大概一年前，这还是个热门话题：服用瑞他莫昔芬（Reta）的间隔不应超过6到7天，因为它能更好地适应体内激素水平的波动。我们现在还是这么认为吗？大家的看法有改变吗？我其实不是想听个例，而是想就此展开更广泛的讨论。我知道有人一周服用2到7次……
丽塔需要经历高峰和低谷吗？
- Thread starter Peotidethrowaway
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我也很好奇这一点。我还想知道这是否仅限于reta，还是其他GLP也类似。Peotidethrowaway said:
我觉得如果目标是真正减肥，谁会在意体重波动呢？如果你每个月能减掉5磅以上，而且能承受副作用，何必画蛇添足呢？如果有些副作用你无法承受，可以按照之前的方案逐渐减少剂量，如果实在不行，可以尝试其他方法。
有些人似乎太执着于调整剂量……追求某种快感。
有些人似乎太执着于调整剂量……追求某种快感。
真的吗？我完全不知道。Habibibi said:
我更感兴趣的是分析每7天给药一次和更频繁给药的疗效对比。看来这里没人对科学讨论感兴趣。你们还是继续讨论供应商吧。我去搏击俱乐部进行更深入的讨论。
I inject once a week. Nowhere did I suggest I, or anyone else, should do otherwise. Thanks for the unsolicited lectureMFGamesta said:
I’ll go have serious conversations on more serious servers I guess.I've been doing 1mg reta every 5 days, and yep definitely peaks and valleys. The first few days I'm like "ew food," then 2 days of "I like food, but I don't need much," then on shots day (day 5) I'm ready for a cow. So, 5 days works for me, but I'm basically at maintenance weight now so I'll prob change it to 6-7 days after this week.
Oh yeah, I can link you to the trials that show they used once a weekly dosing, they're easy to find. Not much scientific discussion to be had on weekly vs daily since there are no studies on daily dosing for humans.Peotidethrowaway said:Really? I had no idea.
I’m more interested in analysis of the efficacy when dosed every 7 days vs more frequently. Guess no one is interested in a scientific discussion around these parts. Carry on with vendor discussion I guess. I’ll head over to fight club for more in depth discussion
There is at least one done on rodents for semaglutide, all it showed was that more frequent injection led to the same amount of weight loss. Rodent metabolism is weird.
You don’t want anecdotal… there are no trials ran about anything aside from FDA streamlined once weekly, as best I know.Peotidethrowaway said:Really? I had no idea.
I’m more interested in analysis of the efficacy when dosed every 7 days vs more frequently. Guess no one is interested in a scientific discussion around these parts. Carry on with vendor discussion I guess. I’ll head over to fight club for more in depth discussion
I've been dosing every 3 days it has worked very well, on weight loss all my numbers are better, lost Visceral fat too.. I have minimal peaks and valleys. But the heart rate stays higher most of the time too. I'm really hoping that's not detrimental.
I also stack/stagger tirz every 3 days the day before Reta, also down this week to 1.1ea.( 2.75 per week.)
I stack semax in there too, and Klow, periodically.
I have reached goal weight and have begun titrating down, I'm still not sure if skipping a day, vs just lowering dose would be best. I've gone from 1.3 each to 1. so effective 3mg to 2.5 per week. The day after reta is the most strong, not super great cant eat much, and fatigue.
I also stack/stagger tirz every 3 days the day before Reta, also down this week to 1.1ea.( 2.75 per week.)
I stack semax in there too, and Klow, periodically.
I have reached goal weight and have begun titrating down, I'm still not sure if skipping a day, vs just lowering dose would be best. I've gone from 1.3 each to 1. so effective 3mg to 2.5 per week. The day after reta is the most strong, not super great cant eat much, and fatigue.
The reason for weekly dosing is that the drugs have a half life of 5-7 days, so it just makes sense, and I think a fair few people who do not like the idea of self injecting are going to be a lot more comfortable doing it once a week rather than more often, especially at the start. And it is a lot easier to remember your dose weekly than every 5 or 6 days.
The reason for splitting doses is to reduce side effects that happen with blood level peaks around 24 hours after a dose, but then are OK after that. If they are bad all week then reducing the dose is the only sensible response. If hunger gets worse 5 or 6 days after a dose you could either just increase the dose if side effects are not an issue or if at maximum dose or you are getting side effects then dose more frequently either every 5 or 6 days or twice a week.
When I started on semaglutide any attempt to get the dose above 0.5mg per week caused nausea for the next day or two, and I was still hungry and the only way to get the dose any higher was to split it into second daily doses so I could get to 0.8mg/week.
The fact that there is not much science on more frequent dosing, I really don't think it matters much, I doubt it changes the amount of weight lost , or anything else, it is really just to help manage side effects or if hunger suppression lasts less than a week.
The reason for splitting doses is to reduce side effects that happen with blood level peaks around 24 hours after a dose, but then are OK after that. If they are bad all week then reducing the dose is the only sensible response. If hunger gets worse 5 or 6 days after a dose you could either just increase the dose if side effects are not an issue or if at maximum dose or you are getting side effects then dose more frequently either every 5 or 6 days or twice a week.
