Christine S
New Member
I'm looking for something other that bactrostatic water for Cagrilintide. The agent needs to have a ph of 4. Any suggestions?
Reconstituting agent for Cagrilintide
- Thread starter Christine S
- Start date
Unfortunately the pH of whatever is being used to reconstitute cag is not necessarily going to have the desired effect depending on what buffers may have been used to control pH prior to lyophilization. Best bet is to use BAC, test the pH, and then try to adjust as necessary with acetic acid. Depending on who produced it, it may reconstitute to the proper pH without any problem.
JohnnyGobbs
New Member
What’s the downside of uhh not having the proper PH and using cagril? I’ve been microdosing it with standard BAC.
nurseratchit
GLP-1 Specialist
Probably just local site pain & irritation but could also result in tissue damage. Some drugs will solidify if not within their pH range which would make them ineffective and you could get little hard deposits (granulomas) under the skin. I am not familiar enough with cagri to know if that’s an issue.
Christine S
New Member
I have checked the ph. twice now and it's at 6 after being reconstituted. I have heard that it is still good for about a month, but any longer than that can actually cause health problems?
Christine S
New Member
PREMISE 2: When fibrils are injected SQ, it will find its way all over your body such as your brain tissue. PREMISE 3: The fibrils that are deposited in the brain tissue cause Alzheimer's. In short, the concern was: going from premise 1 to premise 3, if you reconstitute your Cagri at pH above 4, are you putting yourself at high risk for Alzheimer's? This is what I have been researching
Christine S
New Member
The comments in the thread are actually giving me pause. I bought a cheap cagri kit but I didn't realize there's a possibility of the pH making it harmful. Maybe I'll stick to the GLPs
JohnnyGobbs
New Member
I had this exact same concern and question based on the research I did. It was a bunch of complex and abstract stuff and I’m not a chemist so but I arrived with the same question basically about the fibrils. Again I’m not qualified to answer it. Would be pretty crazy though if just 2 PH degree difference would be this crucial to risk Alzheimer’s. Kinda makes the entire drug seem sketchy regardless lol.
I found a study, but it is just an overview of the topic;
Does anyone have a link to some actual research to back up these claims about Alzheimer's risk etc?
Does anyone have a link to some actual research to back up these claims about Alzheimer's risk etc?
AnnSolo771
New Member
Interesting discussion with PhD Pharmaceutical Chemist, Pharma Med Director, among others.... one cut/paste from SME/PhD mentioned above;
and this vid re
- "I read every single one of the papers in full and I have a PhD in pharmaceutical chemistry. This is a nothingburgur. Yes cagrilinitide is more stable at pH 4. But is stable enough at pH 7 for us to use it. Would I want to store it for six months after reconstitution? No. But the biggest risk is that it degrades and loses some efficacy, not that it forms fibrils and is a safety risk."
- ....much more info in the thread with links to Cagri trials/studies. interesting stuff.
and this vid re
Amyloid hypothesis - beta oligomers and plaques
- https://dnalc.cshl.edu/view/2134-Amyloid-hypothesis-beta-oligomers-and-plaques.html
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OK, but is there a specific research/study? I prefer academic, peer-reviewed studies... I'm not saying it's not true, don't get me wrong, I just prefer to read hard scientific evidence. Discussions on reddit or talks/videos from individuals are not exactly the kind of evidence I am looking for. From the study above, what they say is more like: "cagrilintide suppress the development of amyloid fibrils"...
I found actually contrasting studies, for example:
doi.org
EDIT: forgot to mention this review is actually about GLP-1 RAs however
I found actually contrasting studies, for example:
Clinical Evidence for GLP-1 Receptor Agonists in Alzheimer’s Disease: A Systematic Review - IOS Press
Background: Alzheimer’s disease (AD) is the most common cause of dementia. While preclinical studies have shown benefits of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in targeting core AD pathology, clinical studies are limited. Objective:
doi.org
EDIT: forgot to mention this review is actually about GLP-1 RAs however
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JohnnyGobbs
New Member
Need someone taking Cagril with an actual chemistry / biomedical background to look into all this and interpret these findings. It’s over my head.
AnnSolo771
New Member
Agree. I cannot find anything yet other than threads/links in subreds. I woukd think NEJM might have a study or Nature- but would need a research ‘.edu’ email domain to search/review. Google Scholar is a good place to start for search/ journal pubs.
I have access thru university but I cannot find anything that suggests Cagri causes Alzheimers.
Only articles (but about GLP-1 RAs) that prevent it and that Cagri itself prevents the formation of fibrils.
But again, don't get me wrong, I'm open to anything as long as I can see reliable evidence.
