Giant Semaglutide Thread (and other GLP-1 / GIP agonists)

[Doodle]

Wanted to create a thread where everyone can post their experiences with different sourced Semaglutide.

Who are you using?
Pharma vs non?
Dosage?
How long have you been taking it?
What are your thoughts?
Have you lost weight?
Side effects?
Oral vs injection?
Tests?

 

[clearheaded]

Some very basic googling will “logically” tell you why it causes cancer in rats and not in humans but let me help. “Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation.” Could it actually be you who has no idea what they’re talking about?

https://www.ccjm.org/content/ccjom/82/3/142.full.pdf

I mean it literally lists a bunch of cancer that have glp receptors... which is whatever... but he was talking about no logical reason.. which there is.. infact if read your article it talks about 4.3X risk of cancer in a glp in humans.... also says "difficult to know cancer risk" but probably low.. thats the tested ones...so before you think ur gunna have a drop mic moment, perhaps consider what authors say ie they don't know...

just remember usually when start seeing signals of course drug companies pay for studies to say naa...

AGAIN point was simply taking unapproved drug that has plenty of potential to have cancer as a side effect esp since acts on other receptors is unwise...

if have been alive long enough you should know there is no free lunch and side effects and knowledge of even how or why these drugs work often changes...

Big pharma does do great things I agree, but lets be honest there is some shady shit on the best of days...

as great man once said
"to back to reddit-Tracy"

 

[DanishPanther]

I mean it literally lists a bunch of cancer that have glp receptors... which is whatever... but he was talking about no logical reason.. which there is.. infact if read your article it talks about 4.3X risk of cancer in a glp in humans.... also says "difficult to know cancer risk" but probably low.. thats the tested ones...so before you think ur gunna have a drop mic moment, perhaps consider what authors say ie they don't know...

just remember usually when start seeing signals of course drug companies pay for studies to say naa...

AGAIN point was simply taking unapproved drug that has plenty of potential to have cancer as a side effect esp since acts on other receptors is unwise...

if have been alive long enough you should know there is no free lunch and side effects and knowledge of even how or why these drugs work often changes...

Big pharma does do great things I agree, but lets be honest there is some shady shit on the best of days...

as great man once said
"to back to reddit-Tracy"

It's all nonsense, what you talk about has been disproven long ago!

As sally says ...

 

[DanishPanther]

Fundamentally, these drugs work by fooling the brain into thinking that the body's setpoint is down there v, not up here ^.

They're so effective because the body defends its setpoints vigorously: it does trickery to make you eat less and move more--even unconsciously--if you, say, had put on a few lbs over Christmas and overshoot your setpoint. It also does that the other way around, e.g. when you've lost 10% of your body weight on a diet and it thinks you need to refill empty coffers.

There is a significant evidence that the brain takes years or longer to re-adjust how it responds to nutrients based on a prior setpoint--i.e. appetite, sense of smell, and cravings all remain elevated after weight loss, because that prior high setpoint keeps being defended by the brain.

But then being overweight or obese does some sneaky things while you're fat that sabotage the process of resetting that point by maintaining a consistent weight.

E.g. the skeleton does a bunch of leptin signalling work; that bish doesn't turn over for about a decade. Being fat also trashes GH levels maybe-permanently, esp in women, which has an impact on daily energy levels (see also: aging). Exercise during weight loss turns out to lower RMR further than weight loss alone, and it doesn't bounce back even when checked 5 years later, so a cheat day is that much more derailing.

And a bunch more things, too, but you get the idea.

So once you get skinny, you need to not only have diet and exercise dialed in to a lower RMR than you had from before getting fat, but it may take years to get to the point where it feels to the brain like not being on an extreme diet all the time. Ugh.

Building muscle helps with some of this, of course, but not all of it. Suffice to say many skinny people who were fat for more than a few years are just not the same physiologically as people who never got fat in the first place.

For some it's likely it will take years for after reaching a goal weight for their body to adjust the new lower setpoint that it can defend as zealously as it defended the higher one. If ever, for some.

Hence the idea of "maintenance dose."

Finally, someone who gets it!

