Tirzepatide: Beyond Appetite Control

[pizzathehutt]

...and really all the other GLP-1 and multi-receptor agonists. For simplicity, I'm focusing on what I have personal experience with, Tirzepatide.

Many get hung up on the appetite suppression benefits of these agonists -- for good and bad.

I believe the narrative needs a shift. In my mind, Tirzepatide’s (and the others) weight loss effects extend beyond simple appetite suppression.

From my understand, these agonists improves insulin sensitivity, increases energy expenditure, enhances lipid metabolism, positively alters gut hormone levels, reduces fat accumulation, possesses anti-inflammatory properties, and improves glycemic control.

All of these combined mechanisms contribute to its overall effectiveness in promoting weight loss and improving metabolic health.

Yes, appetite suppression and caloric deficits is the main player but there's so much more.

Next, I'd like to tie together current public research alongside the wealth of reports across various places to really hone in a solid, data backed, message.

Why? I have friends and colleagues that reject these peptides. Smart folks that have unfortunately accepted narratives that have made even considering usage socially taboo. Folks that could really benefit from them. I'd like them to be around.

 

[Trenbolonetax]

It did for me, but that’s just my experience. I’m having less gastric slowing on Reta than Tirz, also.

Any chance gastric slowing becomes less over time as well at a given dose?

Im keen to use a low dose during a growth phase, appetite suppression has never been a concern for me, the gastric slowing that occurs is however.

 

[Ghoul]

Any chance gastric slowing becomes less over time as well at a given dose?

Im keen to use a low dose during a growth phase, appetite suppression has never been a concern for me, the gastric slowing that occurs is however.

Yes, slowing of digestive motility is one of the means by which the body compels you to take in fewer calories.

GLPs reduce the "target weight", and so that and all the other natural mechanisms to get the animal to stop eating so much are activated.

If you don't want your weight to go any lower, and you're experiencing that effect you need to drop the dose one level. That's how you'd find the "maintenance dose" on pharma.

It takes about 4 weeks to fully adjust to the new level, though most of impact is in the first 2 weeks, Whoever develops a BB protocol for continuous use of GLPs will probobly find the timing is going to be the trickiest part. Since you intend to gain weight, you may need to drop 2 levels. (by level, I mean using the standard pharma dosages, just for convenience). It may turn out the best thing to do is go right to the floor before a bulk. .25mg Sema, 2.5mg Tirz, 2mg Reta.

In my experience appetite rebound is ferocious with a sudden large drop in dose, gastric emptying is turbocharged, and your stomach becomes bottomless. Your senses will make everything seem delicious. An asset while bulking.

Then you need to plan for cutting well in advance, you can't increase in the same large dosage jumps without risking severe, not particularly dangerous, but very unpleasant sides,

This drug is experienced through its side effects. When people say "It stopped working" I find that usually means "I'm not feeling sides, and not losing any more weight" not "At the same dose, I'm steadily gaining weight." None of the long term studies, with people on a stable dose for years have shown that to happen, They've plateaued, the drug is doing what it's supposed to do (in this case, nothing), and to "turn the weight thermostat" lower, higher dose is required.

For the normal users, just stay on the well trodden path. Be patient. If you're at goal weight and still having sides it's time to drop the dose and see where you stabilize at. Once at a maintainance dose, you won't "feel" it again unless you regain weight.

 

[IronMetal_2]

Yes, slowing of digestive motility is one of the means by which the body compels you to take in fewer calories.

GLPs reduce the "target weight", and so that and all the other natural mechanisms to get the animal to stop eating so much are activated.

If you don't want your weight to go any lower, and you're experiencing that effect you need to drop the dose one level. That's how you'd find the "maintenance dose" on pharma.

It takes about 4 weeks to fully adjust to the new level, though most of impact is in the first 2 weeks, Whoever develops a BB protocol for continuous use of GLPs will probobly find the timing is going to be the trickiest part. Since you intend to gain weight, you may need to drop 2 levels. (by level, I mean using the standard pharma dosages, just for convenience). It may turn out the best thing to do is go right to the floor before a bulk. .25mg Sema, 2.5mg Tirz, 2mg Reta.

