In Novo’s Own Words: Degradation of Amylin Analogs Such as Cagrilintide (and How to Test For It)

I literally just shared direct quotes from Novo Nordisk about their own drug. Which of their statements do you consider 💩?
You seem to have a weird fibril fetish and are well known for it in the community. I’m pretty sure others have already tried to talk you down so I won’t waste my breath. I will refer you to my previous comment and cited article.
 
You seem to have a weird fibril fetish and are well known for it in the community. I’m pretty sure others have already tried to talk you down so I won’t waste my breath. I will refer you to my previous comment and cited article.
Who are you to judge people's fetishes, I'm sure you have some too 😶‍🌫️
 
This forum fucking sucks.

And the worst thing of all it's the best GLP1 forum there is.

Fuck.
Hehe, take good informations and just discard the rest, I don't bother sharing anything anymore like a ton of good members here

You gotta think like the rest of them, play along
 
For the chemistry majors here’s research article about amylin and fibrils. For the TL;DR, yes fibrils were a concern which is why modifications have been made to cagri to suppress fibril development. You can scroll to the summary at the end if chemistry isn’t your thing.

I already linked to this article in my original post and heavily quoted from it, as well as several other sister reports from Novo. Clearly you never read my post to begin with if you think your post somehow counters it. 🙃
 
I already linked to this article in my original post and heavily quoted from it, as well as several other sister reports from Novo. Clearly you never read my post to begin with if you think your post somehow counters it. 🙃
I admire your persistence sir/mam
 
If you keep reading you can see that I did, with a cited article. I think qualligator.com will be much more receptive to this post.
You don't need to follow safety advices, nobody is forcing you to, hopefully you'll sleep well anyway 🙏
 
If you keep reading you can see that I did, with a cited article. I think qualligator.com will be much more receptive to this post.
You cited the same article that I already cited first. It's literally the first link on my list of citations.

Except it proves my point, not yours. 🙃
 
I already linked to this article in my original post and heavily quoted from it, as well as several other sister reports from Novo. Clearly you never read my post to begin with if you think your post somehow counters it. 🙃
Then I don’t think you understood the article. What exactly are your concerns? Even if your cagri did have fibrils, they will not cross the blood-brain barrier or enter into your bloodstream. Maybe you’d get an ISR which plenty of people already get with tirz. No human trials to date have shown any amyloid fibrillation formation.
 
You cited the same article that I already cited first. It's literally the first link on my list of citations.

Except it proves my point, not yours. 🙃
You’re right I diid not closely read his lengthy post but I have seen this around elsewhere. The chemistry article does not support his fibril fears IMO.
 
Then I don’t think you understood the article. What exactly are your concerns? Even if your cagri did have fibrils, they will not cross the blood-brain barrier or enter into your bloodstream. Maybe you’d get an ISR which plenty of people already get with tirz. No human trials to date have shown any amyloid fibrillation formation.
You're missing the point he's making, try again
 
Then I don’t think you understood the article. What exactly are your concerns? Even if your cagri did have fibrils, they will not cross the blood-brain barrier or enter into your bloodstream. Maybe you’d get an ISR which plenty of people already get with tirz. No human trials to date have shown any amyloid fibrillation formation.

You should read his post...

“Some of these toxic oligomeric species are associated with beta-cell death and the progression of type 2 diabetes (16−18)”​

Here, they cite research showing that not fibrils, but toxic oligomers are what cause the death of the insulin-producing beta cells in the pancreas. This is from the first study cited:

So while brain is obv concern... He's saying it's possibly hard on your pancreas.
 
Then I don’t think you understood the article. What exactly are your concerns? Even if your cagri did have fibrils, they will not cross the blood-brain barrier or enter into your bloodstream. Maybe you’d get an ISR which plenty of people already get with tirz. No human trials to date have shown any amyloid fibrillation formation.
You are very confused...
 
View attachment 4063

Don't they speak to the different pH levels (4 and 7.5) while subjecting Cagri to mechanical stress?

