丽塔需要经历高峰和低谷吗？

[tubby]

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

Although it sounds like a reasonable argument, these drugs are targeting GLP-1 levels that wouldn't normally be achieved by humans (even at their weekly minimums before the next shot is taken). And that small taste of hunger you're getting is nothing compared to what you would feel if the drug effect could temporarily be eliminated from your body entirely at that point. I'd agree with him that if levels were allowed to vary back to normal that could be desirable, but unless you're spacing out your doses to monthly, that's not really happening.

 

[Lyophilized]

Naturally in our body, what peptides, hormones etc are released every 5 or 7 days?

Maybe in women (estrogen and progesterone) there is a cycle.. But what about the rest, like insulin, glucagon and our natural glp-1?

We have naturally peaks and valleys of almost everything everyday. Correct if I'm wrong

So I think that even if someone wants to inject Reta or anything every day in order to reach the same average amount of someone who injects more every 6 days is not a problem in order to have the same results

Nevertheless I'm always looking for opinions and testimonials from people with their own experiences.

 

[desinr-gal]

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 made my decision based on the GLP1 plotter web page. https://glp1plotter.com/

It will show you the peaks and valleys based on inputs. I highly recommend trying it.

Everything I've read about the official protocal timing has been focused on "patient Compliance". Not patient experience with side effects. Apparently, the fear of needles is a higher deterrent than uncomfortable side effects.

It has been my experience that breaking up doses into lower, more frequent dosing helped me avoid most, if not all, regularly reported side effects. My weightloss was higher than avg trial results at higher doses, as well.

So I stand by my viewpoint that it works better. At least for me. What I have seen on forums is that peoples experiences vary widely!

 

[GeraltRedhammer]

Peaks and valleys are very useful for effective weight loss. Why? Because then it is easier to eat less sometimes and more at other times, which promotes weight loss and muscle building.

It is worth starting with a 24-36 hour fast. If we do not eat anything during this time, we will increase our growth hormone levels several times over (which protects against muscle burning and promotes fat burning). After fasting, we can eat a little and do some strength training. The next day, eat normally and do heavy strength training - this should give better results because we have more growth hormone after fasting, then reduce your calorie intake again and decide on another fast.

With a little experience, we can support ourselves appropriately when we want to fast and let go when we want to exercise. It's a demanding strategy, but it allows you to build muscle while losing weight and slowly but steadily increase your calorie requirements while most people are reducing theirs.

The most important thing is to have a plan and use medication in the most effective way possible.

 

[on2jinm]

I think that there's a hint to be found in the dosage regimen for the new Semaglutide pill. It's once daily, which keeps, more or less, a constant level of the peptide in your system. If peaks and valleys were necessary, you would think they would have set a once weekly schedule with a much higher dose pill. Pills are easy for most people, injections not so much.

 

[CNCCurrency]

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.

Since I started reta I average about 7 bpm higher, I read somewhere that it is to be expected with reta

 

[Nopenada]

I’m on 1mg twice a week and still getting peaks and valleys. I lost a pound early on but now I’m in a stall. Going up to 1.5 once a week was too rough, so I’m keeping things the way they are and tittering up even more slowly is how this will have to go because side effect management has to be a priority over fast weight loss.

In fairness, I have five pounds to lose and I’m a short middle aged woman. So there is a lot of variation from person to person. Definitely not finding the peaks and valleys helpful.

 

[Calm Logic]

The peaks and valleys with weekly dosing didn't stop me from losing weight, but I don't think they are necessary.

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.

Bingo, this is a very long cruise (in bro speak), like those people who retire on a cruise ship. We will not be visiting the ports.

The reset your receptors thing is mostly BS, as far as I can tell. I took a month off tirz (for a break from sides), and that didn't help at all for resuming tirz more effectively.

 

[desinr-gal]

I’m on 1mg twice a week and still getting peaks and valleys. I lost a pound early on but now I’m in a stall. Going up to 1.5 once a week was too rough, so I’m keeping things the way they are and tittering up even more slowly is how this will have to go because side effect management has to be a priority over fast weight loss.

In fairness, I have five pounds to lose and I’m a short middle aged woman. So there is a lot of variation from person to person. Definitely not finding the peaks and valleys helpful.

I add or subtract just .1mg at a time, for couple of weeks..a Higher jump has created a higher jump in BPM for me.

