目前尚无关于每日使用瑞他曲肽的研究。我并非断言这是既定事实，但该领域一些资深专家提出了合理的理论。由于瑞他曲肽是一种胰高血糖素激动剂，因此将其与赛玛进行比较毫无意义。您可以搜索 runningFNP 的相关文章。SVT810E said:
丽塔需要经历高峰和低谷吗？
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你说的有一定道理（虽然我觉得你本意是想说更高的平均浓度）。如果必须二选一，比如每周10毫克和每周两次每次5毫克，那么你的观点成立。但是，如果可以自由选择每周两次每次5.8毫克（而不是每周一次10毫克），那么你的观点就不成立了。MFGamesta said:
如果受限于可用的总毫克数，那么你的观点是正确的。如果受限于某个最大剂量（例如为了避免副作用），但可以无限量地获取产品，那么分次服用实际上可以达到更高的平均浓度，同时还能避免副作用。
zpped said:
To expand on this a little more, GLP-1 (and GIP) agonism could be described as "helping you eat less." The proper analysis is far more complex, but that's probably the dominant effect. Meanwhile, glucagon agonism could be described as "helping you burn more energy," which is also an enormous oversimplification.
We don't really know what the response curve for TDEE vs glucagon looks like, though. If it turns out that curve is fairly linear then split dosing VS weekly dosing would lead to similar results for glucagon agonism. If it turns out that the curve is non-linear then split dosing VS weekly dosing could actually lead to very different results.
The sema daily vs weekly results are very interesting, of course.
Quoted the wrong dude. My bad.SVT810E said:
Yes,tubby said:
for other to have a more intuitive understanding...
A linear response curve is like a bucket with a hole in it. As long as your putting water in faster than it is leaking out, it doesn't matter as there will be water in the bucket.
A non linear curve is like hammering in a nail into hard wood. You can tap on the nail forever and not make any progress until you actually hit it very hard.
There is no doubt that the purpose of large multinational or national drug companies is to make money, just like any other business. And the way to do that is to make drugs with high profit margins and sell them in large volumes. Sometimes optimisation of profit will entail higher profit and prices and lower volumes and sometimes the other direction depending on the market. Generally most of the best profit is early before generics become an option.tubby said:
But purely profit based motives are not the sole factor in drug development and marketing, they have to convince Doctors and often governments ( who are often large purchasers or who negotiate local pricing in exchange for approval or subsidy ) that their drugs are effective , safe, and often that they offer cost benefits to the alternatives. And now they also need to convince customers directly of this as well with direct to consumer marketing ( this does not exist in Aus but does in the US.) or media releases that are effectively prewritten newspaper or magazine or website articles that editors are very happy to publish for little effort.
In some ways GLP drugs are a bit unusual in that there is a bit of competition now, and competition from the superior drug tirzepatide has severely damaged semaglutide's position, and there will be a lot more competition in the future as more of the many GLP's in development make it through. So this aspect of capitalism is actually working well in this case. Prices of GLP's in china have very recently been dropped substantially in response to local legitimate alternatives, so while the west has not yet seen huge price drops I think it is inevitable sooner or later.
So producing research that shows a drugs effectiveness is superior is incredibly important . A few studies showing better weight loss from tirzepatide were enough to displace semaglutide from its market leading position despite it having first mover advantage. Those few studies resulted in billions of dollars of sales.
Producing GLP's that show good or better weight loss with less side effects is also super important. A study showing similar weight loss with less side effects could put a drug at the top of the market quite quickly. Even though the initial tirzepatide studies did not really show lower side effects clinicians and online opinion said it did and eventually the research did as well, which has certainly helped it become the most popular GLP.
I wonder whether it might even be worthwhile them doing studies on variable frequency dosing if needed to show lower side effects, or lower dropout rates for a given amount of weight loss, the differences in weight loss and side effects between tirzepatide and semaglutide are not huge but those few percent differences hit novo nordisk pretty hard financially.
I am aware of some very dubious behaviour of drug companies, fund ten studies and only publish the 5 that show benefits and bury the others. I am not certain it would be quite as easy with the GLP research where the major trials are publicised in advance and possible results discussed by investment sites even before results are available. In the case of drugs like these with such extreme public interest, and extreme financial interest , there is definitely some strong incentives for the companies to be seen as doing the right thing, simply because being caught out could have severe financial and public reputation consequences. And the amounts of money involved are enormous making all sorts of risk management serious issues.
