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.

 

[pizzathehutt]

I personally have some mechanism statements I'd like to explore and identify if they are true or not -- and what the data looks like. Some of this has already been proven. Some may need clarification or analysis into if it's really doing something or not.

• Improved Insulin Sensitivity:
  • Tirzepatide enhances insulin sensitivity, which helps the body utilize glucose more effectively, reducing the likelihood of excess glucose being stored as fat. More on that below.
• Enhanced Lipid Metabolism, Reduction in Fat Accumulation, and Basal Metabolic Rate:
  • Tirzepatide affects lipid metabolism by promoting fat oxidation and reducing fat storage, leading to a reduction in body fat.
  • Tirzepatide promotes the breakdown of stored fat (lipolysis) by enhancing the activity of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). This leads to the mobilization and reduction of fat stores.
  • It decreases the process of lipogenesis (the creation of new fat cells), which is often driven by high levels of insulin and glucose. By stabilizing blood sugar levels and improving insulin sensitivity, tirzepatide indirectly reduces the creation of new fat cells.
  • Tirzepatide significantly improves glycemic control, stabilizing blood sugar levels and reducing the risk of insulin spikes that can lead to fat storage.
  • Tirzepatide can increase basal metabolic rate, which means more calories are burned at rest. This effect contributes to a higher overall energy expenditure, leading to reduced fat storage.
• Anti-Inflammatory Properties:
  • Tirzepatide’s dual receptor agonist action has anti-inflammatory effects that help reduce chronic inflammation, which is associated with obesity and metabolic diseases.

 

[AlexDavis43]

90% comes down to fat loss. Call that short-sighted if you like, but show me any of these benefits occur in an energy surplus where you're gaining body fat.

Maybe some of the negative effects of fat gain are attenuated, but the main benefits of these drugs is fat loss and downstream from there.

 

[JG91]

What mechanism causes the increase in BMR? And any idea how significant it is?

 

[AlexDavis43]

What mechanism causes the increase in BMR? And any idea how significant it is?

The heavy lifting is done by reduced food intake. A minor boost in BMR is nothing compared to 100s less kcals from food intake.

 

[TA13579]

Is there a specific macro ratio that is best for Tirz protocol? Keto? High Protein Low carb? Does macro ratio matter if cals are kept at a deficit when running tirz?

 

[Trenbolonetax]

Is there a specific macro ratio that is best for Tirz protocol? Keto? High Protein Low carb? Does macro ratio matter if cals are kept at a deficit when running tirz?

My opinion, is that if you’re trying to absolutely maximize fat loss, while also not just fasting, protein plus bare minimum fat.

 

[Trenbolonetax]

I personally have some mechanism statements I'd like to explore and identify if they are true or not -- and what the data looks like. Some of this has already been proven. Some may need clarification or analysis into if it's really doing something or not.

• Improved Insulin Sensitivity:
  • Tirzepatide enhances insulin sensitivity, which helps the body utilize glucose more effectively, reducing the likelihood of excess glucose being stored as fat. More on that below.
• Enhanced Lipid Metabolism, Reduction in Fat Accumulation, and Basal Metabolic Rate:
  • Tirzepatide affects lipid metabolism by promoting fat oxidation and reducing fat storage, leading to a reduction in body fat.
  • Tirzepatide promotes the breakdown of stored fat (lipolysis) by enhancing the activity of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL). This leads to the mobilization and reduction of fat stores.
  • It decreases the process of lipogenesis (the creation of new fat cells), which is often driven by high levels of insulin and glucose. By stabilizing blood sugar levels and improving insulin sensitivity, tirzepatide indirectly reduces the creation of new fat cells.
  • Tirzepatide significantly improves glycemic control, stabilizing blood sugar levels and reducing the risk of insulin spikes that can lead to fat storage.
  • Tirzepatide can increase basal metabolic rate, which means more calories are burned at rest. This effect contributes to a higher overall energy expenditure, leading to reduced fat storage.
• Anti-Inflammatory Properties:
  • Tirzepatide’s dual receptor agonist action has anti-inflammatory effects that help reduce chronic inflammation, which is associated with obesity and metabolic diseases.

One of the very cool things about Tirz is that while it can enhance insulin secretion, the big deal is the ability of it to improve insulin independent glucose clearance. It’s the combo of these I believe that enables it to work as a direct insulin sensitizing agent; it’s not just having you pump out more insulin.

It interacts differently with adipocytes based on fed / fasted state via the GIPR agonism. Interesting stuff.

 

[Ghoul]

I know many here have moved beyond their initial dismissal of GLP class peptides, but the evidence of non-weight loss benefits have been long standing, going back over 30 years. Most of the GLP receptors throughout the body have nothing to do with weight loss:

The breakthrough in recent years was making GLP and GIP with a half life of more than just a few seconds.

There is simply not enough research capacity to pursue every tangential benefit at the same time. The most profitable areas will of course be first.

https://www.sciencedirect.com/science/article/abs/pii/S1043276016301266#:~:text=GLP%2D1%20receptor%20agonists%20activate,volume%20and%20ischemia%2Dinduced%20damage.

That said, stop trying to convince idiots to start using something that will extend their lives. Let nature take its course.

 

[Trenbolonetax]

I know many here have moved beyond their initial dismissal of GLP class peptides, but the evidence of non-weight loss benefits have been long standing, going back over 30 years. Most of the GLP receptors throughout the body have nothing to do with weight loss:

The breakthrough in recent years was making GLP and GIP with a half life of more than just a few seconds.

There is simply not enough research capacity to pursue every tangential benefit at the same time. The most profitable areas will of course be first.