When I started on semaglutide any attempt to get the dose above 0.5mg per week caused nausea for the next day or two, and I was still hungry and the only way to get the dose any higher was to split it into second daily doses so I could get to 0.8mg/week.
The fact that there is not much science on more frequent dosing, I really don't think it matters much, I doubt it changes the amount of weight lost , or anything else, it is really just to help manage side effects or if hunger suppression lasts less than a week.
Peotidethrowaway said:Really? I had no idea.
I’m more interested in analysis of the efficacy when dosed every 7 days vs more frequently. Guess no one is interested in a scientific discussion around these parts. Carry on with vendor discussion I guess. I’ll head over to fight club for more in depth discussion
Minimizing peaks and valleys is going to be more about having a consistent level, theoretically avoiding the side effects of the peak and the feeling of it wearing off in the valley. Functionally, dosing any drug more frequently than its half-life leads to more accumulation unless you adjust the dose to compensate. Efficacy is a tough thing, here, because some people like that peak, and others don't. You could dose it once every 35 days if you wanted to (5 half-lives), and theoretically that would be equivalent in terms of drug exposure time (area under the curve) compared to dosing weekly, or daily. Assuming same total milligram dosing.
lessthanhalf said:
Not singling you out, but in general I see people say that the half life justifies the efficacy of weekly dosing and I don’t understand the logic. I agree they are designed for weekly dosing to improve adherence to dosing schedules which makes FDA approval easier.
Test C has a slightly longer half life and used to be prescribed as an every other week injection, which moved to once a week, to now commonly being prescribed for self administration multiple times a week. The reason for every other week was adherence, no one wants to go to a clinic to get dosed multiple times per week. The results were very sub par with large peaks and long lows, riding a hormonal rollercoaster while calling it therapy. Naturally we have a rhythm with Test (and GLP), but those rhythms are daily (circadian), not weekly.
Like with test, you can have a lower average exposure with a GLP by split dosing… I don’t know that is beneficial in itself (like it is with Test), but it seems that the max dose of a GLP is typically symptom limited.
theoretical_maximum said:
If the drug has first-order elimination, like Reta, Tirz, Sema, Testosterone, etc, that is not accurate.
I suspect that in the end dosing frequency will be guided more by side-effect management than by trying to optimize peaks and valleys. That seems to be where most of these drugs eventually land, but curious if reta ends up proving different.Peotidethrowaway said:
I had not realised there were forums about GLP's when I started on ozempic and had horrible nausea a day after a dose, and just worked out from trial and error and trying to hand graph out drug levels on paper from the half life to try to work out what was going on, and ended up on 2nd daily dosing which was an improvement. A fair percentage of people on grey GLP's end up on some sort of split dosing system.
Not everyone has problematic side effects, or has the effect run out in less than a week, and if you don't I cannot see much advantage in messing with the dosing. And for most people the dose is limited by not wanting to go over the recommended amount rather than side effects, but those doses were chosen for a reason, for most people going above those doses will only cause a marginal improvement in weight loss for a lot of extra side effects, getting well into diminishing returns territory. The 16mg semaglutide study was interesting , a bit more weight loss and a lot more side effects which is what I would expect.
The only one that might have a significantly higher maximum weight loss at higher doses is retatrutide*, but I think its doses would be limited by side effects in a lot of people if higher doses were tried. I have seen people on higher doses of tirzepatide of 20 or 25mg/week but so far I have not seen anyone on more than 12mg of reta, which is interesting. My interpretation of this is tirzepatide has higher GIP agonism and biased GLP-1 agonism, both reducing gastrointestinal adverse effects improving tolerance of higher doses.
* this study tried to create formulas of effectiveness at different doses for the different GLP's
Not everyone has problematic side effects, or has the effect run out in less than a week, and if you don't I cannot see much advantage in messing with the dosing. And for most people the dose is limited by not wanting to go over the recommended amount rather than side effects, but those doses were chosen for a reason, for most people going above those doses will only cause a marginal improvement in weight loss for a lot of extra side effects, getting well into diminishing returns territory. The 16mg semaglutide study was interesting , a bit more weight loss and a lot more side effects which is what I would expect.
The only one that might have a significantly higher maximum weight loss at higher doses is retatrutide*, but I think its doses would be limited by side effects in a lot of people if higher doses were tried. I have seen people on higher doses of tirzepatide of 20 or 25mg/week but so far I have not seen anyone on more than 12mg of reta, which is interesting. My interpretation of this is tirzepatide has higher GIP agonism and biased GLP-1 agonism, both reducing gastrointestinal adverse effects improving tolerance of higher doses.
* this study tried to create formulas of effectiveness at different doses for the different GLP's
Good questionPeotidethrowaway said:
I would like to read the experience from someone that experimented both options.
