📌难道🇷🇪🇹🇦就该是这样吗⁉️❓

[Smiter]

A proper logician would understand the inherently irrational/unreasonable/illogical fault plaguing most "clinical" studies and thus, the indisputably flawed "evidence" resulting from them. "Clinical" studies are often performed in controlled, "clinical" settings with predetermined variables, and many variables are discounted for ease. Real-life settings are undeniably different from such clinical settings. Additionally, they ignore empirical evidence from real life if it doesn't gel with their "laboratory"-derived "facts", when it ought to be done the other way around.

For example, for decades now, the scam about saturated fat being a malignant evil and plant-based/vegan diets being a panacea has been pervading mainstream discourse. Yet, the original four Blue Zones: Okinawa, Ikaria, Sardinia, Costa Rica, where people have longevity and long healthspans have traditional diets rich in saturated fat, low in seed oils, high in red meat, low in simple sugars.. In fact, in Okinawa, the Blue Zone with the longest lifespan of them all, they even had lower seafood consumption than the rest of Japan. Even more tellingly, after 2000, Westernization changed Okinawan diets, and their lifespans decreased. On top of that, they discard the French Paradox, Israeli Paradox, and refuse to consider the unhealthiness of the largest population of a historically vegetarian ethnicity in India.

In this scenario, a bunch of people have testified to using split dosing because it helps them with greater appetite suppression, and staving off food noise. Yet, some people claim a lack of clinical evidence as reason enough to dismiss these assertions. That same flawed principle is used in other contexts too, where it is equally wrong because it fails to account for a very important fact:

ABSCENCE OF ANY EVIDENCE ( EVEN CLINICAL ) IS NOT EVIDENCE OF ABSCENCE.

 

[Smiter]

I started January 9 at once a week and have lost 40lbs. I read about the half life way back before starting and way before joining here. Staying with the once a week deal.

I totally understand the half life deal. See above. I’ll continue on my once a week.

Oh, I have no issues with your understanding of the half-life concept. How could I? I don't even know you. You can definitely continue as you see fit. Why would I ever have a problem with that? On the contrary, I wish you the very best of success in all your endeavors.

 

[longestyards]

I can't understand why anyone would dose once a week. The half life is six days. Receptor desensitization is a myth. Split dosing is super effective for me.

That is what they’re doing in the trials. The drug was designed to be used and dosed once a week. I think it’s probably a good idea to follow the protocol that the scientists who made the drug have developed for it. I’m not saying twice isn’t as good or inferior, that we don’t know yet. I’m just saying it was designed with once a week dosage in mind that’s why the half life is six days and the dosage is usually taken 4 weeks before changing it up (from 2mg to 4mg for instance). For instance if you dose once a week at 2mg by the fourth week you’ll have 4mg in your body and that means your body is fine with 4mg so you can start dosing 4mg etc.

 

[BNLFL]

Ah yes, the youngsters always needing to be correct and know everything in 2 months.

 

[birdwhacker]

That is what they’re doing in the trials. The drug was designed to be used and dosed once a week.

I understand this line of reasoning and I won't fault you for it. I'm well aware of the half-life, what doses the trials used, and their reasoning behind that. I have been deeply invested in pharmacology for more than a decade at this point, and I think you're looking at the whole thing with a certain level of naïvete that I don't think is neccessary. You should have a little more faith in your own reasoning.

Trusting the word of the clinical studies to be the Alpha and Omega dictating your research is sort of like saying that the guidelines from the DMV are the only proper way to drive a car. Once you get in the grass, you may find that your own instincts serve you better.

A proper logician would understand the inherently irrational/unreasonable/illogical fault plaguing most "clinical" studies and thus, the indisputably flawed "evidence" resulting from them.

What he said, but phrased more eloquently.

Ah yes, the youngsters always needing to be correct and know everything in 2 months.

Hey leave me out of this BNLFL! No idea why he went off on you

The "no evidence" guy just gets it for being cringe.

 

[BNLFL]

Hey leave me out of this BNLFL! No idea why he went off on you

Hey, I actually like you.

 

[birdwhacker]

Hey, I actually like you.

Same, BNLFL. What's the profile pic from btw?

 

[BNLFL]

Same, BNLFL. What's the profile pic from btw?

Old Road Warrior 2 from 1981, part of the Mad Max stuff. One of the guys on the big car forum I'm a admin on made it for me. Honest question, where you born yet?

 

[Smiter]

Hey leave me out of this BNLFL! No idea why he went off on you

The "no evidence" guy just gets it for being cringe.

Ah yes, the youngsters always needing to be correct and know everything in 2 months.

Hey, both of you, leave me out of that. I wasn't targeting anybody in particular. It was purely a discussion of the concept of "studies and evidence". In fact, if anything, I was targeting a discussion on another thread where the colossal reliance on such "evidence" was truly egregious.

But, @BNLFL, thanks for calling me a youngster. NGL, it does feel good.

About knowing everything in two months, I wish. That would be utopia for me.

