Tirzepatide max dosage

[anon55]

Hello mesoRx !
I'm currently on tirzepatide 20mg once a week and no longer feel it. I can eat and think about food, even do cheat meals almost like I used to do. Weight is not going back. But I hate the food noise, my diet is becoming harder to maintain.
Should I increase the dose to 25 mg weekly? To be honest I kinda want to try if needed up to 30mg weekly.
What's your thoughts? Is there really risks? More than those that we know? Have someone tried those huge dosages?

Thanks

 

[Ghoul]

Do you if tirzepatide effecf on receptors is linear or more like telmisartan or even like a statin?
Most of the benefits come from a low dose and after 15mg there no much differences like between 20 and 40 of rosuvastatin?

GLP and GIP are hormones.

They're not diet pills.

These drugs supplement what you already have.

The impact they have depends on your preexisting endogenous level, and the sensitivity your particular biology has to them, largely dependent on receptor density.

The more GLP in your system, the lower your homeostasis weight "setting" goes,

Once you start feeling the effects of appetite suppression, at a given dose, the lower your weight goes the weaker those effects become, As weight rises, at the same dose, appetite suppression returns as you're pushed back down toward the homeostasis weight.

The "maintenance" dose is where you are at desired weight, but feel no effects from the drug. To lose more, you have to push the homeostasis level down further, by increasing the dose.

I think a large portion of the widespread mental blockage to this simple concept is: "What do you mean appetite (and therefore weight) is primarily regulated by hormones that an individual may be deficient in or insensitive to, like insulin is to diabetes? Everyone knows weight is primarily determined by willpower or the lack thereof.".

 

[anon55]

GLP and GIP are hormones.

They're not diet pills.

These drugs supplement what you already have.

The impact they have depends on your preexisting endogenous level, and the sensitivity your particular biology has to them, largely dependent on receptor density.

The more GLP in your system, the lower your homeostasis weight "setting" goes,

Once you start feeling the effects of appetite suppression, at a given dose, the lower your weight goes the weaker those effects become, As weight rises, at the same dose, appetite suppression returns as you're pushed back down toward the homeostasis weight.

The "maintenance" dose is where you are at desired weight, but feel no effects from the drug. To lose more, you have to push the homeostasis level down further, by increasing the dose.

I think a large portion of the widespread mental blockage to this simple concept is: "What do you mean appetite (and therefore weight) is primarily regulated by hormones that an individual may be deficient in or insensitive to, like insulin is to diabetes? Everyone knows weight is primarily determined by willpower or the lack thereof.".

My logic wich might be false was at a point all receptors would be agonized and then no more effect, like a angiotensin receptor blocker. At 80mg all receptors are blocked and a gram of telmisartan will not lower BP further.

 

[Ghoul]

My logic wich might be false was at a point all receptors would be agonized and then no more effect, like a angiotensin receptor blocker. At 80mg all receptors are blocked and a gram of telmisartan will not lower BP further.

There is a limit, as demonstrated by the Sema 7.2mg trials. However, at pharma protocol doses, that's almost never reached. In other words, going from 1.7 to 2.4 Sema almost always results in more weight loss as does going from 12.5 to 15 of Tirz.

The largest variability seems to be the dose at which appetite suppression begins, after which, response is fairly linear with dose increases until, presumably as demonstrated with the Sema 7.2 trials, there's nothing left to agonize.

What you don't see with the 3 and 4 year extended trials is weight regain. Once a maintenance dose is reached, weight remains stable for years, demonstrating there's no clinically significant "tolerance" that develops.

On the other hand, if every dose is loaded with contaminants, and antibodies increase faster than they dissipate, I would expect a gradual decrease in effectiveness over time. This happened to a small proportion of diabetic exenatide users. Despite being pharma, some individuals were prone to developing antibodies, and after a long period of use, glucose control was gradually lost since their immune systems were clearing exenatide faster and faster over time.

Antibodies are only measured in clinical trials, so there's no way to know how much this is happening among UGL users, but we do get a lot of anecdotes about a "loss of effectiveness" from "tolerance" that isn't reflected in those using pharma.

 

[chmuse]

There is a limit, as demonstrated by the Sema 7.2mg trials. However, at pharma protocol doses, that's almost never reached. In other words, going from 1.7 to 2.4 Sema almost always results in more weight loss as does going from 12.5 to 15 of Tirz.

The largest variability seems to be the dose at which appetite suppression begins, after which, response is fairly linear with dose increases until, presumably as demonstrated with the Sema 7.2 trials, there's nothing left to agonize.