It's not just psychological; though for many the reason they got fat the first time, was because they "southed" themselves due to stress or some personal trauma.

As for tactics, we still have the meds to use for years after we get down there.
The Nova studies showed it took 5 years for most of the participants to stop with the meds before they were back at where they started.
It does not happen in weeks or months but in years.

So etc. dieting a few months a year on these meds could be enough to keep the weight down there for the decades it takes to "reset" should be duable.
(fat cells produce leptin, and being fat enough, you have produced loads of fat cells that take years to die).

And obviously, lower weight mean you can be more active ... alone loss in weight lowers BMR allot otherwise.
Lastly a period with t4 mono theraphy around/little above maintance might be smart.

 

[DanishPanther]

Pharma titration is 4 weeks per step. Many stay at a dose longer: until blood sugar control or appetite suppression wanes. Clinical guidelines past 5mg is to titrate after it's been a month of no weight loss.

Dividing is ... divisive. Some swear by it. My theory is that tolerance can get built one of two ways: by metabolizing the drug more efficiently, or by growing new receptors to compensate for increased binding. If the latter, then dividing may actually hurt since there's no "downtime" near the end of a dose to help discourage that tolerance-building.

The pharma schedule works; no strong reason not to use it.

Same as other weight-loss you should shoot for ~0.5-1kg a week. Faster puts strain on the liver and kidneys excreting fat and whatever else the body stashed in your fat cells for safe keeping.

This advice is probably good for many normal people!

Esp if you want to lose weight by eating rather ad libitum.
In these studies, they get a little general health coaching on how to live healthier, but it's mostly people who have problems with dieting and training, to begin with, and they don't get a diet or a training program nor diet or training paradigm.

Instead of a plan, they titrate their way down to the chosen kcal deficit, using the meds to do this.

Have to say I disagree that this is given to be the best way to use these meds (esp. for people like those in here).

Also the idea of 0,5-1 kg for obese people I consider a general myth; there are pros and cons when it comes to losing it faster, but the fatter you are, the more okay it is to lose it faster.

Lyle Mcdonald has like 100.000 people that has used his RFL by now, and there is very few medical problems (even considered or compared to people that is dieting normally) and in fact there is allot of medically wtf effects (so many that Michael Mosley started putting all his fat clients on a 800 kcal diet).

Dr Michael Mosley: The experts agree - this 800-calorie diet works

The main reason this speed is chosen is to ensure compliance!
Nova and Lilly want a high compliance percentage in their studies.

In general, the 0,5-1 kg is also made to secure enough nutrition, assuming people will eat loads of "crap" ... but etc. Nupo is certified to allot bigger deficit, with intake around 600 kcals (their new studies with sema, show a gigant deficit for 12 weeks, with 2 weeks break between, is fine) ... and you can make you own protein diet much more nutritious than theirs easily with a few subs... it's mostly a question of getting so little protein of so low quality that people have died in the past.

There is a risk for kidney stones, but generally, it's mostly in fightting athletes (they way they train) that cause those problems with the kidney and liver, and it quickly returns to normal.

In quick fat loss on fat ppl, on the contrary:

Changes in hepatic and renal outcomes were variable but generally led to either no change or improvements in either of these.

The effect of very low-calorie diets on renal and hepatic outcomes: a systematic review

Very low-calorie diets (VLCDs) are an effective means by which to induce clinically significant weight loss. However, their acceptance by health care practitioners and the public is generally lower than that for other nonsurgical weight loss methods. ...

www.ncbi.nlm.nih.gov

A better approach for many in here would seem to dial in your kcal deficit and training up front, then titrate runningly, until and for as long as you can sustain it ... with sema many show better results with 2 x a week, 2 x 0,5 seems to work on many following this approach for a long time (more than 12 weeks) - a famous professional body builder coach we all know, use that for prep on many of his athletes very successful.

 

[clearheaded]

It's all nonsense, what you talk about has been disproven long ago!

As sally says ...

uh? I literally used what they said in the literature she posted? don't fool yourself, taking approved meds can cause issue never mind UN approved drugs ESP that they are acting on different receptors.