And they couldn't form any fibrils? Are you saying that this is incorrect and they didn't use the right equipment to test for formation of harmful molecules?
We went over this in the other thread - that is not what this section says. The table with the ThT assay results specifically shows they were able to form fibrils at 7.5
 
For the chemistry majors here’s research article about amylin and fibrils. For the TL;DR, yes fibrils were a concern which is why modifications have been made to cagri to suppress fibril development. You can scroll to the summary at the end if chemistry isn’t your thing.

I don't know if fibrils (or oligomers) are of concern but y'all need to stop sharing this link acting like it says cagrilintide does not form fibrils at 7.5, because the paper explicitly says that it does.

Go to Table 5 and look at analogue 23 - that is cagrilintide - and look at the results for the 7.5 pH. It explicitly fails the metrics they set for the assay to be considered a success.
 
We went over this in the other thread - that is not what this section says. The table with the ThT assay results specifically shows they were able to form fibrils at 7.5

EDIT: Nevermind. I used chatgpt to help sort out this study... Here's what it said...

While the results indicate that Compound 23 did not entirely avoid fibrillation at pH 7.5, it demonstrated delayed onset and moderate recovery, making it less prone to fibrillation than many other analogues. However, this performance still falls short of the study's ideal metrics for fibrillation resistance.

Why Was This Tolerated?​

The study's authors prioritized stability under the intended formulation conditions (pH 4.0), where Compound 23 performed well:

  • At pH 4.0, Compound 23 exhibited a long lag time (45 hours) and high recovery (96%), indicating robust stability in the acidic conditions planned for its use.
  • The lower pH mitigates fibrillation risk during storage and administration, making it clinically acceptable despite its suboptimal performance at pH 7.5.

Conclusion:​

Yes, Compound 23 formed fibrils at pH 7.5, as evidenced by the lag time and reduced peptide recovery in the assay. However, its overall performance across conditions and suitability for acidic formulations justified its selection for clinical development.
 
Last edited:
All but convinced this is megaliths original discord username and megalith was his alt for peptide purposes. Even went back and compared grammar and writing styles.

Last night, I applauded him for his compilation of research and conclusions, but yet he just couldn't stop responding over if we believed the peptide community was "turning" toward accepting the conclusions.

Both he and megalith (if they are even two different people) care more about being seen as the smartest person in the room and attacking others in a derogatory manner than they do about letting the science speak for itself.

No one will ever take either of them seriously because of their approach. Put your ego(s) aside and try to have some discourse. Both of you are way too in your feelings on the topic and it hampers credibility.

Even if I said the conversation didn't need to continue, as we were aligned on the science, but not aligned on the "community" changing their opinion, he still simply couldn't let it go and reiterated a point that had nothing do with what we weren't agreeing on.

The loudest person in the room is never the smartest. If you aren't megalith, maybe learn from his mistakes and try a different approach.
 
Serious question what about mixing a little vinegar ph 2.4 in with the bac and test with a pH strip
 
All but convinced this is megaliths original discord username and megalith was his alt for peptide purposes. Even went back and compared grammar and writing styles.

Last night, I applauded him for his compilation of research and conclusions, but yet he just couldn't stop responding over if we believed the peptide community was "turning" toward accepting the conclusions.

Both he and megalith (if they are even two different people) care more about being seen as the smartest person in the room and attacking others in a derogatory manner than they do about letting the science speak for itself.

No one will ever take either of them seriously because of their approach. Put your ego(s) aside and try to have some discourse. Both of you are way too in your feelings on the topic and it hampers credibility.

Even if I said the conversation didn't need to continue, as we were aligned on the science, but not aligned on the "community" changing their opinion, he still simply couldn't let it go and reiterated a point that had nothing do with what we weren't agreeing on.

The loudest person in the room is never the smartest. If you aren't megalith, maybe learn from his mistakes and try a different approach.
Here's exactly what happened.

I said the tide has been turning of late about this cagrilintide topic.

You denied it.

I suggested maybe you're just not up to date, and I pointed to evidence: multiple people within the chat including the server owner who said they had finally been persuaded by my recent write-up (the same one I posted here).

You mocked my response with a laugh-react (🤣) and then once again denied that the tide was turning, citing the cagrilintide promos that had been selling out as evidence.

