Modified titration schedule q3d vs trial schedule q7d

[nkresho]

I've been playing with excel a bit today and figured i'd share for the good of the group.

So i have been researching half-life some and comparing the trial dosing schedule against a more frequent schedule (like i'm using).

Here's what i found.

First, i made an excel formula to calculate the 6 day half life over time.

the prior day's saturation multiplied by 0.5 to the power of the number of days over 6

Using this math, on day 6, saturation is half, then on day 12 it's a quarter and so on...



So then i made a schedule showing my dosages each day.

I decided on an every 3 days dosing schedule and loosely following the trial starting dose of 2mg. So week 1 is 1mg day 1, then another 1 3 days later for 2mg in 6 days. So it's not exactly 2mg per week, it's a little more since i am going with 6 days.

here's 45 days under my modified schedule:



then here's the same 45 days under the trial (2mg start) schedule



I added a graph to each to show the peaks and troughs. Obviously, the q3d is smoother. More importantly, the peaks and troughs (far right column of numbers) is much more stable with the more frequent dosing.

Even with the accelerated timeline of 6 days vs 7 days, the saturation numbers are relatively close at the 45 day mark. Trial numbers peak to 6.88 in that last week and trough to 3.24 (difference of 3.64) within the same week. the 6 day schedule peaks at only 5.91 but the closes trough is 3.96 (difference of 1.95)

Just throwing this out there for anybody else who wants to nerd out.

 

[BNLFL]

No offense, but way too much work. I just blast 8mg on Friday.

 

[390120]

just use https://glp1plotter.com/ instead

I did every 6 days for months which worked well, every 3 days i tried for two weeks but felt too nauseous

 

[lessthanhalf]

I am guessing reta? I have personally found that more frequent smaller doses are very effective at managing side effects and allowing higher total weekly doses for a given level of side effects, as in me dose of reta/tirz are both limited by skin sensory symptoms where tiny dose increases from either 4.5mg tirz or 1.4mg reta per 2 days make it worse.

The thing to take into account with any titration schedule is to modify it based on side effects or even useful effects like less hunger , if low grade side effects (like nausea being the most likely to happen at a given dose), it is a pretty good indicator you will get the same effect but worse at a slightly higher dose, so it is usually a good idea to slow down the dose increases if side effects happen, especially if you are using smaller more frequent doses to escalate doses faster than the standard rate.

 

[eidos]

This isn't math, but biochemistry, chemistry, statistical physics (Gibbs energy), and fluid mechanics (laws of diffusion).

You have to take into account the rise to peak concentration, during which Reta begins to take effect, but begins to degrade too (24 to 72 hours). The published half-life is an average with an observed variation of plus or minus about one day (and I’ve mostly read an average around 5.7-5.8 days).

There are three receptors with different affinities, and for some, genetic variations that reduce affinity by a factor of 160.

Reta remains for a long time on albumin, which causes its half-life. This is another reservoir that will result in variations depending on the individual.

What's really going on is much more complicated and can't be reduced to a single number.

You'd better relying on the biological effects you feel. Side effects, hunger, fasting blood sugar, and postprandial blood sugar...

And please learn how to use the button to display two significant figures: your table is unreadable.

 

[nkresho]

I am guessing reta?

yup, reta, i definitely left out a very critical detail, ha.

This isn't math, but biochemistry, chemistry, statistical physics (Gibbs energy), and fluid mechanics (laws of diffusion).

You have to take into account the rise to peak concentration, during which Reta begins to take effect, but begins to degrade too (24 to 72 hours). The published half-life is an average with an observed variation of plus or minus about one day (and I’ve mostly read an average around 5.7-5.8 days).

There are three receptors with different affinities, and for some, genetic variations that reduce affinity by a factor of 160.

Reta remains for a long time on albumin, which causes its half-life. This is another reservoir that will result in variations depending on the individual.

What's really going on is much more complicated and can't be reduced to a single number.

You'd better relying on the biological effects you feel. Side effects, hunger, fasting blood sugar, and postprandial blood sugar...

Great points about the degradation and just the general theory of it. All will be metabolism-specific and highly variable from person to person.

And please learn how to use the button to display two significant figures: your table is unreadable.

The images should be clickable then you can zoom in, if needed. They are for me at least on PC and tablet.

 

[nkresho]

just use https://glp1plotter.com/ instead

I did every 6 days for months which worked well, every 3 days i tried for two weeks but felt too nauseous

This is what i was looking for for like 2 days. Yes, same thing i was looking to accomplish. I never found it so i made my own.

So much easier to tweak and review concentrations too.

This is exactly what i was trying to do:





first 4 weeks ramp up to about 3mg concentration, next 4 peaking at 4, then subsequent 4 weeks peaking at 5. 3 day protocol keeps the valleys only about 1gm less than the peaks.

 

[kj4otu]

I've been wondering something about this. I do get split dosing to manage side effects, but considering our bodies are very cyclical in nature, I wonder if the more cyclical serum levels of once a week dosing might be more functional for glp's. I wonder if the drop in level at the end of the weeks produces a reset effect for the body so there isn't a constant level of "lose lose lose" being sent, but instead there is a rest period at the end of each week before the next dose. I really wish the clinical trials were actually about science and patient care instead of also being about money and getting good numbers for marketing. This info would be a good thing to test scientifically in a trial...

 

[lessthanhalf]

I've been wondering something about this. I do get split dosing to manage side effects, but considering our bodies are very cyclical in nature, I wonder if the more cyclical serum levels of once a week dosing might be more functional for glp's. I wonder if the drop in level at the end of the weeks produces a reset effect for the body so there isn't a constant level of "lose lose lose" being sent, but instead there is a rest period at the end of each week before the next dose. I really wish the clinical trials were actually about science and patient care instead of also being about money and getting good numbers for marketing. This info would be a good thing to test scientifically in a trial...

The levels of naturally occurring GLP-1 and the other peptides are much much lower ( nmol/l ) than those reached by GLP therapy drugs ( micromol/l ) , and only last minutes in the bloodstream. So even at the lowest point between doses, levels are still orders of magnitude higher than the naturally occurring versions. So I do not think there is any significant reset process happening during dips in levels. Not all drugs work this way but there really is minimal evidence of tolerance to glp drugs, except for nausea, vomiting and gastric emptying in the first few months.

Weekly dosing is simple and convenient and fine for most people. Split dosing is mainly to help manage side effects, or it can be used to escalate doses a bit faster with lower risks.