 

[theoretical_maximum]

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

从实际的药代动力学角度来看，这种说法非常值得怀疑。这些药物的药效持续时间非常长。我们通常认为，药物积累在5个半衰期后停止，药效开始消退。但即使经过5个半衰期，体内仍然会有大约3%的药物残留。对于Reta来说，这意味着35天的药效持续时间。考虑到受体饱和和下调，对于半衰期如此之长的药物而言，每周注射一次或每两周注射一次的差异实际上意义不大。

 

[theoretical_maximum]

我认为新药司美格鲁肽的给药方案中蕴含着一些线索。它每天服用一次，这样可以大致保持体内肽的浓度稳定。如果需要药物浓度出现峰值和低谷，那么他们应该会设计一个每周一次、剂量更高的给药方案。对大多数人来说，服用药片很方便，但注射就没那么容易了。

嗯，口服药和注射剂的药代动力学特征截然不同，所以我觉得没必要过度解读。肠道转运时间、生物利用度、首过代谢等等等等。

很大一部分原因在于依从性，这一点其他人也提到过。没人愿意每天注射，也没人会记得每周吃一次药，所以这种给药方案就显得合情合理了。为什么所有GLP-1受体激动剂都要每周注射一次，即使Tirz的半衰期是5天，Sema/Reta是7天？因为每周同一天注射比较方便，每5天或4天注射一次就意味着每周注射日期不同，这样你就需要注意并记录注射时间。依从性就会下降。如果药物服用起来很复杂，人们就不会服用。

 

[lessthanhalf]

I think it is worth being aware that levels of glp drugs and activation of glp receptors by them is much much higher than that of natural glp-1, somewhere around 30-100 times higher, so the dips in level before the next dose are still way higher than normal physiological responses. I would not expect a 15 times normal versus a 30 times normal receptor activation to make a huge difference to the degree of receptor inactivation ( example of difference between peaks and dips in weekly dosing ) , given that the receptors and their regulatory control systems evolved to respond to much lower doses of natural glp-1. My interpretation of this is that the peaks and dips are unlikely to make any substantial difference to tolerance or receptor desensitisation or receptor internalisation, as activation of those receptors is close to maximal even in the dips.

I think there is some degree of tolerance or receptor desensitisation occurring over the first few months after treatment starts, which is why things like slow gastric emptying improve over time and why gastrointestinal side effects often improve after the first 3 to 6 months.

But, there is really no evidence from the studies that glp drugs lose efficacy ( in terms of weight loss which is their purpose ) over time, people on a stable dose the entire time lose weight for about a year then weight stays the same for up to 4 years. If there was long term loss of efficacy people would be regaining weight over that 4 year follow up and they don't.

The main advantage of weekly dosing is it is easy to remember. I tried doing twice a week and kept messing it up because it is nowhere near as easy to remember if it is 3 or 4 days since the last dose. I found every second day easiest, but I was trying to minimise side effects, which were a major problem for me at the time.

I do not think you can answer the question with pharmacodynamics of total doses over time as the system is extremely complicated, with many complex interactions. The only way is to measure effects on weight with different dosing arrangements, with a proper clinical trial and I just cannot see it happening, the drug companies really do not want people getting confused. They want messaging to be clear, simple and the same for everyone as much as possible, although they are now recognising and admitting that some people are better off on smaller doses due to side effects or even in the case of reta weight loss being too rapid. High discontinuation rates in trials with fixed doses make them look worse than they are in real life where doctors can adjust doses depending on effects and side effects. But I doubt very much they want people to be not sure if doses are meant to be once twice or more times a week.

 

[SpaceJumper]

maximize revenue and maximizing compliance is how they do that.

Wondering how maximizing compliance maximizes revenue? May be a little slow on the uptake over here.

Thanks for the perspective.

 

[lusty]

I do every 3 days keeping the most minimal dose I can and still see results, so I have room to titrate up when I get to where I know the hunger as caused me to rebound from prior failed weight loss tries, usually sub 15% bf. I want to get down to 10-12%.

I only take 0.5mg every 3 days but I do feel the day before my next dose the hunger coming back, I had one weird timing issue not 100% sure what it was but I had a miss match the other day from my dose not sure if ice bath slowed down absorbtion or something but I think my dose took longer to absorb subQ so the food noise came back and I had a pint of icecream, after that the next day I was so unwell, partly due to not having dairy, sugar or gluten for a month but my stomach was killing me all the next day.