In my experience appetite rebound is ferocious with a sudden large drop in dose, gastric emptying is turbocharged, and your stomach becomes bottomless. Your senses will make everything seem delicious. An asset while bulking.

Then you need to plan for cutting well in advance, you can't increase in the same large dosage jumps without risking severe, not particularly dangerous, but very unpleasant sides,

This drug is experienced through its side effects. When people say "It stopped working" I find that usually means "I'm not feeling sides, and not losing any more weight" not "At the same dose, I'm steadily gaining weight." None of the long term studies, with people on a stable dose for years have shown that to happen, They've plateaued, the drug is doing what it's supposed to do (in this case, nothing), and to "turn the weight thermostat" lower, higher dose is required.

For the normal users, just stay on the well trodden path. Be patient. If you're at goal weight and still having sides it's time to drop the dose and see where you stabilize at. Once at a maintainance dose, you won't "feel" it again unless you regain weight.

I don't agree with everything ghoul says but this has been my experience. I lost weight quickly without effort on 5mg tirz once a week and am now maintaining on the same dose. I don't feel anything in particular. I just eat like a normal person, no side effect.

 

[Nunya]

Any chance gastric slowing becomes less over time as well at a given dose?

Im keen to use a low dose during a growth phase, appetite suppression has never been a concern for me, the gastric slowing that occurs is however.

I’m not sure I can say I ever experienced much gastric slowing, been pretty regular throughout. BUT, I was eating pretty clean before starting, and one of the BENEFITS has been that now instead of gaining weight by just looking at carbs, I’ve found that I’ve had to UP my carbs. So I’m actually probably getting more fiber in my diet than I was before, now that my body seems to be responding properly to carbohydrates.

It took me a while to figure that out, as a woman approaching meno I’ve had to cut back more and more and more on carbs to just slow the weight gain, and have focused on protein mostly. When I got up to 5mg, I started getting light headed and weak feeling, and so I upped my water first, from 3-4L/day (electrolytes included). But it wasn’t until I upped my carbs that things got going good. It’s so nice to be able to enjoy hot cereal in the morning and some bread at lunch and to not get a face flush from white rice. DEFINITELY a change in response to carbs. My A1c was barely prediabetic before, according to bloodwork, but with my family history and the ‘feels’ I’d get with rice, potatoes, etc. (same feeling I’d get after having a strong IPA) it seemed more than just prediabetic.

I’m no bodybuilder, and I *am* on TRT, but I’ve been on TRT for a few years now. But prior to the last few months, even on TRT, I wasn’t making big gains at the gym, even with a high protein % in my diet. But since being on Tirzepatide, while I’ve lost weight (mostly fat, according to DEXA), I’m CLEARLY building muscle and it’s super f*ckn’ cool. I suspect being able to properly deal with carbohydrates is part of that, but that’s just a guess.

I do not plan to get off this drug - planning on titrating down as @Ghoul mentioned, figuring out where I need to be to maintain OR add lean muscle mass, and keeping track.

 

[juicebro]

These drugs seem to have an effect on dopamine receptor. Has anyone had mood problems, anhedonia, depression etc on them?

 

[Ghoul]

I don't agree with everything ghoul says but this has been my experience. I lost weight quickly without effort on 5mg tirz once a week and am now maintaining on the same dose. I don't feel anything in particular. I just eat like a normal person, no side effect.

They really need to make a pamphlet describing what patients can expect, especially since primary care physicians are prescribing these drugs, because very few people, including clinicians, seem to understand how they work.

I suspect the drug companies didn't want to say "You, obese person with metabolic.disease, have GLP insensitivity or a production deficiency, like a diabetic has with insulin, and like them, will need to be treated for life".

It's already a big hurdle to get "normies" to inject themselves. Some will let themselves die before they do it.