AnnSolo771
New Member
Good info re a broad study, quoted above in my post but all info and studies are still so new that there is not a lot of research out there -- yet. Studies are happening now, not concluded.
www.ncbi.nlm.nih.gov
Interesting site re clinical trials, results, status/phases, a scatter chart and more (create a free account to view): https://synapse.patsnap.com/disease/b3defa728b984052bb1a46f2308f0545
Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity - PMC
Diabetes mellitus is a devastating chronic metabolic disease. Since the majority of type 2 diabetes mellitus patients are overweight or obese, a novel term—diabesity—has emerged. The gut–brain axis plays a critical function in maintaining glucose ...
www.ncbi.nlm.nih.gov
- key point 3.2 Cagrilintide/quote: The therapeutic role of cagrilintide is not fully understood due to limited research, and ongoing studies aim to elucidate its potential. Nevertheless, we have tried to summarize the available data about this promising drug.
- key point 3.2 Cagrilintide/quote: There are several differences in the peptide structure of cagrilintide compared to pramlintide. The proline substitutions (Pro25, Pro28, and Pro29) in cagrilintide suppress the development of amyloid fibrils. Furthermore, the Tyr37 Pro substitution boosts efficacy.
- key point, #4 - Conclusion/quote: Overall, the current evidence suggests that both pramlintide and cagrilintide are safe, effective, and promising drugs that successfully reduce body weight in patients with T2DM and consequently regulate glucose homeostasis. We expect that the results of many critical ongoing studies will shed further light on the clinical pharmacology and therapeutic potentials of amylin and its analogs.
from what I have read so far, cagri prevents the formation of the sorts of fibrils that would cause neurodegeneration/AD, but liraglutide is the proving to be the big big show stopper against AD. I am going to keep looking.
Interesting site re clinical trials, results, status/phases, a scatter chart and more (create a free account to view): https://synapse.patsnap.com/disease/b3defa728b984052bb1a46f2308f0545
It’s amazing watching the fear mongering run out of control. It started with a guy who didn’t know how to interpret a study thinking that cagri will go bad in days if you don’t get creative with reconstituting it, and has developed into cagri causing Alzheimer’s. Mind blowing.
AnnSolo771
New Member
Tis. I personally do not put stock in the idea that Cagri causes AD, at all. But people seem concerned. The studies for Cagri aren't all in yet, so once that info is available, it will likely quiet the multitudes. Assuming the phase 2, 3's don't fail ; ). My RS is currently on Cagri + Tirz.
Do you have additional study info? I like reading it!
this study actually saying it is protective, I still don't see from where comes the idea it causes Alzheirmer'sGood info re a broad study, quoted above in my post but all info and studies are still so new that there is not a lot of research out there -- yet. Studies are happening now, not concluded.
Amylin, Another Important Neuroendocrine Hormone for the Treatment of Diabesity - PMC
Diabetes mellitus is a devastating chronic metabolic disease. Since the majority of type 2 diabetes mellitus patients are overweight or obese, a novel term—diabesity—has emerged. The gut–brain axis plays a critical function in maintaining glucose ...
- key point 3.2 Cagrilintide/quote: The therapeutic role of cagrilintide is not fully understood due to limited research, and ongoing studies aim to elucidate its potential. Nevertheless, we have tried to summarize the available data about this promising drug.
- key point 3.2 Cagrilintide/quote: There are several differences in the peptide structure of cagrilintide compared to pramlintide. The proline substitutions (Pro25, Pro28, and Pro29) in cagrilintide suppress the development of amyloid fibrils. Furthermore, the Tyr37 Pro substitution boosts efficacy.
- key point, #4 - Conclusion/quote: Overall, the current evidence suggests that both pramlintide and cagrilintide are safe, effective, and promising drugs that successfully reduce body weight in patients with T2DM and consequently regulate glucose homeostasis. We expect that the results of many critical ongoing studies will shed further light on the clinical pharmacology and therapeutic potentials of amylin and its analogs.
from what I have read so far, cagri prevents the formation of the sorts of fibrils that would cause neurodegeneration/AD, but liraglutide is the proving to be the big big show stopper against AD. I am going to keep looking.
Interesting site re clinical trials, results, status/phases, a scatter chart and more (create a free account to view): https://synapse.patsnap.com/disease/b3defa728b984052bb1a46f2308f0545
And this sentence "The therapeutic role of cagrilintide is not fully understood due to limited research, and ongoing studies aim to elucidate its potential" is a pretty general one that is basically used in almost every other study
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yeah, based on "science from reddit", funny is it?
AnnSolo771
New Member
Thanks for posting!