My response:
There's a difference between "turning" and "turned" that you seem to be conflating. For cagrilintide promos to stop selling out would indicate it has completely "turned." Whereas pH buffered cagrilintide now being offered is a sign that it's "turning." So yes, it's turning, but still plenty of people behind the curve.

Then you got defensive and accused me of being "condescending" because I said "you seem to be conflating." But you did conflate them, and as I responded:

You set the tone when you laughed at my comments attempting to substantiate the turning of the tide (and it is turning). I don't mind, but don't clutch pearls when I respond in kind.

Then you went back and heavily edited ALL of your previous messages, making them sound more reasonable.

And now, here you are dragging this petty grievance onto another platform, acting like a victim when you started with the mocking and couldn't handle a little "condescension" in return.

The tide *is* turning and you loudly denying it across multiple platforms ain't gonna change that.

And now you say:
No one will ever take either of them seriously because of their approach.
Except you already take me seriously. You praised my write-up repeatedly and described it as "persuasive."

That's one more person publicly aligning themselves with Novo Nordisk, demonstrating the continued turning of the tide. 🌊
 
Last edited:
I can’t speak for everyone, but personally I have no problem with the idea that cagri could have some requirement to be reconstituted at a certain ph for efficacy or safety or both. It’s something that should be discussed.

However, the origin of it (as I gather you’re well aware) was based on a sloppy mess of megalith’s chatgpt theories that didn’t pass muster, and since then the topic has been a magnet for “I am very smart, don’t my farts smell nice?” blowhards. My pushback on OP was not about the content of his community college analytical commentary of some research papers, it was the joining a forum and being a giant asshole in the first post. It was particularly triggering because how on-brand it was for these cagri ph guys.

Let me get this straight.

You reply several times to my post, never addressing any of the actual science in it, but instead repeatedly launching ad hominems, personal insults, conspiracy theories about my "true" identity, and lies of omission to misrepresent me.

But I'm the "giant asshole" here because my first post was a rigorously-researched report with extensive citations about a contentious topic that's being vigorously-debated across multiple platforms including this one.

Got it.
 
Here's exactly what happened.

I said the tide has been turning of late about this cagrilintide topic.

You denied it.

I said maybe you're just not up to date, and I pointed to evidence: multiple people within the chat including the server owner who said they had finally been persuaded by my recent write-up (the same one I posted here).

You mocked my response with a laugh-react (🤣) and then once again denied that the tide was turning, citing the cagrilintide promos that had been selling out as evidence.

My response:


Then you got defensive and accused me of being "condescending" because I said "you seem to be conflating." But you did conflate them, and as I responded:


And now, here you are dragging this petty grievance onto another platform, acting like a victim when you started with the mocking and couldn't handle a little "condescension" in return.

The tide *is* turning and you loudly denying it across multiple platforms ain't gonna change that.

And now you say:

Except you already take me seriously. You praised my write-up repeatedly and described it as "persuasive."

That's one more person publicly aligning themselves with Novo Nordisk, demonstrating the continued turning of the tide. 🌊
Here he goes again. Even after I agreed with him again in the post on it being persuasive. But I had reached the conclusion before your write up. So please don't give yourself to much of a pat on the back.

I told you and stated above I don't think anything is turning in the community. And your diatribe is just even more reason why it won't turn. For fucks sake. 3 people messaging you and you typing up a summary isnt enough to constitute turning in my opinion.

You and megalith both have the emotional intelligence of a 5 year old. Yall care more about being seen as credible than you do just being a contributor. You're doing more harm than good.

Keep being so loud. Or change your approach. Either way, doesnt matter. You dk you, booboo
 
Last edited:
All it takes is a laughing emoji to get both he and megalith in their feelings🤣
 
Here he goes again. Even after I agreed with him again in the post on it being persuasive. But I had reached the conclusion before your write up. So please don't give yourself to much of a pat on the back.

I told you and stated above I don't think anything is turning in the community. And your diatribe is just even more reason why it won't turn. For fucks sake. 3 people messaging you and you typing up a summary isnt enough to constitute turning in my opinion.

