GLPs: Anti-Consumption agents, of far more than just food.

[Ghoul]

For those suffering from any condition related to excess consumption, or know someone who is, keep this in mind and consider pointing them in this direction, regardless of weight:

"Anti-consumption agents: Tirzepatide and semaglutide for treating obesity-related diseases and addictions, and improving life expectancy"

https://www.sciencedirect.com/science/article/pii/S0033062024001798

 

[Anonymous35]

Yep not feel depressed or sad at all

 

[Here2Learn]

On Sema I felt duller and had a hard time focusing but I was also exhausted a lot. Felt less of that on Tirz and none on Reta. I have energy and drive and pretty much love the balance of feeling hungry and feeling satisfied faster.

What I am not seeing is any weight loss but just moving up to 6mg today so we will see.

 

[Anat]

There’s a lot of interesting information here. I’ve noticed that ever since I started taking Tirz, the small pleasures in life - like food, entertainment, and gaming - don’t appeal to me as much anymore. Now I feel colder and more calculated. I’m not saying that’s all bad; in fact, it’s helped with business because I don’t get as emotional or worked up as I used to.

 

[Ghoul]

There’s a lot of interesting information here. I’ve noticed that ever since I started taking Tirz, the small pleasures in life - like food, entertainment, and gaming - don’t appeal to me as much anymore. Now I feel colder and more calculated. I’m not saying that’s all bad; in fact, it’s helped with business because I don’t get as emotional or worked up as I used to.

I find my "pleasure quotient" gets satisfied with small. often exquisitely so, amounts of whatever it is.

I extract more enjoyment from "bite sized portions" of very high quality, and much less from "abundance" of quantity. I see it reflected in my shopping habits.

 

[benfrankparkway]

I'll add this regarding the psychological impact. Initially it was proposed a suicide warning be put on the box of Ozempic/Wegovy, but research showed less of a risk than the general population, not more.

Yet there's still conflicting data showing increased and decreased rates of depression. I suspect what's happening is that the sudden loss of food as a reward, from the appetite suppression, occurs before the brain adjusts to no longer need the dopamine hit. So you can't eat, but still feel one of the primary drivers that people experienced causing them to eat. That is, eating relieved depression with a dopamine hit.

Then in time, the brain adjusts, the "addiction" lifts, and along with all the other benefits of weight loss, lessened inflammation, greater mobility, and improved satiety in many things, mood improves, depression lifts, and suicide risk drops below the non-GLP using population.

At least that's what the data seems to suggest. An initial increase in depression(for some who were already depressed and medicating with food), then as time goes on, a steady improvement.

its just anecdotal, by my wife is on week 4 or 2.5mg Tirz. She still eats but has not been snacking at all. One big thing I have been noticing has been her desire to leave the home and go do "stuff". Not anti-social but more rather "I'm good where I am at". She has been more of a homebody this last month. We only went out one time for a date/dinner. I thought it was initially just because she wasn't desiring food, but I asked her to go shopping this week and it was very simple, we got a pair of shoes and a winter jacket, no window shopping or just looking for things just for the sake of it.

She is a hair stylist and has been for 16 years, and there is a huge social aspect to her work, she actually works for her outlet from home, lately she hasnt been showing desire to stay home or schedule more appointments one day so she can be off the next.

 

[Middus]

It's not anhedonia.

20 years since the first GLP prescription
and tens of millions of patient years of clinical experience, along with 15,000,000+ currently prescribed users wouldn't have missed that.

I know what genuine anhedonia is like, and that's not what's induced by GLP.

"Satiety" is a more accurate description.

Excessive gaming is a psychological addiction, hitting the same reward center like gambling, compulsive shopping, or substance addiction, so not surprised to hear the impact to that.

I'm sure plenty of gamers, myself included, have thought in the past "Fuck, I should get off the couch and go do something more interesting / productive / different.".

Let's not speak in absolutes. Semaglutide was reportedly linked to mood issues and anhedonia in some folks.

 

[QuadFather]

Whatever happened to thyroid cancer worries on these? I remember last year it was a concern now it isn’t mentioned really?

 

[Ghoul]

Let's not speak in absolutes. Semaglutide was reportedly linked to mood issues and anhedonia in some folks.

Nothing is absolute. 100 years from now, in retrospect, the picture will be even clearer.

However, there's a strong tendency by those unfamiliar with the long history and widespread use of GLPs to treat them like some high-risk completely novel compound.

The FDA has a robust surveillance system for reports of drug related side effects.

It's not unreasonable to draw conclusions, appropriately weighted according to the volume of evidence, which is enormous in this case.

A sensationalist press breathlessly amplifying "thyroid cancer", "gastroparisis", "pancreatitis", "muscle atrophy", and finally "Ozempic face", would hardly miss the opportunity to report a significant issue with anhedonia or any other non transient psychological problem doctors were encountering.