I'll throw this in here as well, bariatric surgery (which will be obsolete soon) doesn't primarily induce weight loss by shrinking the stomach.

When the stomach stretches, it releases GLP receptors, increasing sensitivity to the GLP hormone produced by the intestines. By shrinking it, it stretches more often and the patient's sensitivity to GLP increases.

 

[Sampei]

I envy all of you that don't have much side effects on tirzepatide, a part from the gastric bla bla appetite bla bla, I got the worse shit ever on tirz and it's called 15+ BPM even at 2.5mg.

I inject it and I get +15BPM at rest in less then 24hours, It last until the tirzepatide exit my body completely.

very very annoying.

 

[Ghoul]

I envy all of you that don't have much side effects on tirzepatide, a part from the gastric bla bla appetite bla bla, I got the worse shit ever on tirz and it's called 15+ BPM even at 2.5mg.

I inject it and I get +15BPM at rest in less then 24hours, It last until the tirzepatide exit my body completely.

very very annoying.

Sounds like your Vagus nerve is hypersensitive to GLP.

Perhaps one of the rare downsides to GLP class meds, is that they reduce Heart Rate Variability by activating GLP receptors in the Vagus nerve. This is why heart rate often rises after a large meal, though paradoxically, in some it slows heart rate by the same mechanism.

Believe it or not, for children who have "panic attacks", they advise trying standing on their heads, or apply abdominal pressure, simulating a large meal, to slow heart rate .

A very tiny dose of Atropine counteracts this effect within about an hour. It's found in this anti-diarrhea drug, and can be safely taken at a low dose indefinitely.

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Rarely, some people take large doses to get an opioid like high, and become dependent on it, but obviously if you're not popping handfuls at a time this won't happen, since it takes a huge dose to feel anything like that. It's used as a cheap heroin" in poor countries, just so you're aware.

Anyway, might solve your problem if
you feel like giving it a try.

 

[Sampei]

Sounds like your Vagus nerve is hypersensitive to GLP.

Perhaps one of the rare downsides to GLP class meds, is that they reduce Heart Rate Variability by activating GLP receptors in the Vagus nerve. This is why heart rate often rises after a large meal, though paradoxically, in some it slows heart rate by the same mechanism.

Believe it or not, for children who have "panic attacks", they advise trying standing on their heads, or apply abdominal pressure, simulating a large meal, to slow heart rate .

A very tiny dose of Atropine counteracts this effect within about an hour. It's found in this anti-diarrhea drug, and can be safely taken at a low dose indefinitely.

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Rarely, some people take large doses to get an opioid like high, and become dependent on it, but obviously if you're not popping handfuls at a time this won't happen, since it takes a huge dose to feel anything like that. It's used as a cheap heroin" in poor countries, just so you're aware.

Anyway, might solve your problem if
you feel like giving it a try.

I don't get any HR increase from semaglutide

 

[Ghoul]

I don't get any HR increase from semaglutide

I don't get any HR increase from semaglutide

I'm not an advocate of switching compounds for no good reason, but in this case, maybe try Reta because the benefits of GIP are valuable. I know it has a rep for raising heart rate in some, but there are always paradoxical responders where that doesn't happen, or it does the opposite.

 

[Sampei]

I'm not an advocate of switching compounds for no good reason, but in this case, maybe try Reta because the benefits of GIP are valuable. I know it has a rep for raising heart rate in some, but there are always paradoxical responders where that doesn't happen, or it does the opposite.

But doesn't reta have some of the same stuff in Tirz? So I should probably get the same effect. Sema doesn't give me any HR because doesn't have any GIP isn't it?

 

[Ghoul]

But doesn't reta have some of the same stuff in Tirz? So I should probably get the same effect. Sema doesn't give me any HR because doesn't have any GIP isn't it?

Your point is reasonable, and may be accurate. However, GLP is the main driver of changes to the way the Vagus nerve affects heart rate.

GLP in Tirz doesn't function exactly the same way as it does in Sema. In Reta, it may be somewhat different than the other two.