What you don't see with the 3 and 4 year extended trials is weight regain. Once a maintenance dose is reached, weight remains stable for years, demonstrating there's no clinically significant "tolerance" that develops.

On the other hand, if every dose is loaded with contaminants, and antibodies increase faster than they dissipate, I would expect a gradual decrease in effectiveness over time. This happened to a small proportion of diabetic exenatide users. Despite being pharma, some individuals were prone to developing antibodies, and after a long period of use, glucose control was gradually lost since their immune systems were clearing exenatide faster and faster over time.

Antibodies are only measured in clinical trials, so there's no way to know how much this is happening among UGL users, but we do get a lot of anecdotes about a "loss of effectiveness" from "tolerance" that isn't reflected in those using pharma.

Does that imply that a lower dosage working means there's a bigger issue with your receptors and/or hormone levels? Do you think it would also mean if you get the effects at a lower dose, there's a larger potential weight loss?

 

[Ghoul]

Does that imply that a lower dosage working means there's a bigger issue with your receptors and/or hormone levels? Do you think it would also mean if you get the effects at a lower dose, there's a larger potential weight loss?

There's really not enough data to figure out exactly what it means, since there's almost no good data on "metabolically healthy" people to use as a baseline, And, unlike testosterone or estrogen, the short lived nature of naturally produced incretin hormones like GLP makes it extremely difficult to measure their levels, As far as I'm aware, the only way to determine someone's receptor density is via tissue biopsies, so the closest we have are genetic tests that characterize GLP production and sensitivity,

Genetic Test Can Predict Response to Semaglutide

With an assist from machine learning, investigators find a genetic test that can identify obesity phenotypes and predict who will benefit most from semaglutide for weight loss.

www.medscape.com

Observationally though, the people with the strongest appetite suppression response to low doses seem to lose the most ultimately, often not making it anywhere near the max dose before hitting goal weight.

Both Novo and Eli reduced the minimum "maintenance" dose levels as this became apparent. Prior to the adjustment, for instance, if you couldn't make it to 2.4mg Sema within 6 months the guidance told doctors to stop treatment. Then 1.7 became an option. Now it seems to be "whatever" is acceptable because there's so much variability in response,

I suspect sensitivity to low doses simply means the gap between the GLP you produce and what's needed to maintain a healthy weight was small, and when you have no response, that gap is just larger requiring a bigger dose to make up the difference. For a "metabolically healthy" person who doesn't experience appetite suppression at low doses, perhaps they have low sensitivity, but naturally produce enough to overcome that, so that small exogenous doses don't make much of a difference in their particular balance of production to receptors.

There are so many complicating factors that can easily vary from person to person.

A lot of GLP-1's production is determined by the physical stretching of intestinal tissue. Intestine diameter can be as different from person to person as the size of one's nose . (increasing that pressure is one of the main reasons bariatric surgery induces weight loss and improves diabetes, by raising intestinal pressure and increasing natural GLP production).

Taking that a step further, as our foods have become more and more calorie dense, we lack the bulk of low calorie foods that used to stretch the intestines, release GLP, and induce satiety to lower appetites, throwing the whole system out of balance. That's why high fiber diets are associated with lower rates of obesity,

 

[chmuse]

There's really not enough data to figure out exactly what it means, since there's almost no good data on "metabolically healthy" people to use as a baseline, And, unlike testosterone or estrogen, the short lived nature of naturally produced incretin hormones like GLP makes it extremely difficult to measure their levels, As far as I'm aware, the only way to determine someone's receptor density is via tissue biopsies, so the closest we have are genetic tests that characterize GLP production and sensitivity,

Genetic Test Can Predict Response to Semaglutide

With an assist from machine learning, investigators find a genetic test that can identify obesity phenotypes and predict who will benefit most from semaglutide for weight loss.

www.medscape.com

Observationally though, the people with the strongest appetite suppression response to low doses seem to lose the most ultimately, often not making it anywhere near the max dose before hitting goal weight.

Both Novo and Eli reduced the minimum "maintenance" dose levels as this became apparent. Prior to the adjustment, for instance, if you couldn't make it to 2.4mg Sema within 6 months the guidance told doctors to stop treatment. Then 1.7 became an option. Now it seems to be "whatever" is acceptable because there's so much variability in response,

I suspect sensitivity to low doses simply means the gap between the GLP you produce and what's needed to maintain a healthy weight was small, and when you have no response, that gap is just larger requiring a bigger dose to make up the difference. For a "metabolically healthy" person who doesn't experience appetite suppression at low doses, perhaps they have low sensitivity, but naturally produce enough to overcome that, so that small exogenous doses don't make much of a difference in their particular balance of production to receptors.

