Question

[SLZRdad]

I am currently on 10mg of Tirz and I’m noticing the effect is wearing down after about 4 days after injection. Does this mean I should up the dose or would having multiple doses(JW) per week be more effective? I have a goal to lose 60-70 more lbs and am currently 269lbs by the 4th/5th day I’m so hungry. Been on this dose for 1-1.5 months

 

[PepOhio]

Lot's of people do many different things...

• Lower doses multiple times per week
• Higher dose once a week
• Add a small dose of another peptide halfway through week

Tirz has a 5 day half life so many people feel it wearing off around day 5.
FYI...Sema has a 7 day half life but many people find it less effective by itself since it only works on one receptor instead of 2 for Tirz.
Keep in mind the higher the dose the higher the side effects.
How long have you been on 10mg...It takes 4 weeks for the dosage to level out in your system. It still cycles up and down over the week but the highs and lows even out. If you want to see this you can use something like https://glp1plotter.com/ to graph a peptide over more than 4 weeks.

Personally I am currently experimenting with much smaller doses of Tirz on more frequent schedule because I was on 10mg and struggled with some of the side effects when the dose was at it highest point in the cycle each week.

 

[SLZRdad]

Lot's of people do many different things...

• Lower doses multiple times per week
• Higher dose once a week
• Add a small dose of another peptide halfway through week

Tirz has a 5 day half life so many people feel it wearing off around day 5.
FYI...Sema has a 7 day half life but many people find it less effective by itself since it only works on one receptor instead of 2 for Tirz.
Keep in mind the higher the dose the higher the side effects.
How long have you been on 10mg...It takes 4 weeks for the dosage to level out in your system. It is still a cycles up and down over the week but the highs and lows even out. If you want to see this you can use something like https://glp1plotter.com/ to graph a peptide over more than 4 weeks.

Thanks for the response!
I’ve been on this dose for about 1-1.5 months

 

[PepOhio]

Lots of people dose Tirz on a 5 day schedule...you could even lower the individual doses some maybe...do some graphing with your current amounts and then changes and see how it affects your highs and lows.
For example put your current dose in the graph for weeks 1-6 then add a different dose that starts on week 7 through 16 and doses every 5 days or something and see what it looks like

 

[moonpies4misfits]

I am currently on 10mg of Tirz and I’m noticing the effect is wearing down after about 4 days after injection. Does this mean I should up the dose or would having multiple doses(JW) per week be more effective? I have a goal to lose 60-70 more lbs and am currently 269lbs by the 4th/5th day I’m so hungry. Been on this dose for 1-1.5 months

I've only been on Tirz for 2 months but what I started doing was dosing 2.5mg every 5 days, and then when that started to feel less effective, I bumped the dose up by 0.5mg. I initially tried titrating up from 2.5mg to 5mg after 4 weeks but my body really didn't like that. About to finish up month 2 and I'm doing well at 3mg every 5 days so far with minimal side effects.

 

[dionysos]

Two slightly different courses of action have worked for me @SLZRdad.

FIRST, when using 10mg Retatrutide doses began to be less effective at suppressing my appetite I stacked 0.300mg of Cagrilintide mid-week. My appetite disappeared completely, and for longer than 7 days.

SECOND, When the stacked Cagri-Reta blend suppression began to wear off at two weeks after injection, I titrated upward to a 12mg dosage of Retatrutide ONLY - no Cagrilintide. (In other words the Dosing Protocol called out in the series of Lilley research studies.) And that ALSO has eliminated any hunger.

Stacking low-dose Cagrilintide works for me, AND, following the recommended research dosing protocol works for me. I think we are spoiled for choice.

 

[mostlydamp]

I ended up using a halflife calculating spreadsheet for tirzepatide that I found online. With that as my guide I am dosing every 3 days with just the right number of units to keep the dose in my body somewhat stable. So far it has worked! It's been great. As I reach my goal weight I am going to use it to gently walk back the doses until I find maintenance dosage hopefully less frequently.

 

[Bacchus]

I ended up using a halflife calculating spreadsheet for tirzepatide that I found online. With that as my guide I am dosing every 3 days with just the right number of units to keep the dose in my body somewhat stable. So far it has worked! It's been great. As I reach my goal weight I am going to use it to gently walk back the doses until I find maintenance dosage hopefully less frequently.

Half life is a bit more complicated than that, for more straightforward drugs like testosterone, it's often optimal to dose more frequently to maintain stable blood levels.