OK, so what this study is telling us:
"the pancreatic hormone amylin is its high propensity toward the formation of amyloid fibrils"
but
"development of amylin mimetics addresses the propensity of human amylin to form fibrils"
and
"...is known not to be fibrillating"
So for those of you who are still thinking that Cagri is going to give you AD, please read the full text and try to understand correctly what is written there. If not sure, please ask someone who did study in any medical science related field (at least nurse with BNS degree for example).
ImSW1
New Member
No, that's not how it's supposed to work on the interwebs.
OK, so the system is; I post the most outlandish shit I can think of. Super way out there sort of stuff. I don't provide any research of my own either.
Then, people do all the research for me and then spoonfeed it to me like I'm a 5 year old, since I'm only one level above a functioning idiot. Then I disagree with you and argue forever about how your facts are wrong.
Now, please go back and do your research and let me know the outcome, my internet life depends on it! 🤣🤔🤗🙏👍
PS. Yes, the multiple emoji are a requirement. I don't make the rules, I just follow them.
Next you are going to try and tell me the Earth IS NOT FLAT!
lalalalalalalalalalalalalalalalalalalalal I can't hear you 😉 😛 🤣 ...... 👈🤷♂️ You made the rules
ImSW1
New Member
Dammit, you know the system as well. Easy enough, quickly change the subject.
Yeah, but what about the sun's rotation?Checkmate!
😙🫣🤫🗾🌅♟️
This paper does not provide 'proof' that cagri will not form fibrils. The researchers chose the combination of most stable and most efficacious of the various derivatives studied; still, the stability was measured over the course of 45h, which is a bit shorter than we are storing our peps; and there is not solid evidence in this paper that the compound can remain stable over time at higher pH, only that it is initially soluble.
While hysteria over fibrils may be overblown, complete dismissal that there could be risks (which could be increased when not produced, reconstituted, and stored precisely in the manner developed by the original researchers) is a bit flippant for me.
I think this thread has gone too far from the original topic, I admit its partly my fault, but I could not ignore the claims that Cagri gives you AD.
I can only conclude that there is no scientific evidence that Cagri causes AD.
For those people who disagree, my advice is: don't take it
That's it, really simple.
I can only conclude that there is no scientific evidence that Cagri causes AD.
For those people who disagree, my advice is: don't take it
That's it, really simple.
No one has said cagri gives you AD (except maybe some hysterical person on reddit). It doesn't. Could cagri possibly contribute to a process that has been associated with developing AD? Maybe. I agree with you it seems unlikely. And I agree even more that everyone should inform themselves and make the decision that suits them.
JohnnyGobbs
New Member
This is kinda how I interpreted it. It’s borderline sketchy per the PH and fibrils. I don’t love that they’re going out of their way to not reconstitute like we typically do but that’s all I takeaway from it.
AnnSolo771
New Member
Interesting article synthesizing several studies/research articles re what Cagri does/does not do, when and how, or not. FYI & R.
I do just want to point out this isn't exactly an article, but rather a post made in another forum. While this person has a medical background, they have not directly researched (using the actual meaning of the word!) cagri. While the info is helpful, in my opinion there are a lot of unknowns out there and this writeup makes hypotheses sound like facts. So I would just say read it with that in mind!
not sure about the medical background, with this style of writing its not even on a diploma level
and im not even talking about not understanding basic facts which I highlighted here many times and yet some still not understand it
for me this topic was closed already and still someone is coming with these baseless claims, confusing amylin with cagri - two related but different coumpounds
Conflating amylin and cagrilintide is not the issue here. Many peptides can form amyloid fibrils, including cagrilintide and semaglutide, which is for some reason rarely discussed (although it is discussed in the CagriSema patent filing). The issue is whether or not this poses a risk to anyone injecting them, and nothing I've read said this is an open and shut topic, because it is impossible to know precisely how these peptides act in the body post injection.
I was referring to the post by @AnnSolo771, yours response to that is much more rational, sorry for confusion. However there was already posted research which says amylin mimetics (such as cagri) do not form amyloid fibrils...
But I guess there always will be a group of people who think covid vaccine contain chips etc.
Amyloidogenicity of peptides targeting diabetes and obesity
Since the discovery of insulin, a century ago, the repertoire of therapeutic polypeptides targeting diabetes - and now also obesity - have increased s…
www.sciencedirect.com
And I'm vaccinated, tyvm 🙂 This is science, not conspiracy.
you see if we talk science it must be very specific and relevant
if we use the same logic from the article you post, I can say hay fewer OTC medication can cause children becoming drug addicts., because it contain pseudoephedrine which molecule is almost the same as methamphetamine
if we use the same logic from the article you post, I can say hay fewer OTC medication can cause children becoming drug addicts., because it contain pseudoephedrine which molecule is almost the same as methamphetamine
noteablequotable
GLP-1 Specialist
The Reddit post was complex but also pretty clear about why this is a nothin burger:
- NN designed Cagrilinitide such that it does not easily form fibrils
- In order to get Cagrilinitide to form fibrils it was subjected to a great deal of stress. They increased its PH, but also raised it's temp and put it in a centerfuge for 45 hours.
