Effect of preservatives on insulin effectivity and site issues

Continuing the discussion from New insurance is sending me back to MDI after 5yrs on Omnipod:

I was amused, in a way, to see a couple of insurance companies last year (when checking plans) that cover Fiasp while covering Humalog (i.e. lispro) but not Novolog (aspart; Fiasp without the nicotinamide).

I’ve been able to use all three interchangeably but currently I prefer a fourth, lispro-aabc, marketed as Lyumjev as it seems faster without me being able to determine whether there is any actual difference from Humalog.

I suspect this is all hoopla and that there is no difference between the insulins themselvs, rather the problems come down to the precise mix in the preservatives (my various insulins seem to use m-cresol). The issue is discussed here:

https://diabetesjournals.org/care/article-abstract/13/1/71/1954/Preservatives-in-Insulin-Preparations-Impair

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Many references here.

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I found @CarlosLuis 's early 2025 response particularly interesting:

See the remainder of the thread for the link to Tandem’s observation. Maybe it’s canula (plastic) dependent but clearly by that argument it would also be preservative dependent. Site reactions maybe the same, but what about the adhesive interaction?

I don’t see Tandem blaming either the plastic (their canula) or the preservative in that link; neither word occurs in the PDF (the closest leading substrings are “representative” and “replacement”). Cannula gets 39 matches but mostly the ones of interest are about the cannula breaking or becoming completely detached, “dislodged”; the others are instructions.

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@jbowler I don’t think it is tubing or cannula but the plastic reservoir bag. I think most pumps use a hard plastic cylinder reservoir except possibly Twiist.

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There is not a single scientific paper or study done in the last 20 plus years noting any reaction or efficacy issue with insulin used or stored in a plastic container. Any study or paper written mentioning an efficacy or crystallization with any pump approved insulins sold today. It is a shame to see this myth continue to be site by so mane and intern causing confusion and stress to pump users. Would be great if those promoting this “reacts with plastic” myth would step up and remove their incorrect and negative impacting comments.

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You have to look in the right place:

https://www.sciencedirect.com/science/article/pii/S0928098724002847

This is probably not relevant but it is entertaining:

Chemical stability of a tube in liquid transport is amazingly well researched and that does include when the transported liquid contains phenols:

Search for both “phenol” and “cresol” (m-Cresol is a phenol).

IMO there is no way that any manufacturer of an insulin pump would not have read the charts; they are widely published. So I’m sort-of agreeing but because I believe manufacturers know what they are doing, not because they haven’t done the research or checked the conslusions.

Not insulin related. Again pushing a false narrative really helps no one. Look for specific studies that demonstrate an issue with pump approved insulins and plastic.

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The @Sjwprod discussion is continued in the original thread, here:

That thread is important input but there are a lot of issues and this is a core issue for pump users. Hum; I should have been more clear, MDI has site issues and loss of efficacy issues too. I was primarily targeting issues for pump users with regard to the specific formulation of the insulin, the additives (the “salts”, the preservatives) as opposed to the biochemical formula of the insulin itself. That said, all input is welcome; this is FUD.

The effect pf different plasticizes on insulin stability has been documented/published. It is why insulin is sold in glass vials. Both MM and Tandem have long wear sets.

Insulin tends to aggregate into hex-amers that takes longer to dissociate and work; faster acting insulin uses amino acids and a zinc binding site to prevent aggregation. The different engineered insulin’s require different buffers (salts) to preserve the monomers. There is no “preservative” in the insulin. A buffer for one type of insulin may not work for another. Standard tubing (plasticizes) can cause the monomers to break down and form aggregates, and cause inflammation with slower release of the insulin.

Mike

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I don’t think anyone raised plasticisers although that’s a valid issue as they are added to plastics (particularly PVC), however I think that requires some links. Are you mixing up phalates and phenols? Or are phenols used as plasticisers? (I don’t know; links always help.)