But tirzepatide isn't really advisable to dose more frequently than every 5-7 days because of it's slow-release formulation and specific pharmacokinetics, it's designed for steady realease over a longer timespan. The half life of 5 days does not refer to the amount injected, but for how long it takes for the concentration of avtive substance in your blood stream to reduce by half.

chatgpt since im lazy:

Key Differences Between Tirzepatide and Testosterone Dosing:​

• Testosterone Enanthate: Adjusting dosing schedules for testosterone works because the goal is to maintain stable hormone levels. Testosterone enanthate has a half-life of around 4-5 days, and dosing every 3 days can help maintain stable levels by reducing fluctuations. Since testosterone doesn’t rely on a slow-release mechanism beyond its basic pharmacokinetics, frequent dosing works without significant issues.
• Tirzepatide: Tirzepatide, however, is a dual GLP-1 and GIP receptor agonist with a slow-release mechanism that’s engineered for once-weekly administration. After injection, tirzepatide is slowly absorbed into your bloodstream over the course of the week. The half-life of 5 days refers to how long it takes for half of the drug already in your bloodstream to be metabolized and cleared, but due to its slow-release formulation, it continues to provide a steady effect over the entire 7-day period(
  
  Diabetes Journals
  )(
  Diabetes Journals
  ).
  

Why Dosing Every 3 Days Doesn't Work:​

1. Drug Accumulation: If you inject tirzepatide every 3 days, the previous dose hasn't fully released and cleared from your system. This leads to overlapping doses, causing drug accumulation in your bloodstream. Instead of the steady levels intended by the weekly dosing, you end up with higher-than-needed concentrations, which can increase the risk of side effects like nausea, vomiting, and gastrointestinal issues without improving efficacy(
   
   Diabetes Journals
   ).
   
   
2. Receptor Saturation: Tirzepatide’s mechanism is different from testosterone. It works by engaging GLP-1 and GIP receptors, which regulate insulin, appetite, and metabolic processes. Dosing more frequently can lead to overstimulation of these receptors, causing more side effects without providing extra benefits. These metabolic pathways need consistent, regulated engagement, and the once-weekly dosing ensures that receptor activation is balanced(
   
   Drugs.com
   )(
   Diabetes Journals
   ).
   
   
3. Designed for Weekly Dosing: The slow-release formulation of tirzepatide is specifically designed for weekly administration to minimize peaks and troughs and allow for controlled, gradual drug absorption. By sticking to the weekly schedule, you keep the drug levels within the therapeutic range. More frequent dosing (e.g., every 3 days) disrupts this balance and can lead to accumulation of the drug beyond safe levels(
   
   Diabetes Journals
   ).
   

Conclusion:​

While it’s possible to adjust testosterone dosing schedules to maintain stable levels, tirzepatide's slow-release mechanism and receptor-based action are designed for a specific dosing interval (once weekly). Dosing every 3 days leads to drug accumulation, overstimulation of receptors, and greater side effects without providing additional benefits.

 

[mostlydamp]

Half life is a bit more complicated than that, for more straightforward drugs like testosterone, it's often optimal to dose more frequently to maintain stable blood levels.

But tirzepatide isn't really advisable to dose more frequently than every 5-7 days because of it's slow-release formulation and specific pharmacokinetics, it's designed for steady realease over a longer timespan. The half life of 5 days does not refer to the amount injected, but for how long it takes for the concentration of avtive substance in your blood stream to reduce by half.

chatgpt since im lazy:

Key Differences Between Tirzepatide and Testosterone Dosing:​

• Testosterone Enanthate: Adjusting dosing schedules for testosterone works because the goal is to maintain stable hormone levels. Testosterone enanthate has a half-life of around 4-5 days, and dosing every 3 days can help maintain stable levels by reducing fluctuations. Since testosterone doesn’t rely on a slow-release mechanism beyond its basic pharmacokinetics, frequent dosing works without significant issues.
• Tirzepatide: Tirzepatide, however, is a dual GLP-1 and GIP receptor agonist with a slow-release mechanism that’s engineered for once-weekly administration. After injection, tirzepatide is slowly absorbed into your bloodstream over the course of the week. The half-life of 5 days refers to how long it takes for half of the drug already in your bloodstream to be metabolized and cleared, but due to its slow-release formulation, it continues to provide a steady effect over the entire 7-day period(
  
  Diabetes Journals
  )(
  Diabetes Journals
  ).