From purely subjective experience of Sema, tirz and reta. Side effects are definitely related to peaks ( hitting the nail hard ) in level, the timing correlates perfectly with how long a dose takes to be absorbed and get to peak levels after a subcutaneous injection - about 24 hours or so. So nausea, gi side effects in general and any malaise or illness response or food aversion responses.zpped said:
Effects on hunger are a bit influenced by peak levels, especially if nausea or food aversion responses are present , this was very obvious with semaglutide but much less so with the others, but I never found any real difference in how hungry I was or how much I actually ate on a given day relative to when the last dose was, so I would say they are determined by both peak and probably more importantly baseline levels.
Weight loss effects are going to be determined by area under the curve or the sum of doses over a week, just because weight responses being delayed and summed are going to average out the drug effects over time anyway.
From all of that I really do not think there is going to be a difference to frequent or weekly dosing in weight loss effects, unless frequent dosing allows a higher overall weekly dose, if higher once a week doses cause problematic side effects.
That's what I used to think too: There surely must be redundant checks and balances in place to keep this whole endeavor honest. Surely, regulators are looking out for the interest of the patients. But then you see so many examples where that aspect has been gamed and dangerous drugs have been approved and sold for years, only to be pulled later when the few remaining checks in the system that are functioning properly finally catch a safety signal, causing the whole fraud to blow up (e.g. Vioxx). And then the post-mortem analysis shows that fraud and suppression was committed openly within the pharma company to ensure that doctors didn't get the information they needed that would have allowed them to stand in the way.lessthanhalf said:
And when you combine that with the enormous arrogance and hubris of most doctors, it makes for the perfect storm as they confident assert these perceived checks and balances. Then these same doctors belittle the "quacks" that dare to question them and the system that they're a part of because surely after all those years in medical school and equipped with their superior intellects they'd be in a position to see if fraud was happening (despite history demonstrating that is generally not the case).
Half lifes are real and the cravings at 5.5-6 days happen. Both tirz and Reta benefit substantially from 84 hour injection intervals in my studies with more than 75 people on them for >6 months. Yeah I’m one of the few that actually does research and keeps records
ironbull said:
Trevor Bachmeyer — Grokipedia
Trevor Bachmeyer (born circa 1973) is an American former licensed chiropractor (license number DC 29377) whose license was revoked effective July 8, 2020, by the California Board of Chiropractic Exami
grokipedia.com
This statement by the unlicensed chiropractor ( a field that has some pretty pseudoscientific beliefs attached to it ) is just fundamentally ignorant of basic pharmacology, and is completely opposite to my personal experiences and those of a lot of people on this forum who have used more often than weekly doses to reduce side effects but maintain the important effects like hunger suppression and weight loss. With the exception of antibiotics, where peak levels are actually useful, all drugs that I can think of benefit from more stable blood levels, rather than the dodgy concept of hitting receptors hard. Maybe some chemo drugs as well, but struggling to think of anything else.
This guy is packed full of rhetoric.RetCurious said:
lessthanhalf said:
Completely agree.
no better way to shut down a conversation that just attack the character of the speaker and not deal with the content of what he says. especially when he backs up his statements without actual studies.. did you go and read the studies he mentions.. feels like covid science debates all over again.. your not qualified to have an opinon.. are you doctor?? bla bla blalessthanhalf said:
yes its designed for a large dose to saturate receptors and then wear off during the end off the week allowing receptor sensitivity.. reason they designed the half life and clinical studies around this protocol.. but of course everyone knows betterzpped said:
ironbull said:
Calling him an unlicensed chiropractor isn't wrong, but it's not accurate... his license was revoked by the state. That's not a direct attack on his character but rather his credibility as an expert. Him wrongly referring to himself as a doctor is a character flaw.