View attachment 298626

https://www.sciencedirect.com/science/article/abs/pii/S1043276016301266#:~:text=GLP%2D1%20receptor%20agonists%20activate,volume%20and%20ischemia%2Dinduced%20damage.

That said, stop trying to convince idiots to start using something that will extend their lives. Let nature take its course.

Not sure if directed at me? I’m not trying to convince anyone of anything. Just sharing my experience and providing some commentary on the portions that I find fascinating.

 

[Ghoul]

Not sure if directed at me? I’m not trying to convince anyone of anything. Just sharing my experience and providing some commentary on the portions that I find fascinating.

I was responding to the OP and his efforts to convince others.

 

[Trenbolonetax]

I was responding to the OP and his efforts to convince others.

Ah, understood. I agree. If people are so dense that they can’t see the clear benefit of using some of these GLP1s outside of just weight loss, I’m inclined to believe they have done zero research on their own.

It’s all there. Human studies. Rat studies. Some of the rat studies are really interesting because it illuminates some of the mechanisms of action that the human studies do not touch on whatsoever.

And destroys the argument that these health benefits are only mediated via weight loss.

There is a reason my A1C was 5.1 and fasting insulin was 2.5 on 27iu of GH. With the best blood work I've ever had in my fucking life, by far. I was astounded.

 

[BuildABro]

I have only tried Tirzepatide once and it did not agree with me. I felt sick like a had a stomach flu basically. It was not pleasant. Got the kit from Tracy and ended up selling the rest of it off. I am not a fan of Clen or albuterol either which I know many swear by.

Maybe if I was in serious need of cutting, which could happen at some point in the future (hopefully), then I could potentially try to revisit but such compounds just don't line up with my current goals.

 

[Trenbolonetax]

I have only tried Tirzepatide once and it did not agree with me. I felt sick like a had a stomach flu basically. It was not pleasant. Got the kit from Tracy and ended up selling the rest of it off. I am not a fan of Clen or albuterol either which I know many swear by.

Maybe if I was in serious need of cutting, which could happen at some point in the future (hopefully), then I could potentially try to revisit but such compounds just don't line up with my current goals.

Next time you're gonna try something, I HIGHLY recommend Reta.

Just start nice and low. Really nice and low. Slowly escalate and I'm willing to bet a pretty penny you can ameliorate a lot of the issues you experienced.

Reta is more likely to give me heart burn, whereas Tirz is more likely to give me stomach issues.

 

[BuildABro]

Next time you're gonna try something, I HIGHLY recommend Reta.

Just start nice and low. Really nice and low. Slowly escalate and I'm willing to bet a pretty penny you can ameliorate a lot of the issues you experienced.

Reta is more likely to give me heart burn, whereas Tirz is more likely to give me stomach issues.

Thanks for the tip, but I would be extremely wary as I really need my calories right now as I am on a bulk. And I obviously do plenty of tinkering with my hormones already to take on additional polypharma just for the hell of it.

Maybe at some point down the line.

 

[Trenbolonetax]

Thanks for the tip, but I would be extremely wary as I really need my calories right now as I am on a bulk. And I obviously do plenty of tinkering with my hormones already to take on additional polypharma just for the hell of it.

Maybe at some point down the line.

Oh, no, not on a bulk. Not what I'm saying. When that point down the line comes where you want to shred up a bit is what I'm referring to.

 

[BuildABro]

Oh, no, not on a bulk. Not what I'm saying. When that point down the line comes where you want to shred up a bit is what I'm referring to.

I am hopeful to get to that point for sure. I need to hit 200 pounds first, then in 2025 I am going to take a run at getting to sub 10% BF. Not a level I have ever hit so I mainly went to do it to prove to myself that I can.

 

[Ghoul]

For those not aware, and I blame the drug companies and docs for not explaining this dynamic, once you're on a maintenance dose, that is weight and dose are in balance, you no longer feel any appetite suppression. You feel nothing.

It's like hitting a stable TRT dose after a couple of months. You feel effects with each dose on the way up, but once blood levels are stable and T levels off. you don't feel anything but "normal". That's why a long term, titrate up, at your goal weight settle on a maintenance dose, plan from the start, is the way to use these properly in my opinion.

You maintain the other health benefits of GLP/GIP levels being higher than you would normally produce despite no longer losing weight, and avoid the potential risk of losing future effectiveness from stopping and restarting later.

Even for bodybuilders with only intermittent need for suppression. You can dial back the dose a few weeks before bulk and regain weight, then crank it back up for a cut. After a while you should be able to determine "At X mg I'll end up at xxx lbs" because appetite suppression quickly tapers off and stops.

 

[Xplicit]

For those not aware, and I blame the drug companies and docs for not explaining this dynamic, once you're on a maintenance dose, that is weight and dose are in balance, you no longer feel any appetite suppression. You feel nothing.

It's like hitting a stable TRT dose after a couple of months. You feel effects with each dose on the way up, but once blood levels are stable and T levels off. you don't feel anything but "normal". That's why a long term, titrate up, at your goal weight settle on a maintenance dose, plan from the start, is the way to use these properly in my opinion.

You maintain the other health benefits of GLP/GIP levels being higher than you would normally produce despite no longer losing weight, and avoid the potential risk of losing future effectiveness from stopping and restarting later.

Even for bodybuilders with only intermittent need for suppression. You can dial back the dose a few weeks before bulk and regain weight, then crank it back up for a cut. After a while you should be able to determine "At X mg I'll end up at xxx lbs" because appetite suppression quickly tapers off and stops.

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.

 

[Intrepid]

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 haven't noticed a decrease personally

but i do find that digestive enzymes (invest in a good comprehensive one) and a prebiotic+probiotic do help to prevent bloating when pushing the calories higher when using GLP-1s