Why Dosing Every 3 Days Doesn't Work:​

1. Drug Accumulation: If you inject tirzepatide every 3 days, the previous dose hasn't fully released and cleared from your system. This leads to overlapping doses, causing drug accumulation in your bloodstream. Instead of the steady levels intended by the weekly dosing, you end up with higher-than-needed concentrations, which can increase the risk of side effects like nausea, vomiting, and gastrointestinal issueswithout improving efficacy(
   Diabetes Journals
   ).
2. 
   
   
3. Receptor Saturation: Tirzepatide’s mechanism is different from testosterone. It works by engaging GLP-1 and GIP receptors, which regulate insulin, appetite, and metabolic processes. Dosing more frequently can lead to overstimulation of these receptors, causing more side effects without providing extra benefits. These metabolic pathways need consistent, regulated engagement, and the once-weekly dosing ensures that receptor activation is balanced(
   
   Drugs.com
   )(
   Diabetes Journals
   ).
   
   
4. Designed for Weekly Dosing: The slow-release formulation of tirzepatide is specifically designed for weekly administration to minimize peaks and troughs and allow for controlled, gradual drug absorption. By sticking to the weekly schedule, you keep the drug levels within the therapeutic range. More frequent dosing (e.g., every 3 days) disrupts this balance and can lead to accumulation of the drug beyond safe levels(
   
   Diabetes Journals
   ).

Conclusion:​

While it’s possible to adjust testosterone dosing schedules to maintain stable levels, tirzepatide's slow-release mechanism and receptor-based action are designed for a specific dosing interval (once weekly). Dosing every 3 days leads to drug accumulation, overstimulation of receptors, and greater side effects without providing additional benefits.

With regard to halflife, I understand that it means half the drug is eliminated at 5 days. That's the purpose of the spreadsheet. By doing smaller doses you will not accumulate too much medication. It may not be clear what I meant by the spreadsheet, so let me explain. It calculates the dosage that would currently be in tour body at that time based on the halflife of 5 days, so you are definitely preventing overdose by lowering the dose you take.

With regard to oversaturation of the receptors, why do you think that taking less than 15mg per week would lead to oversaturation if given more frequently? I haven't seen that in any research papers. I wasn't able to find the text you replied with online. I'm not really convinced that glp1 receptors work that way if the dosing overall is within reason. Granted tirzepatide is different, but the oral version of drugs like these have been around for years and are taken daily. (Edit: by drugs like these I mean receptor agonists)

 

[Bacchus]

With regard to halflife, I understand that it means half the drug is eliminated at 5 days. That's the purpose of the spreadsheet. By doing smaller doses you will not accumulate too much medication. It may not be clear what I meant by the spreadsheet, so let me explain. It calculates the dosage that would currently be in tour body at that time based on the halflife of 5 days, so you are definitely preventing overdose by lowering the dose you take.

With regard to oversaturation of the receptors, why do you think that taking less than 15mg per week would lead to oversaturation if given more frequently? I haven't seen that in any research papers. I wasn't able to find the text you replied with online. I'm not really convinced that glp1 receptors work that way if the dosing overall is within reason. Granted tirzepatide is different, but the oral version of drugs like these have been around for years and are taken daily. (Edit: by drugs like these I mean receptor agonists)

You most likely won't run into any problems. But when injecting every 3 days, you are taking a new injection before the full dose from your last injection has even entered your blood stream.

Peak concentrations occur within 1-2 days after injection, the slow-release design of tirzepatide ensures that drug levels remain steady throughout the entire week. If you inject every 3 days, you would be adding a new dose just as the drug is peaking from the previous one. This doesn’t lead to a stable level but instead creates higher-than-intended peaks, followed by incomplete clearance.

If you adjust the dosage accordingly you shouldn't run any risk of accumulation since small variations doesn't matter all that much with tirz.

Not saying you can't do it, but from my point of view it makes no sense and should theoretically have 0 benefits

 

[mostlydamp]

You most likely won't run into any problems. But when injecting every 3 days, you are taking a new injection before the full dose from your last injection has even entered your blood stream.

Peak concentrations occur within 1-2 days after injection, the slow-release design of tirzepatide ensures that drug levels remain steady throughout the entire week. If you inject every 3 days, you would be adding a new dose just as the drug is peaking from the previous one. This doesn’t lead to a stable level but instead creates higher-than-intended peaks, followed by incomplete clearance.

If you adjust the dosage accordingly you shouldn't run any risk of accumulation since small variations doesn't matter all that much with tirz.

