you going forward: Feel free to use ChatGPT as much as you want to tear apart my logic in any way that it can; however, please refrain from copy/pasting its output here, unless you have sanity checked its responses to ensure that they're reasonable and only include the parts that are . It's list of "main errors" is a great example of why such a check is important. I try to limit my own use of chatbots because I believe using them as a crutch over time negatively affects one's own reasoning abilities and gives one a false sense of confidence (due to their sycophantic nature).

 

[Calm Logic]

Let me restate and summarize the meat of my analysis, since perhaps by including the background and context, my core argument got lost:

Start with reviewing Figure 1 here:

https://jamanetwork.com/journals/jamacardiology/fullarticle/2775559

Note which conditions have the highest hazard ratios for cardiovascular health. You'll see that obesity, smoking, diabetes, metabolic syndrome, and hypertension all matter way more than LDL does when it comes to being drivers of heart disease. That's not to say LDL doesn't matter, just that these other factors matter way more when statistical analysis is performed.

In going through that list I think you'll conclude (without any further analysis) that GLPs are much better suited to treat most of the conditions on that list with the highest hazard ratios. That doesn't settle the matter definitively, of course, but I think it's a more honest attempt at answering the question than looking to see which drug class has been studied more (the chatbot approach).

That figure is the most interesting thing I have seen in a long time:

 

[tubby]

That figure is the most interesting thing I have seen in a long time:

What's beautiful about that figure is that the hazard ratio is calculated using standard deviations rather than some other arbitrarily selected number (that could be used to skew the result).

It also demonstrates that their current model of how plaque progression works is extremely questionable. They fixate on LDL concentration (which is definitely a factor), but if it were the primary factor, we'd expect it to have a much higher hazard ratio. When we see that other factors dominate that tells us that it's much more likely that those other factors are what are enabling plaque accumulation to occur.

Perhaps under normal conditions LDL very rarely sticks to arterial walls, but when those walls are weakened by some other stressor then LDL can stick. And the hazard ratios seem to support that. If hypertension (high blood pressure) is a stronger factor than LDL, that makes sense, since higher pressure could conceivably put arterial walls at greater risk of LDL sticking to them (and accumulating). If diabetes (high blood sugar) is a stronger risk factor than LDL, that makes sense since glucose can be damaging and at higher levels is likely causing damage to arterial walls that put them at greater risk of LDL sticking to them.

That's not to say LDL isn't a factor, just that the chart I shared suggests plaque deposits are being largely enabled by other factors. If that's true then one's first line of defense should be to eliminate those other factors (obesity, diabetes, smoking, hypertension). LDL reduction can still be valuable too, obviously. It's just that since it can't safely be driven to zero, it would be foolish to primarily focus on LDL, while ignoring obesity, diabetes, smoking, and hypertension. It would be on par with setting up a fox defense system inside of your henhouse instead of just building a wall around the henhouse to keep them out.

 

[rGrain]

Did you have to go through the MOVE program and did they limit your maximum dose? That's what my doc told me I would have to do.

Yep I am doing it now and the order is made so I get official meds soon

 

[GuidoLoko]

If it became medically relevant I'd disclose everything.

Otherwise I keep it to "I'm on compounded tirz" when in reality I'm on reta. "I'm on TRT" when I long stopped going to a TRT clinic and started sourcing my own test, etc.

I'm not too worried since my doctor is laid back, knows about my recreational drug use and gives no fucks, etc., but I figure there's just not any real reason for me to explicitly mention all of the shit I'm on that isn't related to anything ongoing.

Dayum he sounds cool af! I wish I was able to have a doc like that !!

 

[Zoidberg]

I told my doctor at the VA I was on a glp1 at first and didn’t specify (Reta) . We have had a few conversations about how fucked the US healthcare system is and are on the same page.

Source conversation eventually came up and I explained to him how he was severely overpaying for his (tirz) . He didn’t believe me at first because the price was so much less . I showed him a couple vendor list and jano coa’s aaaaand now my doctor orders his own meds form china .