Sema/Thriz/Reta choices

[Here2Learn]

Currently I’m on Sema, up to 1.25mg/week and have been losing an average of 1lb/week or less. I started at a medspa, just shifted to Skye and now researching China direct. My inflammation can vary widely so the scale jumps all over the place. Sema has helped with inflammation and I’m looking into running BPC/TB for. 6-8 week protocol to see if it helps more and than a series of Thymosin Alpha 1 after that.

My question is with the lower pricing of China direct Tirz/Reta is more affordable so it has become and option. Sema makes me SO tired and I feel like some weeks it works really well and other weeks not as much. If you were to change what would you choose? I’ve researched all of them pretty extensively so I know the pro/cons but looking for people who have switched and what they liked or don’t like.

 

[Ghoul]

One of my bff’s has great success on Sema with no sides. It is such a roll of the dice as to which one works best for your body. Someday they will know exactly what it is your body is missing to align with the proper med but I think we are a bit away from that still.

It's not too much of a mystery. You either produce too little of the relevant hormone, too few of the receptors, or have a variant of one or the other that doesn't function normally, which in most cases can be determined genetically,

There are environmental exposures that likely cause these as well, but the genetic component regarding sensitivity to these drugs has been largely figured out and can be tested:

Phenomix Sciences :: Double the effectiveness of weight-loss

The MyPhenome™ test, developed with technology exclusively licensed from Mayo Clinic, unlocks your genetic code revealing answers to WHY you struggle with with weight, so you know WHAT to do.

www.phenomixsciences.com

 

[Here2Learn]

It's not too much of a mystery. You either produce too little of the relevant hormone, too few of the receptors, or have a variant of one or the other that doesn't function normally, which in most cases can be determined genetically,

There are environmental exposures that likely cause these as well, but the genetic component regarding sensitivity to these drugs has been largely figured out and can be tested:

Phenomix Sciences :: Double the effectiveness of weight-loss

The MyPhenome™ test, developed with technology exclusively licensed from Mayo Clinic, unlocks your genetic code revealing answers to WHY you struggle with with weight, so you know WHAT to do.

www.phenomixsciences.com

You had shared that before, wish you didn’t need it ordered by a doctor.

 

[Ghoul]

You had shared that before, wish you didn’t need it ordered by a doctor.

If you contact them with the form below and ask for a referral to a telemedicine provider that can order the myphenom test they'll send you a link.

It can be paid for with FSA money, btw.

Contact :: Phenomix Sciences

www.phenomixsciences.com

 

[SubparMarioBro]

First of all, who are you to judge? Not everyone needs to follow your perspective. Personally, I enjoy eating once a day, not because I fear appetite, but because it brings me mental clarity and allows me to savor my meals fully. It’s like foreplay for me. I understand your comment wasn’t directed at me, but please adopt a broader outlook, there’s no one-size-fits-all approach.

I suspect that some of these narratives about appetite suppression need to shift or people are going to hurt themselves.

I was talking to somebody who’d been very successful at losing weight on a GLP-1, they’d lost every pound they could’ve dreamed for. They also highly valued the appetite suppression they experienced on that GLP-1 and they were carefully managing their maintenance dose in order to maintain effective appetite suppression. And they continued to lose weight all the way to the point where they felt they’d lost too much weight and that this had become a health problem for them. But they’re still on a “maintenance dose” for the appetite suppression.

That’s a problem but so far it’s been a bit of a limited problem. Sema and Tirz produce fantastic results but they don’t generally crash people into the underweight category. Folks end up plateauing at a much better weight than where they started but it’s not necessarily a low weight or even an ideal weight, a lot are still overweight which is fine. It’s a massive improvement from where they were. If the rumor mill is correct that they have a significant number of participants in the Reta phase 3 trial who’ve been dose-reduced due to losing too much weight, this is going to become a much bigger problem when you have a drug that can easily push people underweight and it’s being used in self-managed care by people with body dysmorphia issues.

