Mixing tesamorelin and hgh

[CraneKraken]

Yeah, I'm on 10mg and that reflux and anhedonia are no joke. Especially the lack of pleasure/enjoyment.
I don't know how you handled 20mg. Must have been brutal. Nice results and good for you. Keep up the good work!

Thanks brotha. Much appreciated. Yeah, I find I can typically use really high doses of most drugs without getting much by way of sides but not with the Tirz. 20mgs was unbearable for me. I keep Tums next to my bed now and take a couple before sleep and more the moment it crops up at night. That seems to help a lot. You're right, the anhedonia is also tough at times. I'm on Adderall IR and the dopamine release I get from it helps keep it at bay, I suspect it helps mitigate the symptoms anyway.

Good luck on your Tirz/fitness journey. I hope you get the results you're looking for. If you find Tirz isn't for you, or you just want to try something new have you thought about jumping on Reta. I imagine I'll be toying with it by the end of the spring. Just to contrast and compare with Tirz.

 

[AlexDavis43]

There is a prolific amount of data showing C-reactive protein drops in people using GLP drugs long before substantial weight loss occurs. This has been observed in both pre-clinical studies and clinical trials.

Anti-inflammatory benefits of semaglutide: State of the art - PMC

Individuals with diabetes often have chronic inflammation and high levels of inflammatory cytokines, leading to insulin resistance and complications. Anti-inflammatory agents are proposed to prevent these issues, including using antidiabetic ...

pmc.ncbi.nlm.nih.gov

Frontiers | Anti-inflammatory effect of semaglutide: updated systematic review and meta-analysis

Background:The anti-inflammatory effect could be one of the mechanisms by which semaglutide reduces cardiovascular risk in patients with type 2 diabetes mell...

www.frontiersin.org

Frontiers | Molecular mechanisms of semaglutide and liraglutide as a therapeutic option for obesity

Obesity, a chronic global health problem, is associated with an increase in various comorbidities, such as cardiovascular disease, type 2 diabetes mellitus, ...

www.frontiersin.org

See bold.

In agreement with Daniel Drucker's opinion on GLP1 efficacy, significant benefits occur very early in an energy deficit. Long before statistically significantly weight loss.

 

[Corduroy]

Interesting study. Am I reading correctly when it also notes that antibodies peak early on (6-22 weeks) and then gradually decline?

You are exactly correct. "At 30 weeks, 36.7% of exenatide twice daily patients were antibody-positive......[which] declined to 16.9% at 3 years." Immune tolerance at work.

"Similarly, 56.8% of exenatide once weekly patients were antibody-positive at 24-30 weeks, declining to 45.4% positive at 52 weeks". They must not have gotten 3 year data, but these numbers are still much higher (in a bad way) than the twice daily group.

Importantly, the antibodies didn't impact efficacy except for in a small subset of each group which had high antibody titers, but even the antibodies in these high titer groups shrank dramatically over time.

So not only did the once weekly exenatide group have more antibodies, but the high titer subgroup was larger and the titers shrank more slowly and less over time compared to the twice daily group.

This argues strongly for immune tolerance as opposed to hyperimmunity from more frequent shots, and since it's the only data available comparing such dosing regimens in a GLP drug, it's the best we've got for now. The story *could* be different for sema/tirz/reta since every molecule is unique, but I don't see a reason to assume that it would be. If anything, it reinforces my position that it's perfectly fine to split doses, and potentially quite beneficial for a number of reasons if one is willing to suffer the inconvenience of two or more injections per week.

 

[Scout23358]

You are exactly correct. "At 30 weeks, 36.7% of exenatide twice daily patients were antibody-positive......[which] declined to 16.9% at 3 years." Immune tolerance at work.

"Similarly, 56.8% of exenatide once weekly patients were antibody-positive at 24-30 weeks, declining to 45.4% positive at 52 weeks". They must not have gotten 3 year data, but these numbers are still much higher (in a bad way) than the twice daily group.

Importantly, the antibodies didn't impact efficacy except for in a small subset of each group which had high antibody titers, but even the antibodies in these high titer groups shrank dramatically over time.

So not only did the once weekly exenatide group have more antibodies, but the high titer subgroup was larger and the titers shrank more slowly and less over time compared to the twice daily group.

This argues strongly for immune tolerance as opposed to hyperimmunity from more frequent shots, and since it's the only data available comparing such dosing regimens in a GLP drug, it's the best we've got for now. The story *could* be different for sema/tirz/reta since every molecule is unique, but I don't see a reason to assume that it would be. If anything, it reinforces my position that it's perfectly fine to split doses, and potentially quite beneficial for a number of reasons if one is willing to suffer the inconvenience of two or more injections per week.

One of my biggest concerns is that for one reason or another I end up getting acclimated to my tirzepatide. I am really interested in seeing whether these results are duplicated in later studies. This medication has been a game changer for me and I’ll happily split doses if need be. Thanks for the study and thoughts!

 

[Ghoul]

You are exactly correct. "At 30 weeks, 36.7% of exenatide twice daily patients were antibody-positive......[which] declined to 16.9% at 3 years." Immune tolerance at work.

"Similarly, 56.8% of exenatide once weekly patients were antibody-positive at 24-30 weeks, declining to 45.4% positive at 52 weeks". They must not have gotten 3 year data, but these numbers are still much higher (in a bad way) than the twice daily group.

Importantly, the antibodies didn't impact efficacy except for in a small subset of each group which had high antibody titers, but even the antibodies in these high titer groups shrank dramatically over time.

So not only did the once weekly exenatide group have more antibodies, but the high titer subgroup was larger and the titers shrank more slowly and less over time compared to the twice daily group.

