Reconstituting agent for Cagrilintide

[Christine S]

I'm looking for something other that bactrostatic water for Cagrilintide. The agent needs to have a ph of 4. Any suggestions?

 

[ZippityDooDah]

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]

What’s the downside of uhh not having the proper PH and using cagril? I’ve been microdosing it with standard BAC.

 

[nurseratchit]

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]

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.

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]

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]

https://www.reddit.com/r/cagrilintide/comments/1e4o3u3/scared_about_taking_cagri_read_this

 

[meowTime]

https://www.reddit.com/r/cagrilintide/comments/1e4o3u3/scared_about_taking_cagri_read_this

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]

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​

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.

 

[milos]

I found a study, but it is just an overview of the topic;

Redirecting

Does anyone have a link to some actual research to back up these claims about Alzheimer's risk etc?

 

[AnnSolo771]

https://www.reddit.com/r/cagrilintide/comments/1e4o3u3/scared_about_taking_cagri_read_this

Interesting discussion with PhD Pharmaceutical Chemist, Pharma Med Director, among others.... one cut/paste from SME/PhD mentioned above;

• "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.

. Here is an article published in Feb of this year (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10855385/) that goes in to very deep detail. Here is an excerpt:

"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. The peptide also contains two substitutions: Asn14 Glu, which prevents deamination, and Val17 Arg, which increases solubility at physiological pH and forms a helix-stabilizing salt bridge with Glu14. Additionally, the attachment of a C-20 fatty diacid via α-glutamyl spacer increases the duration of action by binding to albumin. A summary of the available studies of cagrilintide treatment in patients with diabesity is presented in Table 2."

and this vid re

Amyloid hypothesis - beta oligomers and plaques​

- https://dnalc.cshl.edu/view/2134-Amyloid-hypothesis-beta-oligomers-and-plaques.html

 

[milos]

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:

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

 

[JohnnyGobbs]

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]

Need someone taking Cagril with an actual chemistry / biomedical background to look into all this and interpret these findings. It’s over my head.

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.