There are so many complicating factors that can easily vary from person to person.

A lot of GLP-1's production is determined by the physical stretching of intestinal tissue. Intestine diameter can be as different from person to person as the size of one's nose . (increasing that pressure is one of the main reasons bariatric surgery induces weight loss and improves diabetes, by raising intestinal pressure and increasing natural GLP production).

Taking that a step further, as our foods have become more and more calorie dense, we lack the bulk of low calorie foods that used to stretch the intestines, release GLP, and induce satiety to lower appetites, throwing the whole system out of balance. That's why high fiber diets are associated with lower rates of obesity,

Thanks, that gives me a new angle to research how some medications work. Appreciated!

 

[Alex2000]

What is the reason why people regain weight after stopping Tirz? Is it only because they go back to eating the same way as before?

 

[Ghoul]

What is the reason why people regain weight after stopping Tirz? Is it only because they go back to eating the same way as before?

Because the body's energy regulation system, which has evolved multiple potent physical and psychological mechanisms to influence behavior, goes back to its previous state and weight returns to baseline. Conscious willpower can override it, with all consuming, continuous effort to resist, that in almost all cases eventually fails.

 

[AlexDavis43]

What is the reason why people regain weight after stopping Tirz? Is it only because they go back to eating the same way as before?

On GLP1s, they do everything the same but eat less of the same diet. When they go off, still back to the same diet (just more of it, so weight regain).

It's possible to maintain the weight loss if diet/lifestyle is changed during treatment. This time should be used for that. Some doctors are already doing this (educating patients on diet, resistance training, etc.).

GLP1s don't have to be forever drugs.

 

[Ghoul]

On GLP1s, they do everything the same but eat less of the same diet. When they go off, still back to the same diet (just more of it, so weight regain).

It's possible to maintain the weight loss if diet/lifestyle is changed during treatment. This time should be used for that. Some doctors are already doing this (educating patients on diet, resistance training, etc.).

GLP1s don't have to be forever drugs.

Like insulin for type 2 diabetics, and testosterone for hypogonadal men, it's possible to come off of those exogenous hormones via lifestyle changes.

 

[Rippidy Dippidy]

Hello mesoRx !
I'm currently on tirzepatide 20mg once a week and no longer feel it. I can eat and think about food, even do cheat meals almost like I used to do. Weight is not going back. But I hate the food noise, my diet is becoming harder to maintain.
Should I increase the dose to 25 mg weekly? To be honest I kinda want to try if needed up to 30mg weekly.
What's your thoughts? Is there really risks? More than those that we know? Have someone tried those huge dosages?

Thanks

I’d suggest hoping off for 2-3 weeks and trying Sema if appetite is your “issue”
I feel 1mg Sema/taking twice a week 0.5/0.5
More than I feel 10mg Tirz taken twice a week 5/5.
On 10mg Tirz I can eat 1500 cals and not feel full. For me Tirz is no where near as good as Sema.
But then again I really only care about minimizing my appetite

 

[280671]

Hello mesoRx !
I'm currently on tirzepatide 20mg once a week and no longer feel it. I can eat and think about food, even do cheat meals almost like I used to do. Weight is not going back. But I hate the food noise, my diet is becoming harder to maintain.
Should I increase the dose to 25 mg weekly? To be honest I kinda want to try if needed up to 30mg weekly.
What's your thoughts? Is there really risks? More than those that we know? Have someone tried those huge dosages?

Thanks

I started to add metformin 500mg tablet daily alongside my 15mg tirz and works great , gives a definite boost if you have hit a wall

 

[explodingHeart]

That's good. Really no downside to over diluting other than over 1 ml can get uncomfortable.

The normal course of events is, you hit goal weight at a certain dose and stay there indefinitely, no noticeable effects or sides, just "normal" feeling. But of course not everyone gets to goal by 15mg. Sliding back would be an issue though, and isn't normal, since any weight regain should trigger a return of appetite suppression.

Hi Ghoul. Have you tried Perplexity's deep search?

If you haven't, I bet you could get a huge amount of mileage out of it.

Example:


A guy on reddit was selling pro accounts for $20 a year.

(No I don't work for Perplexity or any AI companies. I just got an account and spent hours learning about kidneys, glps, anti-aging from GLPs, etc.)

It digs through the medical journals, summarizes, then links you to sources.