This argues strongly for immune tolerance as opposed to hyperimmunity from more frequent shots, and since it's the only data available comparing such dosing regimens in a GLP drug, it's the best we've got for now. The story *could* be different for sema/tirz/reta since every molecule is unique, but I don't see a reason to assume that it would be. If anything, it reinforces my position that it's perfectly fine to split doses, and potentially quite beneficial for a number of reasons if one is willing to suffer the inconvenience of two or more injections per week.

You're drawing the wrong conclusion.

Immunogenicty has less to do with the specific peptide than the presence of aggregates, more specifically, the conditions that cause them.

Do you have any idea what the PH is of your reconstituted GLP? That's a primary factor in aggregate formation. That the simplest.
most basic thing established by pharma to keep aggregation, and therefore immunogenicity, to levels below clinical significance. But you have no idea what it is, what it should be, or if there's even a buffer present to control it.

Comparing the end product, as seen in clinical trials, of years, and often tens or hundreds of millions of dollars in development, to some haphazardly produced Chinese knockoff is like suggesting a new BMW proved safe in a crash test, so a goKart bought on Temu must be the same.

Perhaps a pharma produced, low aggregate, peptide delivered in small daily doses doesn't induce additional immunity because it doesn't exceed the threshold necessary to trigger a response from the immune system.

But what happens when it's 20, or 200 or 2000 times more immunogenic as an aggregate loaded peptide can easily be?

Then exposure events matter, since each small dose is enough to get the immune system to respond.

 

[Corduroy]

You're drawing the wrong conclusion.

Immunogenicty has less to do with the specific peptide than the presence of aggregates, more specifically, the conditions that cause them.

Do you have any idea what the PH is of your reconstituted GLP? That's a primary factor in aggregate formation. That the simplest.
most basic thing established by pharma to keep aggregation, and therefore immunogenicity, to levels below clinical significance. But you have no idea what it is, what it should be, or if there's even a buffer present to control it.

Comparing the end product, as seen in clinical trials, of years, and often tens or hundreds of millions of dollars in development, to some haphazardly produced Chinese knockoff is like suggesting a new BMW proved safe in a crash test, so a goKart bought on Temu must be the same.

Perhaps a pharma produced, low aggregate, peptide delivered in small daily doses doesn't induce additional immunity because it doesn't exceed the threshold necessary to trigger a response from the immune system.

But what happens when it's 20, or 200 or 2000 times more immunogenic as an aggregate loaded peptide can easily be?

Then exposure events matter, since each small dose is enough to get the immune system to respond.

I never said anything about Chinese knock-offs, but now that you mention it, do you have anything other than speculation to back up the assumption/assertion that there are significant amounts of peptide aggregates in such products, especially if they are sufficiently diluted and filtered?

It sounds like you are jumping to multiple conclusions, for instance that 1) significant aggregates are being formed in non-branded GLP meds 2) such aggregates cause immunogenicity 3) antibodies formed are the rare kind that actually neutralize the drug, which wouldn't even make sense since the antibodies formed are to the aggregate(s) not the original peptide, and 4) that such antibodies occur with greater frequency with increasing injection frequency rather than the immunotolerance effect we see in the exenatide study.

 

[Letits now]

Peptide test answers this question here

Syringe Filter Impact Study — Peptide Test

www.peptidetest.com

Loss is 5-7 units for a 4mm and 29 units for a 13mm. I use a 4mm filter for peptides because of this.

Damn. Link doesn’t work. Do you have this test?

 

[keenpen]

Damn. Link doesn’t work. Do you have this test?

Thank goodness for archive.org. Give this a try.

Syringe Filter Impact Study — Peptide Test

web.archive.org

Filter Size Matters: The study found that using a 4mm syringe filter results in significantly less volumetric loss compared to a 13mm filter. Specifically, the 4mm filter loses about 5-7 units, while the 13mm filter loses approximately 29 units when filtering a reconstituted peptide solution.

 

[Middus]

Thank goodness for archive.org. Give this a try.

Syringe Filter Impact Study — Peptide Test

web.archive.org

Filter Size Matters: The study found that using a 4mm syringe filter results in significantly less volumetric loss compared to a 13mm filter. Specifically, the 4mm filter loses about 5-7 units, while the 13mm filter loses approximately 29 units when filtering a reconstituted peptide solution.

Just flush with air! Fro cost benefit angle 4mm filter is avoidable stress

 

[keenpen]

Just flush with air! Fro cost benefit angle 4mm filter is avoidable stress

Air purging is addressed in the linked article

2. Air Purge Recovery: For the 4mm filter, performing air purges can help recover some of the lost volume, on average, around 2.2 units of the 7.3 units lost can be recovered through this method, reducing the overall loss. Air purging was not effective on 13mm filter.

At a cost of $1.50, I hope the filter doesn't cause too much additional stress. I love the 4mm filters.

 

[Ghoul]

Air purging isn't really that great in my experience. A lot of bubbles and foam, which you don't want. Better to run the equivalent amount of BAC to the holdup volume through the filter (or in the case of the 4mm, don't bother).

 

[Middus]

Air purging is addressed in the linked article

2. Air Purge Recovery: For the 4mm filter, performing air purges can help recover some of the lost volume, on average, around 2.2 units of the 7.3 units lost can be recovered through this method, reducing the overall loss. Air purging was not effective on 13mm filter.

At a cost of $1.50, I hope the filter doesn't cause too much additional stress. I love the 4mm filters.

Do it yourself.. . We have several anecdotes floating online, from people that performed experiments and posted their results. Just saying.

 

[Kaiserpr]

Interesting info