I don't know that your heart rate problem is being caused by GIP, but maybe it's from this difference in the Tirz version of GLP affecting that nerve more strongly.

Most of the non-weight related health benefits are associated with GLP, not GIP, so you're fine with Sema. I just like the potent liver protective effects of GIPs, and trying. Reta for that might make sense, though it's a damned expensive option for indefinite use if you need the max dose of 12mg for maintenance.

Look at the effects of GLP on heart rate, up, down, or nothing, lol.

 

[Sampei]

Your point is reasonable, and may be accurate. However, GLP is the main driver of changes to the way the Vagus nerve affects heart rate.

GLP in Tirz doesn't function exactly the same way as it does in Sema. In Reta, it may be somewhat different than the other two.

I don't know that your heart rate problem is being caused by GIP, but maybe be from this difference in the Tirz version of GLP affecting that nerve more strongly.

Most of the non-weight related health benefits are associated with GLP, not GIP, so you're fine with Sema. I just like the potent liver protective effects of GIPs, and trying. Reta for that might make sense, though it's a damned expensive option for indefinite use if you need the max dose of 12mg for maintenance.

Look at the effects of GLP on heart rate, up, down, or nothing, lol.


View attachment 298842

Do you have a charts on all the main benefit of GIP and GLP and maybe one Vs the other?

Yeah reta Is too damn expensive at the moment.

I wonder if the Tirz HR would fix itself after maybe 6 months of use.

It's amazing how strong it affects me, it gives me +15 BPM after few hours I have injected it and it stays there..even 2.5mg gives me that much of an HR increase

 

[Xplicit]

Yes, slowing of digestive motility is one of the means by which the body compels you to take in fewer calories.

GLPs reduce the "target weight", and so that and all the other natural mechanisms to get the animal to stop eating so much are activated.

If you don't want your weight to go any lower, and you're experiencing that effect you need to drop the dose one level. That's how you'd find the "maintenance dose" on pharma.

It takes about 4 weeks to fully adjust to the new level, though most of impact is in the first 2 weeks, Whoever develops a BB protocol for continuous use of GLPs will probobly find the timing is going to be the trickiest part. Since you intend to gain weight, you may need to drop 2 levels. (by level, I mean using the standard pharma dosages, just for convenience). It may turn out the best thing to do is go right to the floor before a bulk. .25mg Sema, 2.5mg Tirz, 2mg Reta.

In my experience appetite rebound is ferocious with a sudden large drop in dose, gastric emptying is turbocharged, and your stomach becomes bottomless. Your senses will make everything seem delicious. An asset while bulking.

Then you need to plan for cutting well in advance, you can't increase in the same large dosage jumps without risking severe, not particularly dangerous, but very unpleasant sides,

This drug is experienced through its side effects. When people say "It stopped working" I find that usually means "I'm not feeling sides, and not losing any more weight" not "At the same dose, I'm steadily gaining weight." None of the long term studies, with people on a stable dose for years have shown that to happen, They've plateaued, the drug is doing what it's supposed to do (in this case, nothing), and to "turn the weight thermostat" lower, higher dose is required.

For the normal users, just stay on the well trodden path. Be patient. If you're at goal weight and still having sides it's time to drop the dose and see where you stabilize at. Once at a maintainance dose, you won't "feel" it again unless you regain weight.

Ghoul thank you very much for such an in depth reply. Incredibly informative and I appreciate you sharing your thoughts on the topic.

I will second your words on gastric emptying turbo charged when coming off these GLPs. I was not prepared for it the first time and set myself back a few % of bodyfat until it calmed down. Based off that experience, I now taper off GLPs instead of cold turkey and have better success with the transition.

 

[MrTexas2]

I started Zepbound (script, I pay zero w/ my insurance) because my weight just keeps creeping up as I get older. I was 11% b fat at 212 and am now 16.2 at 230. My blood pressure has elevated w/ the extra weight. Started 3 days ago.