Visualize peaks and valleys with various intervals and dosage changes:
GLP-1 Plotter - Semaglutide (Ozempic/Wegovy) & Tirzepatide (Mounjaro) Dose Calculator
Plot graphs and calculate levels for GLP-1 Receptor Agonists Semaglutide (Ozempic/Wegovy/Rybelsus) or Tirzepatide (Mounjaro) based on dose & half-life.
glp1plotter.com
[Ignore the sema/tirz blurb ... reta is also selectable.]
And as for the OP question, I can't imagine any reason why peaks & valleys would be beneficial for retatrutide use as a medication to treat the medical problem of metabolic syndrome. That sounds like gymbro nonsense, where the whole world is seen as "cycles" (along with "stacks," "running," etc.). And I see no reason to search for one.
GLP-1 Plotter - Semaglutide (Ozempic/Wegovy) & Tirzepatide (Mounjaro) Dose Calculator
Plot graphs and calculate levels for GLP-1 Receptor Agonists Semaglutide (Ozempic/Wegovy/Rybelsus) or Tirzepatide (Mounjaro) based on dose & half-life.
glp1plotter.com
[Ignore the sema/tirz blurb ... reta is also selectable.]
And as for the OP question, I can't imagine any reason why peaks & valleys would be beneficial for retatrutide use as a medication to treat the medical problem of metabolic syndrome. That sounds like gymbro nonsense, where the whole world is seen as "cycles" (along with "stacks," "running," etc.). And I see no reason to search for one.
I personally like Mon/Thurs or I tend to talk myself into a cheat day over the weekend.
There are some physicians who believe receptor downregulation may be increased with split dosing--which is bad. i.e. the peaks and valleys of GLP-1 in blood serum are actually desirable. This youtube vid by Dr. Kevin Joseph goes into it:
View: https://youtu.be/FjyZSXPrbyk?t=236
View: https://youtu.be/FjyZSXPrbyk?t=236
I'm sorry you're getting such poorly informed responses here. To clear a couple things up:
Weekly was not selected because it was therapeutically optimal. It was selected because it was optimal for patient compliance. Your average person doesn't want to have to plot out their dosing on a calendar. They just want to know "Friday is shot day" and keep it as simple as that. If it turned out that twice a week was a superior schedule it's unclear if pharma would chase after that. If it let them beat the competitor by reporting a higher weight loss percentage in a clinical trial they might do it, but otherwise their priority is to maximize revenue and maximizing compliance is how they do that.
I think a better question to ask might be to ask people who broke "stalls" if they found that changing their dosing approach was part of what they found useful in doing so and what pros and cons people noticed with different approaches.
We can't turn to naturalistic principles to inform us on which might be better, since (if you're not taking these drugs) your GLP-1, GIP, and glucagon levels will naturally vary and fluctuate from hour to hour throughout the day. Pondering whether fluctuating between two different excessively high values every week vs every 3 days is on an entirely different timeline than what our bodies naturally do and neither allows for a "low" level to ever be achieved.
@lessthanhalf brought up an excellent point about side effect avoidance benefits. For example, if you're on a weekly 10mg dose and a certain side effect only kicks in when your total dosage is 18mg or greater than you're in for at least a day of misery every week. Meanwhile, someone taking 5mg twice a week would never experience that side effect.
Another consideration might be in regards to maximum dosing. The clinical trials never pushed the envelope to extra high doses to see if that would be safe or how much more effective doing so would be. As an example, let's say you decided that your own personal tolerance was 20mg maximum dosage (e.g. 10mg weekly dosing). You could stay under that same 20mg maximum dosing on a 5.8mg twice a week schedule (11.6mg weekly total).
Weekly was not selected because it was therapeutically optimal. It was selected because it was optimal for patient compliance. Your average person doesn't want to have to plot out their dosing on a calendar. They just want to know "Friday is shot day" and keep it as simple as that. If it turned out that twice a week was a superior schedule it's unclear if pharma would chase after that. If it let them beat the competitor by reporting a higher weight loss percentage in a clinical trial they might do it, but otherwise their priority is to maximize revenue and maximizing compliance is how they do that.
I think a better question to ask might be to ask people who broke "stalls" if they found that changing their dosing approach was part of what they found useful in doing so and what pros and cons people noticed with different approaches.
We can't turn to naturalistic principles to inform us on which might be better, since (if you're not taking these drugs) your GLP-1, GIP, and glucagon levels will naturally vary and fluctuate from hour to hour throughout the day. Pondering whether fluctuating between two different excessively high values every week vs every 3 days is on an entirely different timeline than what our bodies naturally do and neither allows for a "low" level to ever be achieved.
@lessthanhalf brought up an excellent point about side effect avoidance benefits. For example, if you're on a weekly 10mg dose and a certain side effect only kicks in when your total dosage is 18mg or greater than you're in for at least a day of misery every week. Meanwhile, someone taking 5mg twice a week would never experience that side effect.
Another consideration might be in regards to maximum dosing. The clinical trials never pushed the envelope to extra high doses to see if that would be safe or how much more effective doing so would be. As an example, let's say you decided that your own personal tolerance was 20mg maximum dosage (e.g. 10mg weekly dosing). You could stay under that same 20mg maximum dosing on a 5.8mg twice a week schedule (11.6mg weekly total).
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