Pharma Trizepetide Vs Generic

[fw190jd]

Greetings ,

I just finished 2 months of pharma Tirz, fist month not much action at 2.5mg, second month things started popping a little a 5mg, some minor side effects , but we perservered. The price increases with dosage increases with my provider, so I wanted to try a more cost effective approach, I purchased some from my peptide supplier with a Jano report and went up to my next level of 7.5mg, been a week , I would say the food noise is gone, the weight has stopped coming off , I was starting to average 1.5 pounds a week, now I'm heading in the other direction, 2 pounds in a couple of days water weight. I have a tendency to under hydrate.
I always overthink this shit and try to hard, any thoughts ? suck it up and go back to the pharma ?
Looking forward to sme great thoughts as usual, thanks in advance for your help.

 

[Ghoul]

It takes 2 weekly doses to feel the majority of the effects of a new dose, and 4 to reach the maximum blood serum concentration.

However, as someone who's gone back and forth between pharma and multiple vendor's UGL Tirz, UGL is not as potent as pharma at the same dose, in my experience.

I've found UGL to require about one titration level higher to have roughly the equivalent effect, or 20-25% more.

Reconstitute in a way to ensure the volume of each injection is .5ml or more. If not possible get as close to .5ml as you can.

Use Hospira (pharma BAC). UGL BAC and the stuff on Amazon are not reliable which can impact efficacy.

Finally consider filtering. Despite the reliance on so called "purity" tests, UGL peptides are no where near as tightly controlled for impurities and stability. The unknown types and quantities of trash can build a kind of immunity to the drug (and worse) over time. Filtering will help minimize that risk,

 

[fw190jd]

Thank you Goul

It takes 2 weekly doses to feel the majority of the effects of a new dose, and 4 to reach the maximum blood serum concentration.

However, as someone who's gone back and forth between pharma and multiple vendor's UGL Tirz, UGL is not as potent as pharma at the same dose, in my experience.

I've found UGL to require about one titration level higher to have roughly the equivalent effect, or 20-25% more.

Reconstitute in a way to ensure the volume of each injection is .5ml or more. If not possible get as close to .5ml as you can.

Use Hospira (pharma BAC). UGL BAC and the stuff on Amazon are not reliable which can impact efficacy.

Finally consider filtering. Despite the reliance on so called "purity" tests, UGL peptides are no where near as tightly controlled for impurities and stability. The unknown types and quantities of trash can build a kind of immunity to the drug (and worse) over time. Filtering will help minimize that risk,

Thank you Mr Goul,
I always appreciate you as a new member jumping in and helping us newbies understand the ropes I do have a question. In your opening answer you said it takes two weekly doses to feel the majority of the facts so I'm doing a once a week dose of 7.5 mg am I misunderstanding your statement that I should be doing that twice a week? Sorry if I'm sounding stupid here I'm just trying to get it right.

 

[Ghoul]

Thank you Goul

Thank you Mr Goul,
I always appreciate you as a new member jumping in and helping us newbies understand the ropes I do have a question. In your opening answer you said it takes two weekly doses to feel the majority of the facts so I'm doing a once a week dose of 7.5 mg am I misunderstanding your statement that I should be doing that twice a week? Sorry if I'm sounding stupid here I'm just trying to get it right.

Because of the pharmacokinetics of Tirz, it takes about 4 weeks of once a week injections at the same dose to reach the maximum average blood level of a given dose,

So when starting a new dose, if someone is feeling effects a few days after administration, but they're not as strong as desired, it's best not to increase the dose the following week, since you can expect effects to get stronger after the 2nd shot because average blood levels of the drug will rise, even though the 2nd shot is the same dose, This happens to a lesser degree after the 3rd, and will plateau after the 4th.

Some people get inpatient, raise the dose the week following the first, and end up with unpleasant side effects because it's too strong,

If effects are still too weak a few days after the 2nd weekly shot of a given dose, it's ok to titrate up on the next shot.

For reasons I won't bore you with, imo it's best practice to stick to once a week shots. There are unappreciated downsides and potential risks to increasing the frequency of injections, with daily micro-dosing the worst.

A lot of long term users tweak their schedules to time the lower appetite suppression just before the next shot to fall on days they generally go out or want to enjoy a larger meal than they'd usually have.

 

[Sera]

It takes 2 weekly doses to feel the majority of the effects of a new dose, and 4 to reach the maximum blood serum concentration.

However, as someone who's gone back and forth between pharma and multiple vendor's UGL Tirz, UGL is not as potent as pharma at the same dose, in my experience.

I've found UGL to require about one titration level higher to have roughly the equivalent effect, or 20-25% more.

Reconstitute in a way to ensure the volume of each injection is .5ml or more. If not possible get as close to .5ml as you can.

Use Hospira (pharma BAC). UGL BAC and the stuff on Amazon are not reliable which can impact efficacy.

Finally consider filtering. Despite the reliance on so called "purity" tests, UGL peptides are no where near as tightly controlled for impurities and stability. The unknown types and quantities of trash can build a kind of immunity to the drug (and worse) over time. Filtering will help minimize that risk,

https://diabetesjournals.org/diabetes/article/71/Supplement_1/742-P/145872/742-P-Antidrug-Antibodies-Do-Not-Impact

Not sure if you’ve seen this,

7% of participants already had ADA before starting Tirz.

Meaning some of us already had antibodies to native GIP and GLP-1 even without use of sema or tirz etc.

 

[Ghoul]

https://diabetesjournals.org/diabetes/article/71/Supplement_1/742-P/145872/742-P-Antidrug-Antibodies-Do-Not-Impact

Not sure if you’ve seen this,

7% of participants already had ADA before starting Tirz.

