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

[nccane]

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

 

[nccane]

All it takes is a laughing emoji to get both he and megalith in their feelings

 

[secretweapon]

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?

 

[secretweapon]

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.

 

[nccane]

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

 

[peptideusername]

Good lord this is painful.

 

[exploitedworkerbee]

@secretweapon is obviously just here to argue in a combative fashion, it is what he does on other platforms as well. I'll permit it in this thread only. Have at it, don't spread to other threads.

 

[secretweapon]

@secretweapon is obviously just here to argue in a combative fashion, it is what he does on other platforms as well. I'll permit it in this thread only. Have at it, don't spread to other threads.

No, I'm here to talk science. Are you?

 

[secretweapon]

@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.

 

[secretweapon]

DMs from two different people I've received in the last hour:

Nobody is discussing the material in your post. Odd.

You're being gaslit over there, it's not all in your head lol

 

[scarywood75]

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

 

[scarywood75]

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

 

[nccane]

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.

 

[nccane]

I just wish I was half as witty at EWB. This may be the funniest thing I've seen on this forum

 

[brentm]

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

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

Dec 1, 2024

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...​

• brentm

• 

 

[hexagonal]

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.

 

[hexagonal]

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.

 

[hexagonal]

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.

 

[Peptidase]

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??

 

[clayd]

I care less than zero about who the poster is and the personal background.
I care about whether cagri is safe
Happy to listen to all perspectives