I am only in injecting 2.5 mgs e7d and feel nothing, absolutely no sides and no loss in appetite. Wife has lost 6 lbs in a touch over 2 weeks and complains of many sides.

 

[Ghoul]

I started Zepbound (script, I pay zero w/ my insurance) because my weight just keeps creeping up as I get older. I was 11% b fat at 212 and am now 16.2 at 230. My blood pressure has elevated w/ the extra weight. Started 3 days ago.

I am only in injecting 2.5 mgs e7d and feel nothing, absolutely no sides and no loss in appetite. Wife has lost 6 lbs in a touch over 2 weeks and complains of many sides.

Women react more strongly due to a lower density of GLP receptors vs males, and effect strength appears correlated with total receptor saturation.

Side effects are mostly associated with "eating beyond your hunger", and out of habit. Because there's a delay between eating and the sides, it takes some time to "learn" that lesson.

Small portions, then wait to see how it goes before eating again, and a glass of metamucil go a long way towards alleviating sides.

 

[lift4lyfe]

For the normal users, just stay on the well trodden path. Be patient. If you're at goal weight and still having sides it's time to drop the dose and see where you stabilize at. Once at a maintainance dose, you won't "feel" it again unless you regain weight.

Any downside to 24/7 GIP/GCGR agonism in the long term? Besides the heart rate stuff, we don't know for sure whether there's a negative to agonizing these receptors 24/7, right?

 

[Ghoul]

Any downside to 24/7 GIP/GCGR agonism in the long term? Besides the heart rate stuff, we don't know for sure whether there's a negative to agonizing these receptors 24/7, right?

Sure we do. There's always a baseline of these hormones present agonizing receptors. Levels decrease after a period of fasting, increase after eating.

Using arbitrary numbers:.

On a scale of 1-10, at 10, appetite is fully satiated and the body begins to exert "anti-eating effects" like slowing digestion and making food seem unpalatable.

-Your baseline level of these hormones is 3.

-After eating xx volume of food levels rise to 7.

--------

You use a long lasting GLP class drug.

-Now your baseline is 5.

-After eating the same volume of food the level rises to 10, and you can't eat another bite.

-After a while the food is no longer stimulating hormone production and you drop back to 5.

GLP drugs have been around for 30 years; without any negative effects associated with a long term higher level of the hormone.. On the contrary, the diabetics originally using the early, daily, short half life version of GLP drugs for years had less development of disease and outlived, in general, their non diabetic counterparts.

 

[Ghoul]

These drugs seem to have an effect on dopamine receptor. Has anyone had mood problems, anhedonia, depression etc on them?

For a moment there was a belief increased rates of suicide were associated with the drug, which has been since disproven.

While I wouldn't characterize it as "anhedonia", I will say that the pleasure reinforcing a whole host of compulsive behaviors seems to drop dramatically.

After a period of adjustment, the pleasure in other, non-compulsive behaviors seems to increase, in my experience. The guilt inducing "bad habits" that always seemed so satisfying, despite the conscious mind protesting, just lose their influence to a great extent.

The anecdotes and my personal observation of people suddenly dropping things, from substances to bad relationships, has gone from "odd coincidence" to growing mountain of evidence.

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My hypothesis is that the mechanisms of energy intake have, out of necessity, evolved to exert such a powerful influence over behavior, whether an addiction can take hold or not is dependent on its ability to hijaak the same parts of the brain that compel us to eat.

 

[Nunya]

While I wouldn't characterize it as "anhedonia", I will say that the pleasure reinforcing a whole host of compulsive behaviors seems to drop dramatically.

After a period of adjustment, the pleasure in other, non-compulsive behaviors seems to increase, in my experience. The guilt inducing "bad habits" that always seemed so satisfying, despite the conscious mind protesting, just lose their influence to a great extent.

This has been my experience. I take a LOT more pleasure in non-compulsive behaviors that I have to work hard for (like working out, for example) than I used to, and virtually no pleasure in compulsive behaviors (even cuticle picking, long a habit of mine, has significantly decreased).