The rest of the quoted post addresses the content of what he says.
ironbull said:
Clearly you've got some passion on this subject and for Trevor Bachmeyer with ~1/4 of your posts here being on this thread.
ironbull said:
This is still not correct, but don't let that get in the way. Funny in your linked video, Trevor is giving an opinion contrary to the studies you mentioned today, but I guess you accept he knows better and isn't included in the "everyone knows better" camp.
if you actually want to discuss the data be happy to. just not gonna get into arguing a logically fallacy of ad hominem attacks .. i have looked at the data so I don't know where your getting your conclusions from.. especially since the clinical trials are all designed around one shot a week.. lol - i also have personal experience doing daily shots and going back to one shot a week and how my body reacted and how i lost sensitivity so fast doing daily microshots..
ironbull said:
There are lots of ways to split dose a conventional once a week shot without taking them every day.
What constitutes a microshot in terms of milligrams?
I don't have a dog in the fight, but why not, it's a rain day/week.
ironbull said:
Saying he isn't a doctor is neither a logical fallacy, nor a character attack, it's an objective fact based on the evidence that has been presented online.
He wrongly and potentially fraudulently refers to himself as a "doctor" (medical expert) when he isn't (he was a Doctor of Chiropractic) and lost his license. He apparently lost his license in CA and lives in TX, both require you to have a valid license to refer to yourself as "Doctor" and both state you must clearly say you're a chiropractic doctor (vs a medical doctor). If we're throwing latin around, using him as a source would be "argumentum ad verecundiam."
An ad hominem attack would be discrediting your post based on the abundance of grammatical and syntactical errors, implying that your lack of high school level articulation is evidence that your position is inferior. That attacks your deficiencies rather than the position itself. See the difference?
Wait, are you an employee of one of the Big Pharma companies? What do you mean by "your studies?"Wardor said:
Chiropractors do have pseudoscientific beliefs, the system of medicine they operate on believes that you can alter the function of internal organs by manipulating joints. Now they do other stuff that is more like physiotherapy which is scientifically valid, but using a system of thought for medical therapy that is not based on a scientific understanding of how the body functions, is by definition pseudoscience, and that reduces the credibility of his arguments. I do not know much about the education process of chiropractors and to what degree they study pharmacology or if they prescribe medications. I would be very concerned about anyone prescribing medication with such basic misunderstandings of pharmacology, it is not something that is OK to ever get wrong. Presenting himself as an expert in the pharmacology of these drugs is not appropriate for the qualifications he has even if licensed.
Being delicenced, not sure why, but still calling himself a doctor also reduces his credibility in general. If his license was revoked by the state , that is often due to unacceptable behaviour, but could just be from not paying fees but this is a bit unusual to let those types of registrations lapse for no good reason.
My main criticism is his pharmacology is plain wrong. All the GLP drugs have a half life of about a week, so that a week after the first dose, minimum blood levels are half their peak, and after 4 weeks that minimum level ( just before the next dose ) is quite a bit higher, and at that point there is still a lot of activation of the receptors. At standard full doses of GLP drugs the GLP receptors are very close to fully saturated at peak drug levels, or at their maximum possible response level, which is why increasing doses above that does not cause much extra weight loss as shown by the 7.2mg and 16mg semaglutide studies. At minimum drug levels there is still a lot of receptor activation, drastically more ( by orders of magnitude ) than would ever occur from endogenous GLP. So just for example at peak levels you might have 90% glp-1 agonism and at minimum you might have somewhere between 70-80% ( it is non linear ) . This does not give the receptors a rest and prevent tolerance. Most people, but not all, do not experience fluctuations in hunger over the week suggesting that the gap between minimum and maximum levels is not noticeable.
From the long term follow up studies on semaglutide, tolerance to the weight loss effects did not occur over 5 years. So if therapy was continued, the graph of weight loss was a flat line for 5 years, if tolerance occurred this weight would trend up over time, and it does not. There is evidence for some types of tolerance early in GLP therapy, in the first few months to gastric emptying and gastrointestinal side effects. If tolerance is not present in 5 years of follow up it is not going to suddenly develop from minor changes in peak to minimum drug levels.
