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smithscel
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This is a thread I thought would be useful, since I see so many questions on the daily - all of them asking what the best 'peptides' are and why.
Almost everything in this thread was information I gathered from the phase 2 clinical trials, as well as other GLP-1/GIP research that I have been looking at
these are some topics of retatrutide I don't often see covered, hence why I am making this - the basic mechanisms are pretty well documented
To be clear, AI was not used for anything in this thread, whatsoever.
It took quite a while. Enjoy
If anyone actually read the whole thing, (inb4 DNRD), please let me know if you liked it, and whether any research on other peptides would be useful
my tags:
@IrishSlayer1483 @manlet69 @ybuyhgui @Dr.D @Dsm
Almost everything in this thread was information I gathered from the phase 2 clinical trials, as well as other GLP-1/GIP research that I have been looking at
these are some topics of retatrutide I don't often see covered, hence why I am making this - the basic mechanisms are pretty well documented
To be clear, AI was not used for anything in this thread, whatsoever.
It took quite a while. Enjoy
Retatrutide is a weight-loss drug developed by Eli Lilly. It is a triple-agonist peptide, so it activates three metabolic receptors at once.
these receptors are the GLP-1 receptor, GIP receptor, and also the glucagon receptor
it was developed for treating obesity and metabolic disease mainly, but also AFAIK a few other related conditions as well.
It is designed to mimic, and enhance, the effects of multiple different gut derived hormones
These hormones are the ones that regulate appetite and metabolism, as well as energy expenditure
these receptors are the GLP-1 receptor, GIP receptor, and also the glucagon receptor
it was developed for treating obesity and metabolic disease mainly, but also AFAIK a few other related conditions as well.
It is designed to mimic, and enhance, the effects of multiple different gut derived hormones
These hormones are the ones that regulate appetite and metabolism, as well as energy expenditure
I would firstly like to note that it has shown some of the strongest fat-loss data ever recorded in humans, making it potentially the best (in my opinion by far the best) GLP-1 agonist on the market.
here are the phase two trials, please give it a read if you are interested
Retatrutide was shown to be amazing and have great efficacy in the phase 2 trial, and it proved that it can give substantial and sustained weight loss across different dose levels
It also proved to, generally, have a very tolerable safety profile
The highest doses they used, which were 8mg and 12mg weekly, gave mean weight loss of 22-24% at 48 weeks.
This may not sound too crazy but it is extremely impressive fat-loss data and shows how great reta can be
here are the phase two trials, please give it a read if you are interested
Retatrutide was shown to be amazing and have great efficacy in the phase 2 trial, and it proved that it can give substantial and sustained weight loss across different dose levels
It also proved to, generally, have a very tolerable safety profile
The highest doses they used, which were 8mg and 12mg weekly, gave mean weight loss of 22-24% at 48 weeks.
This may not sound too crazy but it is extremely impressive fat-loss data and shows how great reta can be
GLP-1 agonism is going to be the main important mechanism in retatrutide, as with the others (Semaglutide, Ozempic, Wegovy)
this part of the drug is what reduces your appetite and slows gastric emptying (measure of the speed at which the stomach moves its contents along the digestive tract)
this is also what improves blood sugar, which I will get into in a little bit if I mention the benefits reta has as an ancillary
GIP agonism is what improves your insulin response, and it also helps with reducing appetite too. It also may improve the nausea you get on GLP-1s alone.
glucagon agonism, which is a very interesting function of retatrutide, is what increases energy expenditure and increases fat oxidation
it also slightly raises your metabolic rate, which is pretty interesting.
Retatrutide is sort of like the equivalent of Ozempic + Mounjaro + a fat-burner at the same time, if that makes sense
this is why, in my opinion, it is the best option for losing weight.
this part of the drug is what reduces your appetite and slows gastric emptying (measure of the speed at which the stomach moves its contents along the digestive tract)
this is also what improves blood sugar, which I will get into in a little bit if I mention the benefits reta has as an ancillary
GIP agonism is what improves your insulin response, and it also helps with reducing appetite too. It also may improve the nausea you get on GLP-1s alone.
glucagon agonism, which is a very interesting function of retatrutide, is what increases energy expenditure and increases fat oxidation
it also slightly raises your metabolic rate, which is pretty interesting.
Retatrutide is sort of like the equivalent of Ozempic + Mounjaro + a fat-burner at the same time, if that makes sense
this is why, in my opinion, it is the best option for losing weight.
the main reason I love this peptide so much is also its great health benefits and how it acts as an ancillary.
I have a lot to say here, so apologies if it is a bit of a long read (will split into 2 parts)
retatrutide causes really amazing improvements in insulin sensitivity, which is partly what makes it such a great ancillary
it lowers your fasting insulin very well - which is useful for anyone using other compounds as well. it also lowers HOMA-IR (if you didn't know, this is just how much insulin your pancreas needs to produce to control your blood sugar levels, which is important)
an additional benefit is that is improves glucose disposal rate and can help reduce hyperinsulinemia.
these make it an amazing ancillary for anyone using hGH.
for any roid users, it is important to talk about the strong reduction in inflammation
GLP-1 and GIP agonism both lower systemic inflammation
it drops CRP super well, which is - if you didn't know - a substance produced by the liver in response to inflammation (and a few other things) in the body
it also is very helpful for your liver enzymes, so roid users could benefit from this
on the topic of liver, I want to mention that reta decreases fatty liver/hepatic health
it reduces ALT/AST and decreases liver fat percentage, and well as improving hepatic insulin sensitivity
this is a very major health benefit because fatty liver is very common in teens and adults who are eating a shit ton of calories
I have a lot to say here, so apologies if it is a bit of a long read (will split into 2 parts)
retatrutide causes really amazing improvements in insulin sensitivity, which is partly what makes it such a great ancillary
it lowers your fasting insulin very well - which is useful for anyone using other compounds as well. it also lowers HOMA-IR (if you didn't know, this is just how much insulin your pancreas needs to produce to control your blood sugar levels, which is important)
an additional benefit is that is improves glucose disposal rate and can help reduce hyperinsulinemia.