Not saying you can't do it, but from my point of view it makes no sense and should theoretically have 0 benefits

I get what you are saying now with the peak concentration being delayed from injection, but I disagree that it wouldn't have any benefit taking it more frequently. I'm sure we'll both end up agreeing to disagree, but hear me out. Maybe my understanding is wrong but I don't think so.

If I took a dose every single day with a total 7mg per week or took a dose of 7mg every 7 days, why would taking it every 7 days lead to just as stable of a drug level? If you take it every day, the doses will be kicking every day at a small amount leading to a more stable level. If you take it every 7 days, even if the level peaks in 8 to 72 hours it would still start to reduce by a few days after the injection. On day 7 you ae taking your dose and at that time there will be half the previous dose elimintated, and it will take 8 to 72 hours from that point to get peak concentration. With more frequent dosage just because there is delayed onset doesn’t mean there would be no benefit to more stable levels. Take the new oral trials for semaglutide for example, the dosage is daily (though obviously a different route of admin).

 

[Bacchus]

I get what you are saying now with the peak concentration being delayed from injection, but I disagree that it wouldn't have any benefit taking it more frequently. I'm sure we'll both end up agreeing to disagree, but hear me out. Maybe my understanding is wrong but I don't think so.

If I took a dose every single day with a total 7mg per week or took a dose of 7mg every 7 days, why would taking it every 7 days lead to just as stable of a drug level? If you take it every day, the doses will be kicking every day at a small amount leading to a more stable level. If you take it every 7 days, even if the level peaks in 8 to 72 hours it would still start to reduce by a few days after the injection. On day 7 you ae taking your dose and at that time there will be half the previous dose elimintated, and it will take 8 to 72 hours from that point to get peak concentration. With more frequent dosage just because there is delayed onset doesn’t mean there would be no benefit to more stable levels. Take the new oral trials for semaglutide for example, the dosage is daily (though obviously a different route of admin).

I don't mind agreeing to disagree I think the difference probably is negligible anyway.

I'm not trying to say you are wrong per se - And I had the exact same opinion as you have, which is 100% accurate if you are talking about a drug without a designed slow-release (depending on individual differences, which can be significant, but also negligible).

Testosterone would for example be beneficial to take more frequently to maintain stable blood levels.

The issue here is that, if you add more before the full injection is absorbed, there will be a small increase with every single injection.


We both completely agree on how half life works (more or less, if you start digging into it it gets, complicated-ish because of external factors.

Chapter 1 Pharmacokinetics & Pharmacodynamics - Nursing Pharmacology - NCBI Bookshelf

Half Life - StatPearls - NCBI Bookshelf

• Dosing every 3 days (red line) leads to much higher peaks in drug levels due to the frequent injections before the previous dose has fully decayed. Over time, this leads to accumulation, with drug levels increasing above what is expected from the once-weekly dosing.
• Dosing every 7 days (green line) allows for a more steady drug concentration. The drug peaks after the injection and then gradually decreases, but there’s enough time between doses for the drug levels to fall within a safer, effective range without accumulating too much.

 

[PepOhio]

Peak concentrations occur within 1-2 days after injection, the slow-release design of tirzepatide ensures that drug levels remain steady throughout the entire week. If you inject every 3 days, you would be adding a new dose just as the drug is peaking from the previous one. This doesn’t lead to a stable level but instead creates higher-than-intended peaks, followed by incomplete clearance.

I have no idea whether frequent Tirz dosing causes receptor burn out or not. As far as I know there is NO studies currently on this. I believe the main reason for a once weekly injection regimen is because it makes compliance WAY more likely (Most people have no desire to take injections daily if they absolutely don't need too). AND if they can come up with an even slower release version then EVEN better compliance with a once monthly injection.
BUT by no means does a weekly injection cause drug levels to REMAIN steady throughout the entire week! Well unless ALL the graphing plotters are completely wrong.
Here is a perfect example...Dose 10mg first 12 weeks then dose only 1.4 every day instead starting on week 13 through 24. As you can see this completely eliminates the peaks that cause bad side effects for people at higher doses...If I remember correctly at the max 15mg dose/weekly the PEAK is over 22mg.
I had reached a weekly 10mg dose of Tirz and it ALWAYS causes some BAD days every week. I had just started to experiment with daily "micro doses" of 1.2-1.6 to see if it would eliminate the BAD days. Unfortunately since I am having knee surgery in less than 2 weeks I will have to stop Tirz for a little bit before continuing this line of research. I do understand this dose schedule could cause receptor burnout and might require cycling to reset them. Maybe I am missing something...By no means am I an expert on glp-1's.