That is what they’re doing in the trials. The drug was designed to be used and dosed once a week. I think it’s probably a good idea to follow the protocol that the scientists who made the drug have developed for it. I’m not saying twice isn’t as good or inferior, that we don’t know yet. I’m just saying it was designed with once a week dosage in mind that’s why the half life is six days and the dosage is usually taken 4 weeks before changing it up (from 2mg to 4mg for instance). For instance if you dose once a week at 2mg by the fourth week you’ll have 4mg in your body and that means your body is fine with 4mg so you can start dosing 4mg etc.

Errr... yeah, if you begin with a 2mg weekly dose, based on a half-life of 6 days, on day 30, you will end up with 3.1mg in the body. Even on the GLplotter, it shows 3.07mg.

But also, are you sure that the various trials underway are being conducted by the people who made Retatrutide? I find that unlikely, even if it was a relevant argument. Saying that a tool should only be used the way its inventor wanted it to be used would be logically flawed, don't you think?

 

[birdwhacker]

Old Road Warrior 2 from 1981, part of the Mad Max stuff. One of the guys on the big car forum I'm a admin on made it for me. Honest question, where you born yet?

Thought it was Mad Max. The 2015 video game is a guilty pleasure of mine.

I was born in '99. Honest question, did you tank the housing market?

 

[Smiter]

Old Road Warrior 2 from 1981, part of the Mad Max stuff. One of the guys on the big car forum I'm a admin on made it for me. Honest question, where you born yet?

I wasn't, and never was a fan of the Road warrior franchise. I, in fact, thought first that your profile picture was of Jason Voorhees.

 

[Smiter]

Speaking of dosages, I had more of a stomach upset issue with the first dose of 1mg than the second dose of 1.5mg. In fact, I even lost more weight after the first dose than with the second one, and had more suppression of appetite with the first 1mg dose. Did any of you experience the same? This too contributed to my idea about changing my dosing. I think I'm too large for the 1mg dose.

 

[GLP1Pharmacist]

He asked for a reason, I gave one. N's of one is less reliable than actual evidence. 6 day half life also really leads to weekly making better sense for most. All said you do you, go daily.

 

[Smiter]

He asked for a reason, I gave one. N's of one is less reliable than actual evidence. 6 day half life also really leads to weekly making better sense for most. All said you do you, go daily.

Do you think that the reason people choose weekly single doses is because they are convinced that it is the right way, or is it because they see that this is the way that most people are doing it because of one mainstream case?

 

[GLP1Pharmacist]

Hard to honestly tell, probably more to do with the drug companies trying to make it as easy as possible. Weekly sells better than daily or even twice a week. There is at least one stating once a month is coming.

 

[Smiter]

Hard to honestly tell, probably more to do with the drug companies trying to make it as easy as possible. Weekly sells better than daily or even twice a week. There is at least one stating once a month is coming.

See now that's another issue. Split dosing doesnt mean double dose, just more smaller shots. But yes, I totally agree, the future will bring oral, infrequent dosing

 

[lessthanhalf]

The biggest advantage in split dosing at this point in the process, low doses and starting, especially with some side effects at low doses, is to be able to increase doses more quickly if wanted, and to do it with lower risks of severe or prolonged side effects.

Compared to a single weekly dose of 2mg, 2 1mg doses 3.5 days apart, are going to produce lower peak drug levels, and peak drug levels are usually where side effects are worst, and it will take less time for blood levels to drop to around pre dose levels, where presumably side effects were not an issue, than for a single larger dose where peaks will be higher, and it will take longer for levels to fall back down to pre dose levels, so side effects are likely to be worse and last longer.

Whether you want to stay on split dosing longer term depends a lot on side effects and doses. If you are trying to balance side effects against effects it can be useful or if you find it wears off after 5 or 6 days, but switching to weekly is reasonable once dose is stable just for convenience.

 

[Smiter]

The biggest advantage in split dosing at this point in the process, low doses and starting, especially with some side effects at low doses, is to be able to increase doses more quickly if wanted, and to do it with lower risks of severe or prolonged side effects.

Compared to a single weekly dose of 2mg, 2 1mg doses 3.5 days apart, are going to produce lower peak drug levels, and peak drug levels are usually where side effects are worst, and it will take less time for blood levels to drop to around pre dose levels, where presumably side effects were not an issue, than for a single larger dose where peaks will be higher, and it will take longer for levels to fall back down to pre dose levels, so side effects are likely to be worse and last longer.

Whether you want to stay on split dosing longer term depends a lot on side effects and doses. If you are trying to balance side effects against effects it can be useful or if you find it wears off after 5 or 6 days, but switching to weekly is reasonable once dose is stable just for convenience.

That's excellent news that will feature into my calculations for sure. Thanks a ton.

 

[ThatNextGril]

I wasn't, and never was a fan of the Road warrior franchise. I, in fact, thought first that your profile picture was of Jason Voorhees.

ngl so did I. oops!

 

[lessthanhalf]

A proper logician would understand the inherently irrational/unreasonable/illogical fault plaguing most "clinical" studies and thus, the indisputably flawed "evidence" resulting from them. "Clinical" studies are often performed in controlled, "clinical" settings with predetermined variables, and many variables are discounted for ease. Real-life settings are undeniably different from such clinical settings. Additionally, they ignore empirical evidence from real life if it doesn't gel with their "laboratory"-derived "facts", when it ought to be done the other way around.