So I think it’s probably important that we develop a healthier perspective of what long-term success with a GLP-1 looks like. Some of the popular narratives are going to end up causing harm.

 

[Nested]

Appetite suppression on 1mg sema was way greater than on 8mg TIRZ

Did you feel nauseous on 1 mg Sema or was it just strong appetite suppression?

 

[Ghoul]

Did you feel nauseous on 1 mg Sema or was it just strong appetite suppression?

I only experienced nausea with Sema if I "ate beyond my appetite", and then it would be a delayed effect, hitting shortly after eating. Once I started limiting eating to the times I'd feel actual physical hunger, stopping immediately once satisfied regardless of how much was left on the plate, it wouldn't happen.

The GIP in Tirz, among other things, acts as an anti-emetic, ie, it has anti-nausea effects on the brain, so it's much less likely with Tirz. To be honest, if weight loss is the primary goal, I think the nausea acts as a good teacher, retraining the user to only eat when actually hungry, vs on a schedule, by habit, or in response to emotion.

 

[Here2Learn]

I suspect that some of these narratives about appetite suppression need to shift or people are going to hurt themselves.

I was talking to somebody who’d been very successful at losing weight on a GLP-1, they’d lost every pound they could’ve dreamed for. They also highly valued the appetite suppression they experienced on that GLP-1 and they were carefully managing their maintenance dose in order to maintain effective appetite suppression. And they continued to lose weight all the way to the point where they felt they’d lost too much weight and that this had become a health problem for them. But they’re still on a “maintenance dose” for the appetite suppression.

That’s a problem but so far it’s been a bit of a limited problem. Sema and Tirz produce fantastic results but they don’t generally crash people into the underweight category. Folks end up plateauing at a much better weight than where they started but it’s not necessarily a low weight or even an ideal weight, a lot are still overweight which is fine. It’s a massive improvement from where they were. If the rumor mill is correct that they have a significant number of participants in the Reta phase 3 trial who’ve been dose-reduced due to losing too much weight, this is going to become a much bigger problem when you have a drug that can easily push people underweight and it’s being used in self-managed care by people with body dysmorphia issues.

So I think it’s probably important that we develop a healthier perspective of what long-term success with a GLP-1 looks like. Some of the popular narratives are going to end up causing harm.

Reading the posts from those in the Reta trials there have been quite a few who have requested to dose down or the site has made dose down as they dropped below their bmi threshold.

 

[Rippidy Dippidy]

Did you feel nauseous on 1 mg Sema or was it just strong appetite suppression?

Slightly nauseous but nothing I worried about. I used it as an additional appetite suppressant. Lol

 

[Nested]

I only experienced nausea with Sema if I "ate beyond my appetite", and then it would be a delayed effect, hitting shortly after eating. Once I started limiting eating to the times I'd feel actual physical hunger, stopping immediately once satisfied regardless of how much was left on the plate, it wouldn't happen.

The GIP in Tirz, among other things, acts as an anti-emetic, ie, it has anti-nausea effects on the brain, so it's much less likely with Tirz. To be honest, if weight loss is the primary goal, I think the nausea acts as a good teacher, retraining the user to only eat when actually hungry, vs on a schedule, by habit, or in response to emotion.

Do you believe there are advantages to taking a single large bolus dose instead of dividing the dosage into two separate doses throughout the week?

 

[Ghoul]

Do you believe there are advantages to taking a single large bolus dose instead of dividing the dosage into two separate doses throughout the week?

Yes. Immunogenicity is significantly increased via more frequent dosing. I realize this is "invisible", since no one is measuring anti-drug antibodies, but we know from other pharma peptides, rHGH, and even other GLP class drugs, immunity can and does develop rendering these compounds less, or entirely ineffective, sometimes permanently,

Couple this with the fact UGL peptides are already "sloppy", both in production and handling by us, the end users, so they're more immunogenic than pharma is already.