The stability of insulin is why m-cresol (IUPAC 3-methylphenol) is added as a preservative. I hadn’t realised that before; thanks for the clue! Here’s a link:

Interesting…

So what do you think is happening in the vial (of insulin)? Is there zinc in there? I’m talking about lispro and aspart primarily but I’m also interested in what you think about novolin/humalin where I assume the stable hexamer forms in the aqueous solution in a vial but that’s just an assumption based on the comment about glusine (“apidra”).

There is so much bad info and irrelevant associations with amateur chemist guessing about interaction that have been studied for decades and demonstrated that the Plastic impact on insulin efficacy has not been demonstrated with the current pump approved insulins.

I wish the admin on this site would get this to stop, it helps no one.

Is you have not been directly involved in studying and manufacturing insulin stop creating doubt and false perceptions about insulin efficacy before you cause harm to others.

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I had previously posted on this topic and gave a link. Here is a link to a YT presentation on this topic. The technology mentioned in this video has been licensed by Tandem.

Insulin is a double chain pleated peptide, and zinc is binds the peptides together. Zinc may be a component of the buffers. There are reviews on pubmed you can read on the biochemistry and pharmacology of insulin(s).

{There is so much bad info and irrelevant associations with amateur chemist guessing about interaction that have been studied for decades and demonstrated that the Plastic impact on insulin efficacy has not been demonstrated with the current pump approved insulins.}

I am not a chemist, and a chemist would not study this topic. It is studied by biochemist and pharmacologist. But, you can do your own literature research and post links substantiating your claim.

Mike

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There is no link here.

I did look up your activity from the past year but could not find a post with a link. Possibly I missed it?

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Is the research done in the early 2000s that led to the development of the Minimed 7 day infusion set? This sounds much like the studies done with pre human insulins. I cannot fine studies showing this in me searches other than those with older insulins.

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Not one of the studies posted in comments site insulin, and are noting testing done with IV tubing and drugs delivered for IV. Why do we keep seeing this faulse connecting to insulins.

A@Sjwprod How about giving us the reason that Tandem recommends in the T:Slim pump which uses a collapsable plastic bag reservoir that Humalog (Lispro) be changed every 48 hours while Novolog (Aspart) every 72 hours.

I am sure this is the result of FDA testing, but I cannot find the reports.

My anecdotal experience is that Lispro is less effective and more prone to occlusions 48 to 72 hours than Aspart.

Why would I use one over the other - ask my Pharmacy Benefit Manager, And they only want 72 hour set change.

To my knowledge no other pump, including Tandem Mobi has the 48 hour recommended site and cartridge change for Humalog (Aspart). The major difference between T:Slim and other pumps is the reservoir.

The Twiist pump uses a collapsable bladder type reservoir but does not have the 48 hour limit as T:Slim. Perhaps this is a different polymer.

Anyway can you help me out here in understanding what causes Lispro to begin degrading in a T:Slim pump after 48 hours while not in other pumps?

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I thought I pasted the link: https://www.youtube.com/watch?v=0HbYIIdqYJ4&t=46s

by Mark Estes of Capillary Biomedical to discuss infusion set technology and tissue response. This discussion was recorded on July 29, 2020.

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@Mikey417 I’ve posted that video in other threads. I think it gives a really good insight of the problem with infusing insulin long term. I think the multiple phase solutions of angled cannula, spiral reinforcement, multiple ports and the tubing and cannula material is spot on.

I think the early part of the video where he discusses the problems and the tissue slides showin the progression of the body’s reaction to the foreign invaders- cannula and exogenous insulin is something that all pump users good benefit from seeing.

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This is because the clinical testing was done with those insulins, not due to issues. Lyumjev is also approved for use with the T:Dlim. You won’t find studies or papers on this because it’s not an issue.

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This is about the subconscious tissue being impacted by the insulin not plastic. The 7 day infusion site is 7 days with the same pump cartridge and insulins. The manufacturers have me approved the insulin is the cartridge for Novolog for 6 days and Lyumjev for 9.

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