You and megalith both have the emotional intelligence of a 5 year old. Yall care more about being seen as credible than you do just being a contributor. You're doing more harm than good
You conveniently omitted the part about vendors now offering pH-buffered cagrilintide, in response to demand from customers.

You were the first to make a market argument (that cagri promos are selling out).

I responded with a market argument.

Both show demand, except mine demonstrates a recent change in market behavior. You can continue to ignore this fact all you want.

Which platform are you going to air your petty grievances on next?

Maybe you are just butthurt about the Hurricanes losing after blowing that early 21-0 lead?
 
All it takes is a laughing emoji to get both he and megalith in their feelings🤣

I am "in my feelings" because I said the following to you?

There's a difference between "turning" and "turned" that you seem to be conflating.

After which you cried about me being condescending? Textbook case of projection.

You were so butthurt that you had to go whine about me being "condescending" on another platform. 🤣
 
I am "in my feelings" because I said the following to you?



After which you cried about me being condescending? Textbook case of projection.

You were so butthurt that you had to go whine about me being "condescending" on another platform. 🤣
Never did i cry about anything. The whole comment on condescending with "ey" at the end of it was to point out how similar you and megalith are. And why I think you're the same person. You can't see that. Haha. Someone can go on the Swiss and see the interaction. You will continue to respond even when the conversation doesnt need to continue. You can't walk away. Too much emotion

Again, the emotional intelligence of a 5 year old. Stick with the science, your interactions with people are lacking and hurts your credibility
 
@secretweapon is obviously just here to argue in a combative fashion, it is what he does on other platforms as well.
Do you lie about people on other platforms too or just this one?

In response to @nccane on that other platform, someone had this to say:
I’m appreciating @secretweapon sharing a lot of this info. He’s never been insulting or arrogant. He cites tons of research and simply replies and posts with a lot of back up.
That's how I conduct myself on other platforms. But when people completely ignore the science and just talk shit like you've done? Don't play innocent and pretend that you didn't provoke it when it comes back to you.
 
Do you lie about people on other platforms too or just this one?

In response to @nccane on that other platform, someone had this to say:

That's how I conduct myself on other platforms. But when people completely ignore the science and just talk shit like you've done? Don't play innocent and pretend that you didn't provoke it when it comes back to you.
Just a reminder or maybe you don't know much this forum yet, but people here don't care about safety.

They're gonna complain if the product they receive is not 99% pure, or is under filled. But they're gonna use 3 months old BAC water punctured a trillion time to reconstitute and use the same vial to draw and inject from every week. Reconstituting in a non sterile environment without swabbing the vials and things like that. Of course no filtration, no usage of any sterile standards cuz we have one life to live they say

People are cheaping out sooooo much on safety but they're gonna complain as soon as they receive a subpart product. It's almost like they think a quality product can replace safety procedure 😂

It's just mind blowing to me, that people think this way here, so of course when you bring anything about safety that'll complicate their stone age reconstitution process, you're not gonna be liked 🤣
 
Last edited:
They'll think they are using more sterile procedure than people working in this field or vendors. For them, it's just totally normal to do it this way, they never died yet so it must be OK right?! Yet, they complain when the product stings or cause ISR 😂
 
Do you lie about people on other platforms too or just this one?

In response to @nccane on that other platform, someone had this to say:

That's how I conduct myself on other platforms. But when people completely ignore the science and just talk shit like you've done? Don't play innocent and pretend that you didn't provoke it when it comes back to you.
Brother, I'm all but admitting I provoked you. All it took was a laughing emoji to do it. The emoji at first was laughing at your approach to having a conversation around what defines the word "turning", but it turned into trolling for me after that.

You think I'm all torn up about this, I'm not. If you truly aren't megalith, please pay attention to his approach and try to understand why the approach doesn't work for advancing discourse on a serious topic. Calling people ignorant and feeling the need to have a rebuttal for the simplest of comments.

Please, keep going. Keep providing little snippets of conversations. I'm not the one trying to convince a community with my research, you are. You then, by default, have a higher standard to be held to than I do when it comes to credibility on the interwebz.

I'm a dumb ass finance guy giving you a hard time...and it just doesn't click for you. The entire thread proves my point on your emotional intelligence and motivations.

