May 7, 2019
While insulin affordability and access have been headlining and causing great stress for many, there’s another insulin discussion gaining traction in the diabetes community. Novo Nordisk’s Fiasp®, an ultra fast insulin, may be presenting issues, mostly for people who use insulin pumps. Problems include skin or tissue irritation (inflammation at the infusion or injection site), resistance, little to no efficacy resulting in hyperglycaemia, and pain at site. Fiasp® retails for $685.77 US for 5 flextouch pens (3ml) of 100 units/ml.
Many people have decided the faster action isn’t worth the trouble. Some have given up altogether, dropping the faster insulin to return to their regular fast-acting analogue. Does Fiasp® have flaws causing people who use insulin pump therapy to drop off?
What’s an extra-fast insulin?
Fiasp® (faster insulin) is approved for subcutaneous or IV injection use, although there is little data available regarding its clinical utility in insulin pumps. This is unlike well-known fast-acting insulin analogues Humalog® (lispro), NovoLog® (aspart) and Apidra® (glulisin) which have been used in pumps for decades. These analogues offer coverage of mealtime excursions, but need to be injected (bolus) 10-20 minutes before a meal. This can be a problem if people inject during a meal or even after, which leads to hyperglycemia.
Faster insulin has two extra excipients, L-arginine and niacinamide (Vitamine B3), two natural agents approved by the European Medicines Agency and the US Food and Drug Administration. These agents facilitate the rapid movement of insulin through the capillaries into the blood. Faster insulin aspart covers glucose excursions much better. This leads to improved glucose results.
What did the original insulin pump trial study find?
In a 2017 study, 37 adults ( ≥ 18) were randomized in a 2:1 ratio of faster aspart: insulin aspart for 6 weeks of treatment using insulin pump therapy. Participants were instructed to change their pump sites every 72 (±4) hours. If there was any suspicion of occlusion or blockage, leakage, unexplained hyperglycemia, infusion-site reaction, or other technical reason, participants were instructed to report and change their site.
Overall, there were 21 premature infusion-set changes reported by 11 (44%) subjects in the faster aspart group and four premature changes reported by two (16.7%) subjects in the insulin aspart group. In the faster aspart group, six changes were prompted by unexplained hyperglycemia: only one experienced a blood glucose >300 mg/dl.
That research determined over the 6 weeks of treatment “no microscopically confirmed infusion-set occlusions were observed for faster aspart or insulin aspart indicating similar compatibility” for insulin pump therapy. The authors concluded “faster aspart demonstrated a nonsignificant trend toward improved glycemic control with no new safety issues.”
DiabettechMay 7, 2019 at 3:17 pm
I think the headline is a little misleading, as there’s really only Fiasp available right now. Are faster insulins worth it? Definitely, but not flawed ones. The chemistry of Fiasp appears to be at fault though. Lilly apparently have something in the works that uses a vaso-dilator, and there has been the ongoing “Bio-Chaperoning” model that Adocia were working with Lilly on. Both of these looked very promising, but we’ve not seen much movement in public on them. I’d suspect that they’ve quietly gone away and looked at the issues that have been highlighted with Fiasp and checked to see if they apply with their solutions.
With regard to Fiasp in pumps, Novo released the ONSET-5 study results very quietly in July 2018, with 236 participants using Fiasp in pumps and 236 using Novorapid/Novolog. I summarised it here: https://www.diabettech.com/insulin/fiasp-and-the-onset5-csii-trial-what-novo-nordisk-found/
I’ve not seen any papers written about it (unusually) and I assume this is because the results were not spectacularly superior. As it was configured as a non-inferiority trial, the Fiasp was shown to be statistically non-inferior, but the absolute numbers on the primary outcome (change in Hba1C) were slightly worse.
In addition, there were more adverse events linked to infusion sites and irregular set changes.
Obviously it’s dangerous to draw conclusions, but it’s the only full study that’s been done in a clinically controlled, double blind setting, and the outcomes seem to raise the same questions the EMA approval study did, just in a larger user group.