What is there to gain from risking a potential lifelong reduction in effectiveness to these crucial drugs with more frequent dosing when the pharma protocols work, as is? Faster weight loss? GLPs aren't fast enough on the weekly dosing schedule?

 

[Rippidy Dippidy]

Do you believe there are advantages to taking a single large bolus dose instead of dividing the dosage into two separate doses throughout the week?

I find also that my appetite slightly creeps back up around day 5 of my last shot. So I do it twice a week

 

[Nested]

You mentioned that you are combining the 1mg Sema with another GLP. Could you clarify whether it’s Tirz or Reta?

 

[ineffectual]

I find also that my appetite slightly creeps back up around day 5 of my last shot. So I do it twice a week

I wish I would have read Ghouls ramblings when I first started. Even a slight chance of glp1's never working for me again is not worth the stacking and other such things people do. I'm currently maintaining the same weight plus or minus a few pounds daily dosing once per week.

My hunger feelings are more than when I was losing. I find myself searching for sweets, not as bad as before. I weight daily. Regardless I still get full when I eat. I spent over 2 decades never actually getting full before. The nights I'm thinking I really messed up sometimes the scale goes down a little.

I say this to make a point try and not be afraid of hunger. It's a challenge. For me every time I feel really hungry the thought here we go again comes up. Still just playing around I'm going to up my dose next time to see what happens.

I would love to go on a bulk, but fear.

 

[Ghoul]

I wish I would have read Ghouls ramblings when I first started. Even a slight chance of glp1's never working for me again is not worth the stacking and other such things people do. I'm currently maintaining the same weight plus or minus a few pounds daily dosing once per week.

My hunger feelings are more than when I was losing. I find myself searching for sweets, not as bad as before. I weight daily. Regardless I still get full when I eat. I spent over 2 decades never actually getting full before. The nights I'm thinking I really messed up sometimes the scale goes down a little.

I say this to make a point try and not be afraid of hunger. It's a challenge. For me every time I feel really hungry the thought here we go again comes up. Still just playing around I'm going to up my dose next time to see what happens.

I would love to go on a bulk, but fear.

You can lower the dose to the point you're able to bulk without worrying about worsening immunogenicity, according to what we know about the dynamics of anti-drug antibodies forming. "Continuous exposure" is much safer in this regard than a complete break.

 

[ineffectual]

You can lower the dose to the point you're able to bulk without worrying about worsening immunogenicity, according to what we know about the dynamics of anti-drug antibodies forming. "Continuous exposure" is much safer in this regard than a complete break.

Oh it's a huge mental issue right now. Like, the thought of gaining after struggling for years of not wanting to be a mass of lard but not being able to stop shoveling everything in sight in my face hole. It was my New Years resolution to slowly lower and bulk but right now mentally I can't. I think I need to show myself I have these new tools. They do work, they will work, If I mess up its now a super easy fix.

I still feel like a larger guy. Looking at my body in pictures, who is that? Inside my head its so different. Looking at my gut and chest while doing planks though is kinda hilarous.

 

[clearheaded]

I wanted to circle back to this. I started taking 500mg of taurine and have been blown away by the energy boost I have gotten. Unfortunately I have had an increase in leg cramps. lol. I was down to one every 4-6 weeks on my electrolyte capsules but when adding taurine I am getting them at least once a week. Also getting them in the leg I never used too. . No clue on this one.

how's ur kidneys? blood sugar? try magnesium. do u drink way too much water? not enough? are you in ketosis?

 

[SubparMarioBro]

Yes. Immunogenicity is significantly increased via more frequent dosing. I realize this is "invisible", since no one is measuring anti-drug antibodies, but we know from other pharma peptides, rHGH, and even other GLP class drugs, immunity can and does develop rendering these compounds less, or entirely ineffective, sometimes permanently,

Couple this with the fact UGL peptides are already "sloppy", both in production and handling by us, the end users, so they're more immunogenic than pharma is already.