- Fibrils do not teleport, and will not magically end up in your brain.
So, even if you fail to control temp and pH, as long as you avoid putting it in a centerfuge you shouldn't have to worry about fibrils.
There doesn't seem to be much to worry about here because while Cagrilinitide can form fibrils, it takes a lot of deliberate effort to produce that result.
Christine S
New Member
Its not fear mongering, it's called research. If there is a chance that the peptide can degrade in the wrong solution, I would like to know. That is why I am asking here. I am not finding the answers in my research and I know there are a lot of knowledgeable folks in this forum. Am I wrong?
nonyabizznez
GLP-1 Specialist
You weren't being accused of fear mongering. The Reddit thread was... Hopefully that hyper sensitivity stays there 😜
Jailbreak7
GLP-1 Enthusiast
Question specifically about QSC's Cagri - is "plain" bac water enough or does it need any other things added when reconstituting.. not sure if it requires lowering of ph w/ "additives" or no?.. I thought I saw @Qingdao Sigma 's answer somewhere.. but can't find it now that I need that info...
Regular old bac water does the trick
echohunter
New Member
Can syringe filters filter out fibrils (during injection) assuming they do form in cagri?
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LaughingDuck
New Member
From what I read that's to do with Ph levels (if it's even a thing) and not filters. Am I wrong?
The idea would be to filter out any already formed fibrils.
As for whether it would or not... Amyloid fibrils themselves (and presumably amyloid analog fibrils) are significantly smaller than 0.22μm, however, my understanding is they have a tendency to clump together, and these aggregate clumps can reach sizes that the filter would catch.
If you're going to use cagri, it might be prudent to make sure it's at a low PH and then filter after.
echohunter
New Member
I am just wondering if filtering during injection might decrease the risk of fibrils entering the body (assuming fibrils form in cagri in the first place if pH of the solution is not optimal)
noteablequotable
GLP-1 Specialist
You don't need to worry about fibrils unless you plan to also hear up your Cagri and put it in a centrifuge
echohunter
New Member
I am not really worried, I am just thinking it might be a good idea to filter during injection just in case. It doesn’t add that much more work and filters are pretty cheap.
I don't know that us random forumgoers have a solid enough grasp on the science to be making statements this strong.
I've re-read this multiple times since it was first linked here, and I'm less convinced than ever that it provides the evidence of safety that has been claimed. Analogue 23 was the final selection per the paper, and if we look at Table 5 and the ThT Assay, we do see fibril formation for 23 at 41 hours at a 7.5 pH and a significant difference in recovery % vs. the sample formulated at a 4.0 pH. Yes, the test was in a stressed situation, but how does that translate to the manufacturing process in China, whatever happens pre-lyophilization, or when sitting in the fridge for a month after being reconstituted? I don't know, and I don't think anyone on these forums really does, either.
Ultimately, the cagrilintide patent explicitly states that it must be formulated between 3.5 and 4.5 https://patents.google.com/patent/WO2021144476A1/en - this makes it significantly more difficult for NN. Why do they insist on this pH range if it's fine at higher pH?
IMO, the only responsible thing is to inform people of what information we do have and let them figure it out from their own risk tolerance. It might be perfectly safe! There's a lot of people taking it, so I certainly hope it is. But it also might not be.
noteablequotable
GLP-1 Specialist
Respectfully, I feel like you (and others) are conflating issues that have nothing to do with each other and creating heightened risks where they simply don't exist.
Whether or not Cagrilinitide is safe for long term use is completely separate from the issue of fibril formation. There may be 0 practical risk of fibril formation happening, but it could be proven unsafe for other reasons. In that regard we should treat it just like any other unapproved drug.
There is a huge difference between "pH you need to formulate a specific compound" and reconstitution pH. It is very normal that compounds only form at a certain pH, temperature, pressure, concentration, and are then perfectly stable after. Pretty much all of the inorganic substances we interact with on a daily basis operate this way.
It's possible that the Cagrilinitide we buy from grey sources experiences more "stress", but it doesn't matter if that stress isn't comparable to the stress needed for fibril formation - 41 hrs, 98°, in a centrifuge.