 

[explodingHeart]

I’d suggest hoping off for 2-3 weeks and trying Sema if appetite is your “issue”
I feel 1mg Sema/taking twice a week 0.5/0.5
More than I feel 10mg Tirz taken twice a week 5/5.
On 10mg Tirz I can eat 1500 cals and not feel full. For me Tirz is no where near as good as Sema.
But then again I really only care about minimizing my appetite

I feel the exact same. Tirz was a let down. Combining them seems to help.

While at <= 10% or so bodyfat, if I want to eliminate all hunger and cravings to binge, 5mg sema dosed whenever I feel like it seems to work the best. That's enough to let me fast for a day and not be hungry (not that I reccomend it).

People complain about the side effects of sema, but those side effects are what really help to destroy hunger when you're actually lean.

Tirz just doesn't "hit hard" enough, imo.

 

[Rippidy Dippidy]

I feel the exact same. Tirz was a let down. Combining them seems to help.

While at <= 10% or so bodyfat, if I want to eliminate all hunger and cravings to binge, 5mg sema dosed whenever I feel like it seems to work the best. That's enough to let me fast for a day and not be hungry (not that I reccomend it).

People complain about the side effects of sema, but those side effects are what really help to destroy hunger when you're actually lean.

Tirz just doesn't "hit hard" enough, imo.

Exactly, people often complain it makes them feel nauseous. I use that as a secondary appetite suppressant tbh

 

[Sampei]

Hi Ghoul. Have you tried Perplexity's deep search?

If you haven't, I bet you could get a huge amount of mileage out of it.

Example:
View attachment 318054

A guy on reddit was selling pro accounts for $20 a year.

(No I don't work for Perplexity or any AI companies. I just got an account and spent hours learning about kidneys, glps, anti-aging from GLPs, etc.)

It digs through the medical journals, summarizes, then links you to sources.

Is he still selling it?

 

[AlexDavis43]

Like insulin for type 2 diabetics, and testosterone for hypogonadal men, it's possible to come off of those exogenous hormones via lifestyle changes.

Good grief.

Type 2 diabetics can absolutely come off insulin, Mr GLP1.

Your ChatGPT strategy seems to be phrasing questions to suit your bias. Instead of asking about people who successfully discontinue GLP1s without regaining all the weight, you ask "why do people need to stay on GLP1s forever" and get the answer you're looking for.

Otherwise surely you'd be aware of the cases where they didn't regain all the weight upon GLP1 discontinuation.

 

[Photon]

Hi Ghoul. Have you tried Perplexity's deep search?

If you haven't, I bet you could get a huge amount of mileage out of it.

Example:
View attachment 318054

A guy on reddit was selling pro accounts for $20 a year.

(No I don't work for Perplexity or any AI companies. I just got an account and spent hours learning about kidneys, glps, anti-aging from GLPs, etc.)

It digs through the medical journals, summarizes, then links you to sources.

I wonder how accurate it is.
The chatgpt gpt4 model was giving me numbers and citing sources as well..but if you visit them sources you would see that the figures and numbers do not add up....and alot of the info and figures it gives aren't even in the sources it cites lol.

E.g if the article says strong relationship, it;ll just dump some random number like 95% and give you it..

 

[Photon]

I wonder how accurate it is.
The chatgpt gpt4 model was giving me numbers and citing sources as well..but if you visit them sources you would see that the figures and numbers do not add up....and alot of the info and figures it gives aren't even in the sources it cites lol.

E.g if the article says strong relationship, it;ll just dump some random number like 95% and give you it..

I found out how they're selling it for $20..

Perplexity is giving out alot of free 1 year pro subscriptions to students (you just need a .edu account from certain schools). Previously they were doing this in the US, now it looks like they're giving it out in India. Anyways, they give this free pro subscription via an email voucher. People are buying these vouchers from students and then reselling them on reddit.

There are people on reddit who are reporting that the 1 year pro subscription gets randomly cancelled at 3-6 months. Looks like they're cracking down..slowly lol

I whatsapp'd a couple of sellers on reddit..seems like they're all india numbers.

 

[chmuse]

Good grief.

Type 2 diabetics can absolutely come off insulin, Mr GLP1.

Your ChatGPT strategy seems to be phrasing questions to suit your bias. Instead of asking about people who successfully discontinue GLP1s without regaining all the weight, you ask "why do people need to stay on GLP1s forever" and get the answer you're looking for.

Otherwise surely you'd be aware of the cases where they didn't regain all the weight upon GLP1 discontinuation.

Like insulin for type 2 diabetics, and testosterone for hypogonadal men, it's possible to come off of those exogenous hormones via lifestyle changes.

It is possible. Which is what Ghoul said. See that apostrophe? Are you looking for a reason to be mad, or is it just poor reading comprehension?