I would hate to know what would happen with the peaks and valleys if I did a higher dose every 7 days, I am actually thinking of when I up my dose to go from about 1.17mg per week to 2mg per week I will just do every other day at 0.5mg to up the dose.

The only thing I am worried about though, is I am travelling next week for 8 days and don't want to take my stuff with me, as I am visiting family, so I am thinking of doing 1mg or even 1.5mg before I go to last the 8 days, then I get home will do 1mg then I fly for another 5 days, after that I will do EOD of 0.5mg

 

[Nopenada]

The only thing I am worried about though, is I am travelling next week for 8 days and don't want to take my stuff with me, as I am visiting family, so I am thinking of doing 1mg or even 1.5mg before I go to last the 8 days, then I get home will do 1mg then I fly for another 5 days, after that I will do EOD of 0.5mg

Are you sure your body can handle 1.5mg? That felt and acted like full on food poisoning for me. So be sure you won’t spend the whole first day of your trip on the bathroom floor.

 

[AxlBundy]

All I can say is I feel a heck of a lot better without peaks and valleys. I able to fall into a consistent routine when it’s not a rollercoaster each week.

I’m doing Reta every 5 days. I can barely keep track of which day I’m due and I’d call myself an extreme enthusiast. No way John Q Public pulls that off with consistency. As I taper down, I think a Mon-Thurs schedule may be my optimal just dealing with life.

 

[tubby]

Wondering how maximizing compliance maximizes revenue? May be a little slow on the uptake over here.

Thanks for the perspective.

If pharma sells the full 52 weekly doses in a year to each patient then revenue is maximized for that patient. A more complex dosing scheme that causes someone to take too much could be a risk if it led to some people discontinuing treatment (perhaps due to excessive side effects). A more complex dosing scheme that caused someone to accidentally miss doses would be a threat too, since then they'd be selling less than 52 doses a year.

Likewise, even if the med could be more effective under a different dosing scheme (not saying it is, just that maybe it could be), pharma doesn't necessarily care. Unless that additional effectiveness can be used for marketing purposes (which they definitely would care about), it's just not worth risking patient compliance over. As a simple thought problem, would you be more likely to keep taking a med for life if it led to 30% weight loss instead of 25% weight loss? You (as an individual) might be happier with 30% weight loss, but you wouldn't be any more profitable to them that way. Whatever is "good enough" to keep you on their product is what they want to ensure they deliver.

 

[TTRich]

I believe clinical trials, the only true scientific studies, only use 7 day dosing at this point. Maybe I don't know of others that split though. All other discussion is anecdotal, so here's my experience. I've done 6mg once weekly and I've split the dose 3mg, twice weekly. 6mg works way better FOR ME. The split dose seemed to never give me full benefits and definitely ruined the daily poops I get from 6mg once weekly. Of course, someone else will have the opposite experience. Live and learn what works for you

 

[r4000]

The peaks and valleys with weekly dosing didn't stop me from losing weight, but I don't think they are necessary.

Bingo, this is a very long cruise (in bro speak), like those people who retire on a cruise ship. We will not be visiting the ports.

The reset your receptors thing is mostly BS, as far as I can tell. I took a month off tirz (for a break from sides), and that didn't help at all for resuming tirz more effectively.

From what I've read, the knowledgable endocrinologists take folks off of tirz for a full three months for "receptor reset". Four weeks is not enough. It takes 30 to 40 days just for it to be completely eliminated from your system, and then you need a couple months at zero serum levels.

 

[Calm Logic]

From what I've read, the knowledgable endocrinologists take folks off of tirz for a full three months for "receptor reset". Four weeks is not enough. It takes 30 to 40 days just for it to be completely eliminated from your system, and then you need a couple months at zero serum levels.

Not enough for a small subset of endocrinologists, eh? I could understand why, but the theory never made much sense to me in the first place. If the theory was right, I think should have noticed something different with the second go. And how do you explain the dramatic weight gain with the SURMOUNT trial?

At least with the bro scientists, they seem to conflate chemical tolerance (as with caffeine or other stimulants) with metabolic signaling.