 

[lukiss96]

Can these agents have lasting or even permanent effects?

I have used them briefly in the past like 3 years ago when they were still fad. Specifically semaglutide.

I have noticed that to this day I just can't eat that much food and get full pretty fast and I can't tolerate red wine like I used to. I just don't like it anymore. This is staple in european diet.

 

[Ghoul]

Can these agents have lasting or even permanent effects?

I have used them briefly in the past like 3 years ago when they were still fad. Specifically semaglutide.

I have noticed that to this day I just can't eat that much food and get full pretty fast and I can't tolerate red wine like I used to. I just don't like it anymore. This is staple in european diet.

No more evidence of that than Insulin or Testosterone having lasting effects once these exogenous hormones are stopped,

However, there is some evidence that the body's metabolic "weight equilibrium" setting, below which appetite increases, and above which appetite diminishes, can adjust over extended periods of time.

So if that were 250lbs, and using these compounds it's kept at 200 for an extended amount of time, according to this hypothesis it may be something closer to 200 even when treatment is stopped.

 

[lukiss96]

No more evidence of that than Insulin or Testosterone having lasting effects once these exogenous hormones are stopped,

Perhaps, but from experience I guess I'm not alone saying that first cycle is where you get and keep majority of your gains so to speak, after that it's a grind the further you use steroids.

 

[Middus]

Nothing is absolute. 100 years from now, in retrospect, the picture will be even clearer.

However, there's a strong tendency by those unfamiliar with the long history and widespread use of GLPs to treat them like some high-risk completely novel compound.

The FDA has a robust surveillance system for reports of drug related side effects.

It's not unreasonable to draw conclusions, appropriately weighted according to the volume of evidence, which is enormous in this case.

A sensationalist press breathlessly amplifying "thyroid cancer", "gastroparisis", "pancreatitis", "muscle atrophy", and finally "Ozempic face", would hardly miss the opportunity to report a significant issue with anhedonia or any other non transient psychological problem doctors were encountering.

True, but stuff like we usually talk about has zero effect on actual direction of research or on FDA decisions based on research. Media usually responds to sensationalist headlines because as I said on the RFK post, media needs to sell. They need money.
The Gastroparesis and other stuff have happened and need to be stated. Just like Ozempic worsened kidney failure in some older folk, and that needed to be noted also. Do they matter? that will eventually depend on how widespread said effects are in the general public. There are studies currently going on to whether ozempic causes a particular type of blindness. These things aren't scare tactics. It's just normal phase IV part of drug development. We are essentially guinea-pigs. GLP-1RAs have already been linked to mood issues, but even weightloss on it's on is linked to mood issues.

 

[Middus]

Can these agents have lasting or even permanent effects?

I have used them briefly in the past like 3 years ago when they were still fad. Specifically semaglutide.

I have noticed that to this day I just can't eat that much food and get full pretty fast and I can't tolerate red wine like I used to. I just don't like it anymore. This is staple in european diet.

Yeah, you may be messed up (I joke). But yup. I had bariatric surgery almost a decade ago. Before surgery I was warned about weird things that may happen to me. Well the weirdest was a switch from hating choc flavoured stuff vs Strawbery flavoured to absolutely detesting strawberry flavoured drinks (and strawberries) but being able to better tolerate chocolate flavoured items. I also felt way less desirefor certain types of drinks, a developed a fizzy water "addiction" despite it being a no-no for post surgery state. The Satiety part may remain or ease up, depending on your body. If you force it, it will go, but why ruin a good thing?

 

[Ghoul]

Perhaps, but from experience I guess I'm not alone saying that first cycle is where you get and keep majority of your gains so to speak, after that it's a grind the further you use steroids.

I've said the same thing. However most people who stop rapidly gain back weight, 90%+ has been reported in the studies looking at that. Hardly an indicator of a durable effect.

What I, many I know, and more recently, clinicians have reported as "observational evidence", is that going back on requires a higher dose to return to the same weight their patients previously achieve on their first round.

I think the most likely reason is immunogenicity, resulting in the immune system rapidly clearing the drug from the body after a break in treatment.

This "immunity" developing to a protein drug after a break is called the "reexposure effect", a widely observed risk in many protein therapeutics.

Granted this is a theory in regards to GLPs, but the trials never anticipated these drugs being used in any other manner than continuously, reaching a maintainance dose and staying there. Over the course of years, there's no drop in efficacy after continuous use.

We can't think of protein/peptide therapeutics in the same way as others. They have a unique set of factors that make the way they work very, very different from "conventional" medicine.

I've argued needlessly jumping on and off, switching, combining, deviating from the pharma schedule, is playing with fire and risking lessening effectiveness of these drugs, potentially for a lifetime.