Meaning some of us already had antibodies to native GIP and GLP-1 even without use of sema or tirz etc.

The Tirz Surpass trials these results came from didn't exclude diabetics with previous exposure to GLP drugs.

 

[Sera]

The Tirz Surpass trials these results came from didn't exclude diabetics with previous exposure to GLP drugs.

So it’s hard to say for sure where those ADA came from in that case. In any case the percentage of cross-reacting TE-ADA is very low, and there’s no reason to believe UGL tirz would be any worse in this regard. Although filtering to hopefully reduce absolute immunogenicity still seems like best practice.

 

[Ghoul]

So it’s hard to say for sure where those ADA came from in that case. In any case the percentage of cross-reacting TE-ADA is very low, and there’s no reason to believe UGL tirz would be any worse in this regard. Although filtering to hopefully reduce absolute immunogenicity still seems like best practice.

There is no basis to make that extrapolation to UGL Tirz. To the contrary, it shows that neutralizing antibodies ARE created, even by pharma Tirz, making the likelihood the haphazardly produced, packaged, stored, reconstituted, and administered UGL product is far, far worse.

To recap, what Eli Lily's data shows is;

Using Eli Lily's carefully produced Tirz, in Eli Lily's formulation, in packaging engineered to not interact with the drug, administered using Eli Lily's protocol, anti-drug neutralizing antibodies didn't rise to the level of clinical significance.

It did not show that:

Using a random process to manufacture Tirz, with uncharacterized impurities, no external quality control, without ensuring sterility, no immunogenicity study, in cheap (likely contaminated) vials, lyophilized using whatever method is expedient, stored and shipped without temperature controls, formulated with random (or no) excipients, reconstituted to some random PH, at some random dilution, and in many cases injected more frequently at random doses, results in anti-drug neutralizing antibodies below the level of clinical significance.

 

[Ghoul]

It may not be appreciated that for years prior to a human trial, in a process that's kept hidden from public view since it constitutes trade secrets, the specific manufacturing process is tweaked by extensive trial and error, and "in silico" computer simulations to identify every potential immunogenic contaminant that the process could produce. then engineer the most immunogenic contaminants out of the process before seeking FDA approval. I've read 70% of protein drugs in development never get passed this stage since they can't reduce immunogenicity to an acceptable level.

This process extends to storage and the packaging as well,

When the application is submitted to the FDA, the immunogenicity has been wrung out of the product through years of effort, and only then are human trials permitted.

If any step of the manufacturing process changes, or even something as simple as the material used in the containers it's stored in, they must demonstrate to the FDAs satisfaction that no new contaminants that will impact immunogenicity are developed as a result of the change.

UGL does none of this, Which means antibodies could easily be tens, or even thousands of times higher than the pharma product.

The FDA found this in compounded Tirz
and Sema compared to pharma GLP drugs, with one being 2000x more immunogenic than pharma formulations using the standard human cell in vitro test. At those levels, neither of those drugs would have been approved to move forward to human trials.




The fact is no one has any idea what level of antibodies are being induced by UGL peptides, what their impact is, or will be in the long term.

As you can see, from the chart on the right, filtering caused a dramatic reduction in the immune reaction, 80% in one case, so it's a bit of cheap insurance to reduce risk and potentially improve effectiveness.

 

[Sera]

There is no basis to make that extrapolation to UGL Tirz. To the contrary, it shows that neutralizing antibodies ARE created, even by pharma Tirz, making the likelihood the haphazardly produced, packaged, stored, reconstituted, and administered UGL product is far, far worse.

To recap, what Eli Lily's data shows is;

Using Eli Lily's carefully produced Tirz, in Eli Lily's formulation, in packaging engineered to not interact with the drug, administered using Eli Lily's protocol, anti-drug neutralizing antibodies didn't rise to the level of clinical significance.

It did not show that:

Using a random process to manufacture Tirz, with uncharacterized impurities, no external quality control, without ensuring sterility, no immunogenicity study, in cheap (likely contaminated) vials, lyophilized using whatever method is expedient, stored and shipped without temperature controls, formulated with random (or no) excipients, reconstituted to some random PH, at some random dilution, and in many cases injected more frequently at random doses, results in anti-drug neutralizing antibodies below the level of clinical significance.

I was specifically referring to cross reacting ADA to native GIP/GLP-1. Yes I agree that general immunogenicity will be far worse in UGL tirzepatide.

Although it can probably be ameliorated somewhat with 0.22 filtration and we could even go to 0.05 filtration if we wanted. You’ve already made the point that these large aggregates and particulate matter having an adjuvant effect is probably the worst of it so removing that will help to close the gap (at least somewhat) between pharma and ugl tirz

Also there are discord groups where jano and other labs discuss some of the excipients actually in this stuff, not sure if you are in any of those you may find it interesting.

Also the manufacturing process is basically copied by the peptide manufacturers in China from Lilly’s patent was my understanding. I doubt that this aspect introduces much in the way of unique immune responses. There are going to be monomeric contaminants and impurities but to what extent are they going to aggravate the immune system? Probably not much. The novel epitopes presented by aggregates are going to be 99% of it, just from first principles thinking about how the immune system actually works.

 

[Sera]

The fact is no one has any idea what level of antibodies are being induced by UGL peptides, what their impact is, or will be in the long term.

Certainly correct, I intend to limit my use of UGL peptides due to this and will be switching as soon as affordable pharma tirz becomes available.

I’m just trying to steelman the opposite case in order to justify even using it at all though!

I certainly don’t understand the intricacies of the immune system anywhere near enough at this point, but will be doing further reading.