 

[Bacchus]

I have no idea whether frequent Tirz dosing causes receptor burn out or not. As far as I know there is NO studies currently on this. I believe the main reason for a once weekly injection regimen is because it makes compliance WAY more likely (Most people have no desire to take injections daily if they absolutely don't need too). AND if they can come up with an even slower release version then EVEN better compliance with a once monthly injection.
BUT by no means does a weekly injection cause drug levels to REMAIN steady throughout the entire week! Well unless ALL the graphing plotters are completely wrong.
Here is a perfect example...Dose 10mg first 12 weeks then dose only 1.4 every day instead starting on week 13 through 24. As you can see this completely eliminates the peaks that cause bad side effects for people at higher doses...If I remember correctly at the max 15mg dose/weekly the PEAK is over 22mg.
I had reached a weekly 10mg dose of Tirz and it ALWAYS causes some BAD days every week. I had just started to experiment with daily "micro doses" of 1.2-1.6 to see if it would eliminate the BAD days. Unfortunately since I am having knee surgery in less than 2 weeks I will have to stop Tirz for a little bit before continuing this line of research. I do understand this dose schedule could cause receptor burnout and might require cycling to reset them. Maybe I am missing something...By no means am I an expert on glp-1's.

View attachment 2206

I do not really believe it can cause burnout either, but it would be safer to assume that it can rather than that it can not - since neither is established as a fact.

And yes, compliance is a large part of it. But the drug itself is designed with a slow release mechanism. So it's not just about the half life, but the fact that the absorption into your blood is delayed, and so is the start of the half life.

So if you inject every 3 days, you are (potentially) adding to your injection before the drug has even been fully absorbed into your blood stream

 

[PepOhio]

@Bacchus​

• 
  

I believe your chart is probably showing the EXACT same dose amount for both dosing at 7 days or 3 days. This would definely cause a build up of TIRZ as your chart shows...and it's important for people to understand that.
But from my graphing you reach an equilibrium of highs and lows after roughly 4 weeks of consistant dosing. Also I believe MOST people dosing more frequently are not necessarly doing the "FULL" weekly dose...especially those dosing even more frequently than 5 days/week.
Here is an example with 3mg dose every 3 days for everyone to see.

 

[Bacchus]

@Bacchus​

• 

I believe your chart is probably showing the EXACT same dose amount for both dosing at 7 days or 3 days. This would definely cause a build up of TIRZ as your chart shows...and it's important for people to understand that.
But from my graphing you reach an equilibrium of highs and lows after roughly 4 weeks of consistant dosing. Also I believe MOST people dosing more frequently are not necessarly doing the "FULL" weekly dose...especially those dosing even more frequently than 5 days/week.
Here is an example with 3mg dose every 3 days for everyone to see.

View attachment 2208

that was not the intention of the chart... but it looks like you are right when i look at it again

My main point is simply that the drug isn't designed to be used that way and should in theory work just fine with a e5d or e7d injection.

I'll sit down and do some digging when i have spare time and make sure I'm not being stupid here. I honestly do agree with the logic that as long as you adjust your dosage accordingly, you should have more stable values the more frequently you inject.

But with the peak being 1-2 days, half life 5-7 days and absorption x days. I do believe the most stable solution for most is injecting every 5-7 days instead of trying to find a sweet spot between 1 and 3.

I could be wrong though

 

[mostlydamp]

@Bacchus​

• 

I believe your chart is probably showing the EXACT same dose amount for both dosing at 7 days or 3 days. This would definely cause a build up of TIRZ as your chart shows...and it's important for people to understand that.
But from my graphing you reach an equilibrium of highs and lows after roughly 4 weeks of consistant dosing. Also I believe MOST people dosing more frequently are not necessarly doing the "FULL" weekly dose...especially those dosing even more frequently than 5 days/week.
Here is an example with 3mg dose every 3 days for everyone to see.

View attachment 2208

Yeah exactly, this is the point of my spreadsheet. I want to make sure not to exceed an overall average dose. I would say with regard to the benefit for me, there is much more consistent appetite suppression without having days of 1200 calories and heartburn or nausea. With 2x/wk or Q 3 days, I never have bad effects and only have good ones. I went to every 3 days because it was janky to do twice weekly for me and I had to keep thinking about what dose to take. With 3 days, or 4 days, or 5 days whatever someone would choose they can find what works best without jumping the doses all over the place, and do a 7 day average of medication taken to stay in the right range. Right now for me it's 3mg every 3 days. If the medication builds up then... free tirzepatide! I'm still way under max dose.