The funniest part of all this....is I agree with your research possibly being correct and stated as such to begin with.
 
Last edited:
I just wish I was half as witty at EWB. This may be the funniest thing I've seen on this forum
1000047854.jpg
 
DMs from two different people I've received in the last hour:

No, that's not true. Your accusation that no one is discussing your original post.

I've asked you for citation [5] and I haven't heard back.

I also wanted to discuss the study where Cagri is referenced as Compound 23 and it did form some fibrils after 45 hours mechanical stress while at pH 7.5

 
DMs from two different people I've received in the last hour:
I'm definitely on the more receptive side of the science being discussed here, but this sort of posting isn't going to win people over. The people that are against you will think you can just easily make them up, and people regardless are very rarely persuaded by random quotes of what other people have to say about you.

Everyone arguing against you is doing it based off of reasons that will not be swayed even if a bunch of people were actively posted in your favor publicly in this thread, and it just comes across as weird and defensive to post them yourself.

Just leave the discussion to the science. If people disagree with you, point out, with references, why they're wrong. The rest of this is just you getting baited into other nonsense.
 
EDIT: Nevermind. I used chatgpt to help sort out this study... Here's what it said...

While the results indicate that Compound 23 did not entirely avoid fibrillation at pH 7.5, it demonstrated delayed onset and moderate recovery, making it less prone to fibrillation than many other analogues. However, this performance still falls short of the study's ideal metrics for fibrillation resistance.

Why Was This Tolerated?​

The study's authors prioritized stability under the intended formulation conditions (pH 4.0), where Compound 23 performed well:

  • At pH 4.0, Compound 23 exhibited a long lag time (45 hours) and high recovery (96%), indicating robust stability in the acidic conditions planned for its use.
  • The lower pH mitigates fibrillation risk during storage and administration, making it clinically acceptable despite its suboptimal performance at pH 7.5.

Conclusion:​

Yes, Compound 23 formed fibrils at pH 7.5, as evidenced by the lag time and reduced peptide recovery in the assay. However, its overall performance across conditions and suitability for acidic formulations justified its selection for clinical development.
It's perhaps even more complicated than just the pH level.

The patent discusses testing they did at pH 4 with various buffers - https://patents.google.com/patent/US20230082544A1/en


Go to [0488] and begin reading, particularly through [0540] - we see that even at a 4.0, different buffers have different levels of fibril formation. Benzoate being the worst, glutamate being the best.

If fibrils are a health concern - and I really have no idea on the science here on if they are or aren't - I think we would need confirmation that the pH and buffering agents are both of the "correct" value/type. It looks like even adding too much buffering agent can also increase fibril formation, though this seems to be less of an issue vs. just the "wrong" PH or agent.
 
Last edited:
None of us here are actual experts on any of this, which is unfortunate because people reading these threads are going to take a lot of what is said here to heart and feel some measure of confidence in things just because people who seemed better informed on a subject wrote out a forum message.

Obviously, we're all signing up for taking significantly enhanced risks in buying vials of white powder from china, reconstituting then, and injecting them. No one should be doing any of this if they're not willing to do the calculus there and decide it's within their risk tolerance.

But I also think we should take potential health concerns with what appears to be directly referenceable science backing them seriously and discuss those as best we can with the level of understanding we have, regardless of whether or not some of the people involved in the discussion might drive us up the wall with how they argue.
 
Really wish we'd spend more time focused on what the OP has written and backed up with scientific evidence, rather than the OP himself.

Because this shit is pretty scary, I know we're used to all sorts of peptides of unknown benefit or harm, but here it seems we have a peptide with a likely known harm.
I wish as well. There’s a few on this forum that have a habit of being contentious while ignoring actual issues of discussion. Someone took the time to put helpful material together and then the opening salvo from one individual is to start attacking who he or she is while really adding nothing of substance to the conversation. I feel sad saying this because I’ve always found this forum to be helpful but there’s been lots of degradation in utility over the last few weeks. Can we just stop these personal attacks and get back to useful discussion??
 

Trending Topics

Forum Statistics

Threads
3,310
Posts
54,566
Members
7,155
Latest member
ruben042914
Top Bottom