I guess this is a case when people read a tiny amount and ignore the rest AND what the AUTHORS actually said as a conclusion.

hilarious everything people disagree with even with no logic involved is MSM...

"There is a risk for kidney stones, but generally, it's mostly in fightting athletes (they way they train) that cause those problems with the kidney and liver, and it quickly returns to normal."

where do u get this from? "only in fighters"... what about the case studies showing renal failure in people taking ozempic that is permanent? Do you know Drs WONT put you on ozempic if have renal issues form diabetes? So what in your expert opinion causes the issues with kidneys? your saying its NOT from loosing too much weight too fast? than what?

Anyway, just remember me in 10-15 years when more serious side effects show up... there is no free lunch... certainly obese pre diabetic may show benefit as heading to a sooner death... but what about healthy people who just want to loose some weight? maybe there is a reason they need you do be above 30BMi to RX...

but again, my point is even science is not agreed on approved GLP... its a pretty big leap saying Reza is safe even before its even approved.

what's crazy is folks LOVE unapproved meds when it fits their wants. But prob say F big pharma for trumps warp speed vax...

anyhoo, do as u wish, just wanted to point out some flaws in your logic.

 

[DanishPanther]

...

Sorry, but I'm unable to comprehend what you just wrote.
If you want to write it as an adult, I'll give it another go.

Otherwise, .blocked, .delete.

 

[clearheaded]

lol classic millennial... think prove something, quote what they posted saying it says something different... "blah bah blah I cant hear you"

 

[AlexDavis43]

Fundamentally, these drugs work by fooling the brain into thinking that the body's setpoint is down there v, not up here ^.

They're so effective because the body defends its setpoints vigorously: it does trickery to make you eat less and move more--even unconsciously--if you, say, had put on a few lbs over Christmas and overshoot your setpoint. It also does that the other way around, e.g. when you've lost 10% of your body weight on a diet and it thinks you need to refill empty coffers.

There is a significant evidence that the brain takes years or longer to re-adjust how it responds to nutrients based on a prior setpoint--i.e. appetite, sense of smell, and cravings all remain elevated after weight loss, because that prior high setpoint keeps being defended by the brain.

But then being overweight or obese does some sneaky things while you're fat that sabotage the process of resetting that point by maintaining a consistent weight.

E.g. the skeleton does a bunch of leptin signalling work; that bish doesn't turn over for about a decade. Being fat also trashes GH levels maybe-permanently, esp in women, which has an impact on daily energy levels (see also: aging). Exercise during weight loss turns out to lower RMR further than weight loss alone, and it doesn't bounce back even when checked 5 years later, so a cheat day is that much more derailing.

And a bunch more things, too, but you get the idea.

So once you get skinny, you need to not only have diet and exercise dialed in to a lower RMR than you had from before getting fat, but it may take years to get to the point where it feels to the brain like not being on an extreme diet all the time. Ugh.

Building muscle helps with some of this, of course, but not all of it. Suffice to say many skinny people who were fat for more than a few years are just not the same physiologically as people who never got fat in the first place.

For some it's likely it will take years for after reaching a goal weight for their body to adjust the new lower setpoint that it can defend as zealously as it defended the higher one. If ever, for some.

Hence the idea of "maintenance dose."

Thanks for posting this. It's a very nuanced and complicated set of problems, the closer you look.

 

[DanishPanther]

lol classic millennial... think prove something, quote what they posted saying it says something different... "blah bah blah I cant hear you"

You are not making much sense.

I have told you who ordered the study on cancer and Semaglutide.
I have shown you they were conducted and the meta-analysis paid by those who wanted to show it could lead to cancer ended up concluding it's super safe and that cancer is no risk at all.

You can read the newest and biggest meta-review here:
https://pubmed.ncbi.nlm.nih.gov/37531876/

I quote: Semaglutide and cancer: A systematic review and meta-analysis

Conclusion: Semaglutide use in RCTs and real-world studies was not associated with an increased risk of any types of cancer, and this conclusion is supported by a high grade of evidence.