For example, for decades now, the scam about saturated fat being a malignant evil and plant-based/vegan diets being a panacea has been pervading mainstream discourse. Yet, the original four Blue Zones: Okinawa, Ikaria, Sardinia, Costa Rica, where people have longevity and long healthspans have traditional diets rich in saturated fat, low in seed oils, high in red meat, low in simple sugars.. In fact, in Okinawa, the Blue Zone with the longest lifespan of them all, they even had lower seafood consumption than the rest of Japan. Even more tellingly, after 2000, Westernization changed Okinawan diets, and their lifespans decreased. On top of that, they discard the French Paradox, Israeli Paradox, and refuse to consider the unhealthiness of the largest population of a historically vegetarian ethnicity in India.

In this scenario, a bunch of people have testified to using split dosing because it helps them with greater appetite suppression, and staving off food noise. Yet, some people claim a lack of clinical evidence as reason enough to dismiss these assertions. That same flawed principle is used in other contexts too, where it is equally wrong because it fails to account for a very important fact:

ABSCENCE OF ANY EVIDENCE ( EVEN CLINICAL ) IS NOT EVIDENCE OF ABSCENCE.

I disagree with a great deal of this.

Medical research apart from purely economic concerns, which are not irrelevant, is about finding the best possible ways of determining true outcomes with reliable information out of noisy messy data. This is very hard to do. And there are lots of different ways to try to do this, each which produces different types and qualities of data, some of which are more reliable than others. And it really matters, peoples lives depend on getting it right.

In general the highest possible quality of data that exists in medicine is a placebo ( or alternate drug ) controlled , double blind, prospective clinical trial. Where neither the researcher or the subjects knows if they are getting the drug or placebo. This matters as placebo responses can be astonishing, for example placebo morphine in acute severe pain works, not as well as actual morphine, but far better than anyone would guess. And researcher bias matters as well. You can go as far as triple blinding so the data is randomised so even the data analysis is blind but this is not very common. The patients in the two groups need to be selected to match as closely as possible. And then the drugs are given and you find out what happens, analyse the results and determine if your new drug or other treatment worked or not and apply statistical methods to determine how likely it is to be a true effect or a chance effect. The larger the number of patients and the longer the time usually result in higher quality data. The amount of thought , time , and evolution of this process is significant, gradually over time more and more flaws in the process have been found and removed, and in general modern studies have fewer methodological flaws

The other method is to gather up all those controlled trials and add up the results to make an effectively much bigger study or a meta analysis with systematic review. If the trials are similar enough then the quality of result from these can be even higher than the individual trials, but recently paper mills have been cranking these papers out by the millions which have highly variable quality, making it hard to determine which ones are the good ones.

Any drug that gets approved for human use in modern times has gone through these trials, and this process is as good as humans can get to absolute truth, where the data is noisy. So in general the results of this type of trial is as reliable as it is possible to get, and is considered accurate enough to bet peoples lives on. As that is usually exactly what is at stake.

因此，这类试验被认为是研究的黄金标准，其结果值得信赖，前提是这些结果由具备足够技能和知识的人员解读。问题在于，这些试验的范围有限，而且必须如此，以便尽可能控制变量，确保信息的可靠性。但通常情况下，它们无法解答所有问题，或者结果可能不适用于特定范围之外的情况，而临床决策往往需要在缺乏这些信息的情况下做出。有时，这些试验的结果后来被证明是错误的，即使一项研究有非常充分的统计证据，表明结果仅有1%的概率是偶然的，它仍然会有1%的概率出错。但这已经是目前所能达到的最佳水平了。

除了这类试验之外，还有大量其他方法可以获取与健康相关的信息，但这些方法的结果可信度各不相同。

基于人群的研究确实能够提供信息，但它们通常无法提供足以证明疾病因果关系或特定疗法有效的证据。许多前瞻性对照临床试验的结果与基于人群的研究预期结果截然不同。目前关于饮食与健康的最佳信息是，地中海饮食或类似饮食方式与最低的健康风险相关。我并非专家，无法解释这些最新研究中使用的流程。

就可信度而言，实证研究通常处于另一个极端，即它能否被证明是正确的，或者我们能尽可能接近正确答案。观察者对患者治疗的体验是有效的，对他们而言是真实的，就像患者对治疗的体验一样。问题在于这些数据能否可靠地应用于其他人。常识告诉我们答案是肯定的。但这里存在一些混杂变量，而临床试验正竭力避免这些变量。首先是安慰剂效应，无论是来自患者还是观察者。在这种情况下，患者或疾病本身的反应可能并不典型。如果我是科学哲学专家，我相信我还能补充更多。

一般来说，经验证据并非毫无用处，所有医生都会使用并依赖它，而且随着时间的推移，重复的证据确实会使其更加可靠。但是，基于经验证据的医疗疗法也包括一些使用了数千年的方法，例如放血疗法，因此它当然也可能提供错误或不真实的信息。通常情况下，除非别无他法，否则经验证据的质量不足以作为决定人命的依据。