The concept of side effects being maximal at peak blood levels of the drug is just basic pharmacology, and applies to a very large number of drugs, it is not in any way unique to GLP's. The idea that lower peaks and higher minimum drug levels that would occur from daily rather than weekly doses could cause more side effects is just plain incorrect pharmacology, and requires not understanding how drugs and receptors work. For most drugs dosing is determined by aiming for as stable blood levels as possible while keeping dosing frequency reasonable, as asking people to take drugs 4 times a day usually results in people missing doses. And this is definitely the case for medications aimed at metabolic or cardiac processes, - you want stability not variation. Taking GLP medications once a week provides quite stable receptor agonism for most people, except for few who get hungry on day 6.
And I have formally studied pharmacology. ( a fair while ago ) I do not claim to be an expert but have at least read most of the papers published on GLP drug development and treatment for obesity, but not every single review or all the ones about different operations and outcomes on GLP's as there are thousands of them.
From purely personal experience taking ozempic, I could not tolerate weekly doses above 0.5mg. Even that caused some nausea and malaise and any time I tried to increase it to 0.6mg, I felt pretty awful, barely wanting to get out of bed for a couple of days afterwards. Yet I tolerated 0.22mg every second day with less adverse effects than I got from 0.5mg once a week. Which adds to 0.8mg per week. This experience is completely consistent with the pharmacology and a lot of people on this forum, who found split dosing to be an effective way of reducing side effects, and the opposite of those claims made.
Being delicenced, not sure why, but still calling himself a doctor also reduces his credibility in general. If his license was revoked by the state , that is often due to unacceptable behaviour, but could just be from not paying fees but this is a bit unusual to let those types of registrations lapse for no good reason.
My main criticism is his pharmacology is plain wrong. All the GLP drugs have a half life of about a week, so that a week after the first dose, minimum blood levels are half their peak, and after 4 weeks that minimum level ( just before the next dose ) is quite a bit higher, and at that point there is still a lot of activation of the receptors. At standard full doses of GLP drugs the GLP receptors are very close to fully saturated at peak drug levels, or at their maximum possible response level, which is why increasing doses above that does not cause much extra weight loss as shown by the 7.2mg and 16mg semaglutide studies. At minimum drug levels there is still a lot of receptor activation, drastically more ( by orders of magnitude ) than would ever occur from endogenous GLP. So just for example at peak levels you might have 90% glp-1 agonism and at minimum you might have somewhere between 70-80% ( it is non linear ) . This does not give the receptors a rest and prevent tolerance. Most people, but not all, do not experience fluctuations in hunger over the week suggesting that the gap between minimum and maximum levels is not noticeable.
From the long term follow up studies on semaglutide, tolerance to the weight loss effects did not occur over 5 years. So if therapy was continued, the graph of weight loss was a flat line for 5 years, if tolerance occurred this weight would trend up over time, and it does not. There is evidence for some types of tolerance early in GLP therapy, in the first few months to gastric emptying and gastrointestinal side effects. If tolerance is not present in 5 years of follow up it is not going to suddenly develop from minor changes in peak to minimum drug levels.
The concept of side effects being maximal at peak blood levels of the drug is just basic pharmacology, and applies to a very large number of drugs, it is not in any way unique to GLP's. The idea that lower peaks and higher minimum drug levels that would occur from daily rather than weekly doses could cause more side effects is just plain incorrect pharmacology, and requires not understanding how drugs and receptors work. For most drugs dosing is determined by aiming for as stable blood levels as possible while keeping dosing frequency reasonable, as asking people to take drugs 4 times a day usually results in people missing doses. And this is definitely the case for medications aimed at metabolic or cardiac processes, - you want stability not variation. Taking GLP medications once a week provides quite stable receptor agonism for most people, except for few who get hungry on day 6.
And I have formally studied pharmacology. ( a fair while ago ) I do not claim to be an expert but have at least read most of the papers published on GLP drug development and treatment for obesity, but not every single review or all the ones about different operations and outcomes on GLP's as there are thousands of them.
From purely personal experience taking ozempic, I could not tolerate weekly doses above 0.5mg. Even that caused some nausea and malaise and any time I tried to increase it to 0.6mg, I felt pretty awful, barely wanting to get out of bed for a couple of days afterwards. Yet I tolerated 0.22mg every second day with less adverse effects than I got from 0.5mg once a week. Which adds to 0.8mg per week. This experience is completely consistent with the pharmacology and a lot of people on this forum, who found split dosing to be an effective way of reducing side effects, and the opposite of those claims made.
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