Enough is enough. I can’t go on…. Details of the EMA Submission Fiasp CSII study

Enough is enough. I can’t go on…. Details of the EMA Submission Fiasp CSII study
Enough is enough. I can’t go on…. Details of the EMA Submission Fiasp CSII study

Harking back to a disco classic, I have to put my hands up and admit that I’ve reached the end of my tether with Fiasp after nine months, even after mixing it, both in an F50N (50% Fiasp/Novorapid) and an F40N (40% Fiasp, 60% Novorapid) formulation.

The angry red pump sites came back and the inability to lower blood glucose levels also returned. So instead I returned to my old buddy Novorapid.

And almost instantly it proved to make the difference I had observed when using it in September. I’d like to call it “Old Reliable” as, with appropriate “Eating Soon” and pre-bolusing, those annoying post-prandial climbs that just wouldn’t reduce seem to have gone away.

As an aside, what I’ve also found is that if I carry a small syringe of Fiasp, I can use that effectively via injection to counter a postprandial rise when eating something that is perhaps higher in fast carbs and unplanned compared with the necessary preparation for Novorapid.

Whilst I know that not all Fiasp users have been affected, it feels like a significant minority.

Discussing these effects in various groups on Social Media, there’ve been a fair number of people express similar issues. So it’s interesting to see that someone has finally published an additional paper on the use of Fiasp in pumps, to enhance the limited information available from the EMA submission.

In an article entitled “Pump Users Clamor for Faster Insulin: Is Fast-Acting Insulin Aspart Ready for Them?“, there is discussion of the small scale study undertaken by Zijlstra for the EMA approval that has results that raise similar questions to those raised in social media.

As I and others have mentioned, there was limited Pump Compatibility testing in the EMA submission and this article goes into further details of what was published within that.

What the results highlight, however, is that there are other issues arising.

To cut a long story short, this was a small study with 37 participants randomized 2:1 Fiasp:Novorapid and lasted only six weeks, with a primary endpoint of the number of microscopically confirmed infusion set occlusions during the 6 weeks of treatment. This turned out to be zero in all cases. What makes this odder is that seven expected occlusion events were reported, all for Fiasp, none of which were proved to be occlusion related.

Another endpoint was frequency of premature set changes, and once again, there were a total of 21 premature set changes in 44% of the Fiasp users, compared to a total of four in 17% of Novorapid users. Taking this a step further, one third of those in the Fiasp users group could be attributed to technical issues, where as three quarters in the Novorapid users had the same origin.

So if we weight for number of users in each part of the study, we can see that:

  • The Fiasp group experienced 700% of the premature set changes that Novorapid users saw. There were two premature set changes per 25 users in the Novorapid group versus 14 per 25 in the Fiasp group, none of which could be explained on a technical or occlusion basis
  • 40% of Fiasp users suffered unexplained hyperglycaemia as opposed to 25% of the Novorapid users. Of those, six were unexplained, and seven were thought to be occlusion related, which was later disproved.

For me though, the telling aspect of this is the following statement from the conclusions drawn (the emboldened text done for emphasis):

Pump users should be advised that FIASP may result in the need for additional premature infusion set changes and that more episodes of unexplained hyperglycemia may be expected and should be scrupulously evaluated.

As in everything else in life, risks and benefits need to be balanced, and the likely treatment benefits of FIASP should be weighed against these  potential downsides for pump users. When definitive large-scale pump study results  are available then these recommendations can be revisited.

Nowhere in the package insert do these points get mentioned, and while the EMA released Fiasp with “Enhanced Observation”, there was no mention of what needed to be observed.

This raises an interesting question. If you know, as the manufacturer, that a product you are about to release has characteristics that are potentially unusual, or may be counter to what the product is supposed to do, do you have a duty of care to publish this information? If you don’t publish it, how do users and healthcare professionals know that there was a recommendation to scrupulously evaluate issues?

Would I have changed my decision to use Fiasp if I’d known this? No. Would it have been better to understand that there have been unexplained hyperglycaemic events during testing and further investigation of them was needed? Yes.

As has been discussed in a number of other places, it looks a little as though the use of Fiasp in pumps is much more a Beta release than with MDI. It was a Beta that I happily participated in, but as with any Beta, easy access to the release notes and questions as to what to look out for, plus an easy, direct route for feedback is preferable.

What remains to be seen is what longer term effects are observed in longer, larger pump studies. Will they back up those seen in the vanguard of users or will we get a different story? Whichever it is, I don’t want to see pharma companies stop producing new products or releasing them to us as vanguard users. We want to try them out and want to give our feedback. Just please be more open about what the real risks may be!


Footnote: If you’re a Fiasp user, and especially if you’ve seen similar, I’m trying to collect together user experiences so that they can be shared with those who are interested. You can find the submission form here. The responses so far can be found by following this link.

8 Comments

  1. After 7 months on Fiasp I’m thinking about reverting back to NovoRapid following an unexpected hyperglycaemic few days over the New Year plus more occlusions than normal in December. Was hoping the highs were due to badly placed cannula, a cold, the usual suspects I’m not so sure. Fiasp doesn’t seem to reduce the highs until hours later in the night resulting in a bad night hypo. The lack of predictability ( as much as a type 1 can ever have) is making my life quite hard.

  2. Thank you. Really appreciate the fact that you’ve published all your findings on using Fiasp. Initially, I was really keen to start using it in my pump but held off while I read your reports. Even before this article, I’d decided not to try it in my pump and my DSN suggested using Fiasp, as you have outlined above, as a back up for averting post prandial spikes.
    The problem I have found with this is that I cannot find disposable syringes with short enough needles. The shortest seems to be 8mm whereas when I was on MDI I was using 4mm needles. If you have found syringes with shortish needles, please would you post what they are? Many thanks.

  3. Thanks for all your very helpful information about using Fiasp! Given problem reports when used in pumps, I decided to experiment with it, but using it only for pre-meal injections with a FlexTouch pen; I am still using Novolog in my pump for basal rates. Most unexpected result so far has been post-breakfast hyperglycemia, so it seems the quick onset using a pen isn’t so quick or the insulin sensitivity factor is different . . . I was hoping pump/pen use would avoid problems you experienced and others elsewhere have described.

    • I strongly suspect that the addition of Nicotinamide, whilst speeding up the action of the insulin, also increase the user’s insulin resistance. I’m just not sure whether that’s topical or systemic, and the results that different people have had with it don’t make that all that could suggest either.

      Either way, when I use 100% Fiasp, my carb ratios do change quite a bit on a day by day basis, in a way that they don’t seem to on Humalog.

      • Day 3 for me on Fiasp. To compensate for a “dawn effect” that may be different with Fiasp, I increased basal rate between 4am and 9am from .85/hour to 1.0/hour. Breakfast started about 8:30am with 2 cups of coffee and 1 unit Novolog by pump, followed 45 minutes later by about 42g of carbs (oatmeal, yogurt) consumed 15 minutes after dosing 6 units of Fiasp, An hour later CGM showed a peak of 161 and went down from there.

        So far, the “fast” action of Fiasp is subjectively only slightly better than Novolog by injection, but faster than pump bolus action for decreasing hyperglycemia. The duration is shorter.

        Re nicotinamide levels, shouldn’t a water-soluble vitamin dissipate when using multiple sites for pen injection?

Leave a Reply to Reijo Ahola Cancel reply

Your email address will not be published.


*