What is there to gain from risking a potential lifelong reduction in effectiveness to these crucial drugs with more frequent dosing when the pharma protocols work, as is? Faster weight loss? GLPs aren't fast enough on the weekly dosing schedule?

Something I’ll point out. The first Sema obesity study (phase 2) actually used QD dosing at up to 0.4mg/day for 52 weeks. The report mentions that “no participant developed anti-semaglutide antibodies during the study”.

The bad news for the alternative dosing crowd is that the study reported 13.8% weight loss at 0.4mg/day for 52 weeks, which is a higher dose and less weight loss than found in weekly dosing studies of the same length (Step-5 got 15.6% weight loss at 2.4mg/week for 52 weeks).

https://gwern.net/doc/longevity/glp/semaglutide/2018-oneil.pdf

 

[Ghoul]

Something I’ll point out. The first Sema obesity study (phase 2) actually used QD dosing at up to 0.4mg/day for 52 weeks. The report mentions that “no participant developed anti-semaglutide antibodies during the study”.

The bad news is that the study reported 13.8% weight loss at 0.4mg/day for 52 weeks, which is a higher dose and less weight loss than found in weekly dosing studies of the same length (Step-5 got 15.6% weight loss at 2.4mg/week for 52 weeks). But I haven’t looked closely, that sort of difference could be explained by details of the study design.

https://gwern.net/doc/longevity/glp/semaglutide/2018-oneil.pdf

,

Pharma puts a tremendous effort into avoiding immunogenicity from initial development, to manufacturing, and packaging. Aggregates, for instance, trigger exponentially more antibody formation than an aggregate free pharma formulation.

One of many factors, PH, determines how aggregate formation prone a compound is. Pharma semaglutide contains ph control excipients, and obviously made to very tight specifications. What's the PH of UGL Sema? (it's completely uncontrolled and random).

Here are the immunogenic reactions (antibody formation) the FDA measured in pharmaceutical GLP-1s (on the left) and Compounding pharma, "legal UGL", Sema and Tirz on the right.

DS6 is Exenatide, the pharma GLP with the worst immunogenicity, causing the drug to become ineffective for a significant number of diabetics over time.

Look at how much worse the compounding pharmacy's products are. I'd say, as awful as those are from an immunogenicity perspective, it's almost certain those are still likely better than any UGL.





On another note. the chart on the right shows that filtering can potentially reduce immunogenicity by 80%.

 

[Here2Learn]

how's ur kidneys? blood sugar? try magnesium. do u drink way too much water? not enough? are you in ketosis?

I have this narrowed down to the added magnesium drink and/or electrolyte drink. I already take the electrolyte capsules before bed but am figuring out when I take the added drink for a couple of days that is when I get the leg cramps. An issue of too much of a good thing.

 

[BrunoES]

,

Pharma puts a tremendous effort into avoiding immunogenicity from initial development, to manufacturing, and packaging. Aggregates, for instance, trigger exponentially more antibody formation than an aggregate free pharma formulation.

One of many factors, PH, determines how aggregate formation prone a compound is. Pharma semaglutide contains ph control excipients, and obviously made to very tight specifications. What's the PH of UGL Sema? (it's completely uncontrolled and random).

Here are the immunogenic reactions (antibody formation) the FDA measured in pharmaceutical GLP-1s (on the left) and Compounding pharma, "legal UGL", Sema and Tirz on the right.

DS6 is Exenatide, the pharma GLP with the worst immunogenicity, causing the drug to become ineffective for a significant number of diabetics over time.

Look at how much worse the compounding pharmacy's products are. I'd say, as awful as those are from an immunogenicity perspective, it's almost certain those are still likely better than any UGL.


View attachment 313940


On another note. the chart on the right shows that filtering can potentially reduce immunogenicity by 80%.

Can you share the link?