Novo Nordic even estimates that in the future 80% over the age of 50 will get better and longer lives being on the drug than not.

It's easy to give mouse or rat cancers (I have worked enough in a lab to tell you that), you can do that by basically any substance.

As SillySally wrote:

Some very basic googling will “logically” tell you why it causes cancer in rats and not in humans but let me help. “Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation.” Could it actually be you who has no idea what they’re talking about?

https://www.ccjm.org/content/ccjom/82/3/142.full.pdf

As for kidney and liver health when you lose weight FAST, I've read ALL the studies.
Those that show kidney damage, are mostly those done on fighters losing up to 20 kg in a week! (read: it's due to diarectics and low fluid intakes dehydrating on purpose while working out insanely), and even in those studies, they recover full kidney function super fast.

In many other studies, including this one:
Most subjects IMPROVED kidney function by losing weight FAST.

The effect of very low-calorie diets on renal and hepatic outcomes: a systematic review

Changes in hepatic and renal outcomes were variable but generally led to either no change or improvements in either of these.

But sure, kidney stones are a real risk of losing weight fast, but guess what, they are when you are obese to begin with, so the risk is not elevated more than it was, to begin with!

 

[Sumz]

Is unconstituted tirzepatide safe for storage at room temp?

 

[UncleBuns]

Is unconstituted tirzepatide safe for storage at room temp?

Yes. Keep it out of sunlight. If you're going to do long-term storage like years, fridge or freezer.

 

[DanishPanther]

Just saw this on Twitter, might be Interesting to some of you.
Semaglutide is making operations absolute.

 

[TessaM]

Just saw this on Twitter, might be Interesting to some of you.
Semaglutide is making operations absolute.

The fact that we used to infect obese people with tapeworms, give them pills full of explosive powder, or cut out parts of their stomachs will all be relegated to horrified campfire tales about the dark ages of medicine.

Not leeches tho; those are making a comeback!

 

[DanishPanther]

The fact that we used to infect obese people with tapeworms, give them pills full of explosive powder, or cut out parts of their stomachs will all be relegated to horrified campfire tales about the dark ages of medicine.

Not leeches tho; those are making a comeback!

True, have you seen this as well btw:

Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial - Nature Medicine

Tirzepatide is being used to help patients who already achieved meaningful weight reduction through intensive lifestyle efforts, to keep their weight off permanently (and it seems to be working).

I get that most bodybuilders won't like it; goes against the testosterone-driven macho element of the sport and the stigma of “not being able to handle it”.

*stole it from Owen Murphy on Lyles page.

But for everyone else, it's certainly an interesting time in history to be fat.

 

[Mongo966]

The fact that we used to infect obese people with tapeworms, give them pills full of explosive powder, or cut out parts of their stomachs will all be relegated to horrified campfire tales about the dark ages of medicine.

Not leeches tho; those are making a comeback!

It's a good point though.
People in the first world have been willing to try just about anything to help them lose weight.
Nobody wants to be obese but nobody wants to be hungry either. If you're hungry all the time, you're going to eat too much, gain weight, and you're going to suffer socially and medically. It's a curse.
But now we have a medicine for it...finally!!
The impact it's going to have on society in general...
I don't think we can understate how big of a deal this is.
It's fucking huge.

 

[Mongo966]

I don't think we can understate how big of a deal this is.

overstate*
durr

 

[UncleBuns]

The fact that we used to infect obese people with tapeworms, give them pills full of explosive powder, or cut out parts of their stomachs will all be relegated to horrified campfire tales about the dark ages of medicine.

Not leeches tho; those are making a comeback!

Leeches are legit! Maggots are still used medically as well.

 

[Captainpotatohead]

Do these drugs just not work on some people?

Reason I ask is a friend asked to try some tirz (which they’ve never used before, neither have they used sema) - 1.5mg felt nothing, another 1.5mg felt nothing - they ended up taking 5mg over the course of 2-3 days and eventually had their appetite suppressed but it only lasted 1-2 days before it came back?