these make it an amazing ancillary for anyone using hGH.
for any roid users, it is important to talk about the strong reduction in inflammation
GLP-1 and GIP agonism both lower systemic inflammation
it drops CRP super well, which is - if you didn't know - a substance produced by the liver in response to inflammation (and a few other things) in the body
it also is very helpful for your liver enzymes, so roid users could benefit from this
on the topic of liver, I want to mention that reta decreases fatty liver/hepatic health
it reduces ALT/AST and decreases liver fat percentage, and well as improving hepatic insulin sensitivity
this is a very major health benefit because fatty liver is very common in teens and adults who are eating a shit ton of calories
It has some nice blood pressure benefits, and it also improves endothelial function which is a great addition
it showed that it could lower resting heart rate after around week 24, but all throughout it lowered BP (systolic as well as diastolic)
GLP-1 agonism also helps with nitric oxide signalling and endothelial function like I mentioned before, which helps with vascular health and risk of plaque formation
probably the best health benefit of reta, is how significantly it improves lipids.
after reading the phase 2 results, its very obvious that it massively lowers LDL and non HDL cholestrol as well as triglycerides.
It also increased HDL, which is great
I also want to say that these lipid changes are completely independent of weight loss and just come from glucagon receptor activity and fat mobilization.
it showed that it could lower resting heart rate after around week 24, but all throughout it lowered BP (systolic as well as diastolic)
GLP-1 agonism also helps with nitric oxide signalling and endothelial function like I mentioned before, which helps with vascular health and risk of plaque formation
probably the best health benefit of reta, is how significantly it improves lipids.
after reading the phase 2 results, its very obvious that it massively lowers LDL and non HDL cholestrol as well as triglycerides.
It also increased HDL, which is great
I also want to say that these lipid changes are completely independent of weight loss and just come from glucagon receptor activity and fat mobilization.
one of the amazing effects of retatrutide is not just appetite suppression, but the super strong appetite normalization people experience, which separates it from semaglutide
Unlike semaglutide which just bluntly suppresses appetite (AFAIK), retatrutide is very good at rebalancing reward driven eating, which is something very beneficial for anyone who finds it typically hard to diet.
it also normalises leptin sensitivity and improves satiety signal control (feeling full, makes you feel more full which is good to prevent eating too much)
and reta helps with reducing the urge for emotional and binge type eating urges.
as opposed to semaglutide, this makes it much better for appetite regulation.
Unlike semaglutide which just bluntly suppresses appetite (AFAIK), retatrutide is very good at rebalancing reward driven eating, which is something very beneficial for anyone who finds it typically hard to diet.
it also normalises leptin sensitivity and improves satiety signal control (feeling full, makes you feel more full which is good to prevent eating too much)
and reta helps with reducing the urge for emotional and binge type eating urges.
as opposed to semaglutide, this makes it much better for appetite regulation.
I think it is also good to talk about some of the less talked about bonus mechanisms, I did some extra research for this section and it was actually pretty interesting
obviously this is somewhat do to just weight loss, but by decreasing total body mass and systemic inflammatory cytokines, reta is great at reducing joint stress and lowering markers of cartilage breakdown (and obviously mobility, by getting less fat lol)
This is also good for athletes who have chronic knee or back issues, but bpc157 may be even better (another thread for that?)
reta improves mitochondrial efficiency, which is something I do not really see people talking about too much
this was not covered in the phase 2 trials, but it has been shown in GLP-1/GIP dual agonist research, and tbh it is likely that retatrutide does this even better.
a very cool aspect I found doing research for this segment, in my opinion, are the neuroprotective effects.
glp-1 agonists help to reduce beta-amyloid plaques as well as oxidate stress in neurons (pretty important)
they also help with excitotoxicity, which is good for long term brain health
finally, I wanted to talk briefly about the cardiovascular remodelling potential with retatrutide
it could (I did not find too much on this) help with arterial stiffness and cardiac workload efficiency
obviously this is somewhat do to just weight loss, but by decreasing total body mass and systemic inflammatory cytokines, reta is great at reducing joint stress and lowering markers of cartilage breakdown (and obviously mobility, by getting less fat lol)
This is also good for athletes who have chronic knee or back issues, but bpc157 may be even better (another thread for that?)
reta improves mitochondrial efficiency, which is something I do not really see people talking about too much
this was not covered in the phase 2 trials, but it has been shown in GLP-1/GIP dual agonist research, and tbh it is likely that retatrutide does this even better.
a very cool aspect I found doing research for this segment, in my opinion, are the neuroprotective effects.
glp-1 agonists help to reduce beta-amyloid plaques as well as oxidate stress in neurons (pretty important)
they also help with excitotoxicity, which is good for long term brain health
finally, I wanted to talk briefly about the cardiovascular remodelling potential with retatrutide
it could (I did not find too much on this) help with arterial stiffness and cardiac workload efficiency
If anyone actually read the whole thing, (inb4 DNRD), please let me know if you liked it, and whether any research on other peptides would be useful
my tags:
@IrishSlayer1483 @manlet69 @ybuyhgui @Dr.D @Dsm
