In the second article in this series looking at ultra-rapid insulin, we talk about Lilly’s new kid on the block:

Ultra-Rapid Lispro (URLi)

Ultra-Rapid Lispro is Lilly’s new formulation of Lispro to counter Novo’s Fiasp. In a similar fashion to Novo, they’ve added excipients to the Lispro formulation in order to speed the absorption. Specifically:

So what we have is a new, injectable insulin that will arrive around three years after Fiasp, using different excipients that in theory speed it up, significantly.

But by how much? Well the clinical trials have proven very interesting.

Clinical Trials data

URLi has been undertaking phase III trials, and the data presented at EASD 2019 was from the injectable trials – the pump trials are currently ongoing. The data? Well, it’s certainly interesting…

The PRonto-T1D trial was a 52-week study of MDI users and threw up some excellent results. But first, the numbers quoted by Lily are, in comparison to Lispro (Humalog):

All this adds up to something significantly faster than previous insulins. But how much?

Referring to the slides from a second presentation, we can see that early absorption is significantly faster than Fiasp:

50% of max concentration was reached in two thirds of the time of Fiasp, while exposure increase in the first 15 minutes versus Fiasp was 1.5 times. Compared to the older analogues, it was obviously significantly faster.

The other finding of note was the tail:

It appears that we now have an insulin that really does have a tail that is all but done after five hours, instead of the 6-8 that all the others have.

It’s also really noticeable how much less insulin there is in the tail after two hours. Okay, it’s not approaching the levels of Afrezza, but this is notably less than there has been in previous formulations of subcutaneous insulin.

Between them, the data from these trials shows something that is potential much more useful for use in a closed loop system. Okay, it’s not clearing at the rate of endogenous insulin, but it is quicker.

What about site reactions?

In the Pronto-T1D study, there were reports of injection site reactions (a number of 2.7% was given) but alongside that was the statement that these were mostly mild and none led to treatment being discontinued. The question on every pumper’s lips is how this translates into the CSII trial.

Will there be significantly more irritation and will it affect the efficacy of the insulin? We’ll have to wait for those outcomes to find out.

Why do you care about this?

It’s those “on and off” numbers. If you’ve ever seen Dana Lewis speak, you’ll have heard her talk about not bolusing for 2 years, using Fiasp with OpenAPS. For those of us who have issues with Fiasp, an alternative is welcome, and this seems to be an alternative.

What’s perhaps even more impressive is that the time this takes to have an effect is notably faster than that of Fiasp. In using OpenAPS/oref1 terms, this means that if you simply eat, the unannounced meal detection and SMB functions will be more effective in managing post prandial glucose levels than they have ever been. The additional speed of onset suggests that even with high carb meals, we may be able to simply eat and not bolus.

With this insulin, it’s possible that there may be a new bar for enabling true closed loop systems that require no meal announcement, and I for one would love to give it a try as soon as it’s available.

That, of course, is the other question. According to press reports, Lilly has submitted to the FDA for approval. I’ve not seen anything about the EMA though.

Suffice to say that right now, I’m excited about the prospects for URLi in closed loops, both DIY and commercial. Right now, the commercial ones won’t be able to update the models for insulin absorption to keep up. DIY however, will be able to. Maybe there won’t be too much irritation at sites, either…

With this update, maybe the dream of never bolusing or counting carbs again, for any food, will at last become a reality for DIYAPS users. And we all can dream…

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