 

[Middus]

I mean it literally lists a bunch of cancer that have glp receptors... which is whatever... but he was talking about no logical reason.. which there is.. infact if read your article it talks about 4.3X risk of cancer in a glp in humans.... also says "difficult to know cancer risk" but probably low.. thats the tested ones...so before you think ur gunna have a drop mic moment, perhaps consider what authors say ie they don't know...

just remember usually when start seeing signals of course drug companies pay for studies to say naa...

AGAIN point was simply taking unapproved drug that has plenty of potential to have cancer as a side effect esp since acts on other receptors is unwise...

if have been alive long enough you should know there is no free lunch and side effects and knowledge of even how or why these drugs work often changes...

Big pharma does do great things I agree, but lets be honest there is some shady shit on the best of days...

as great man once said
"to back to reddit-Tracy"

LoL. This is not True!

uh? I literally used what they said in the literature she posted? don't fool yourself, taking approved meds can cause issue never mind UN approved drugs ESP that they are acting on different receptors.

I guess this is a case when people read a tiny amount and ignore the rest AND what the AUTHORS actually said as a conclusion.

hilarious everything people disagree with even with no logic involved is MSM...

"There is a risk for kidney stones, but generally, it's mostly in fightting athletes (they way they train) that cause those problems with the kidney and liver, and it quickly returns to normal."

where do u get this from? "only in fighters"... what about the case studies showing renal failure in people taking ozempic that is permanent? Do you know Drs WONT put you on ozempic if have renal issues form diabetes? So what in your expert opinion causes the issues with kidneys? your saying its NOT from loosing too much weight too fast? than what?

Anyway, just remember me in 10-15 years when more serious side effects show up... there is no free lunch... certainly obese pre diabetic may show benefit as heading to a sooner death... but what about healthy people who just want to loose some weight? maybe there is a reason they need you do be above 30BMi to RX...

but again, my point is even science is not agreed on approved GLP... its a pretty big leap saying Reza is safe even before its even approved.

what's crazy is folks LOVE unapproved meds when it fits their wants. But prob say F big pharma for trumps warp speed vax...

anyhoo, do as u wish, just wanted to point out some flaws in your logic.

Researchers have been toying around this class of drugs for years.
A few "-tides" have fallen by the wayside. In 10-15 years there may be other "tides" e.g IBI-362 and BI 456906 that may make us do away with with sema. There are even newer drugs targeting appetite suppression of those blocking glucose absorption from the GIT.
While I agree with you that you can never be sure about anything, that applies for every single medication we have had in the past 30 years. I wouldn't get too worried about unknown severe long term consequences, especially with a medication people took daily for years.

That it worsens kidney function in people with chronic renal failure is just that. It has been observed in a few people, and because it is a new drug, doctors will err on the side of caution for those groups of patients. I know 2 of such cases were women in their 80s so there might not be too much to garner from that. SEMA itself is shown to improve kidney function by ameliorating conditions that lead to renal failure and also reducing microalbuminuria. So, it helps in the early stage but is worse in the latter stages.

All this tells us to do, is to be vigilant. Long term Ibuprofen use for example increases risk of death for women with endometrial cancer, yet improves rates of survival in those with certain types of lung cancer. What do we make of ibuprofen consumption then?

IF we are concerned about abuse, fine. but the narrative of 'unworthy' use of medication needs to take a backseat. Minoxidil's most popular usage today was a side effect in its clinical trial; same goes for viagra. When studs with a weak one pop blu-chew, do we really scream "that is associated with an 11% risk of melanoma?"

 

[DeltsWanted]

Do these drugs just not work on some people?

Reason I ask is a friend asked to try some tirz (which they’ve never used before, neither have they used sema) - 1.5mg felt nothing, another 1.5mg felt nothing - they ended up taking 5mg over the course of 2-3 days and eventually had their appetite suppressed but it only lasted 1-2 days before it came back?

There are some folks who are non-responders, I found this article that talks about how 9% of users don't even lose 5% of their body weight and how we need to investigate possible genetic factors causing this. Most of the meat of it is Greek to me but maybe some of the smarty-pants around here can make more sense of it. Variation in responses to incretin therapy: Modifiable and non-modifiable factors