Living with #Lyumjev. Almost a year in review…

Lyumjev. Still the newest insulin available and still the fastest kid on the block. But a year with it hasn’t always been the most straightforward of considerations…

11 months ago I embarked on the Lyumjev Adventure, having sought a private GP to write me a prescription so that I could purchase Lyumjev from a pharmacy, as the NHS in my area had not added it to the formulary. Roll forward 11 months, and little has changed. While Lyumjev is more available for a number of people in the UK, there have, in the 12 months from June 20 to May 21, been prescriptions for only 759 items containing Lyumjev in total. To put that in context, its older, out of patent brother, Humalog, had 398,970 items prescribed. Yes, you read that correctly. there 525 times as many items of Humalog prescribed as Lyumjev. And Lyumjev costs exactly the same on the BNF.

And as this chart from OpenPrescribing.net data shows, the largest proportion of those were in the Derby and Derbyshire CCG.

So not only is the fastest insulin available hardly prescribed anywhere, even where it is prescribed, there’s only really one CCG that stands out. Across London, where of course there’s supposed to be a London Wide Clinical Commissioning Network, as with the Libre, we have to wait for each region to get it on their formulary. South East London hasn’t got it yet, South West does, and North West will apparently never get it because the commissioners there refuse to prescribe any novel insulins as they will in the future be more expensive than biosimilars, and therefore if you live in that area, well, you’re a in a bit of a bind.

What this all highlights is that access to Novel diabetes treatments (not just pumps, CGMs and closed loops) remains variable by postcode and payment authority, in spite of the costs being the same as Humalog. What was it we said about having a single approval for the UK? Surely, if it is o n the BNF, then local politics, and the waste of time and money this entails, should be removed, and it should just be prescriptible. But leaving the intricacies of the UK system aside….

How was living with Lyumjev over the past 11 months?

Firstly, more expensive than I’d have liked, given the lack of access via the NHS. But I can appreciate that even with that, and paying out of pocket for it, it was hugely cheaper than we see in the USA.

From a an end user perspective, however, it’s been more interesting.

u100

There are multiple posts from the second half of 2020 where I found my feet with the insulin. Those can be found here, here and here. I won’t describe those first months as plain sailing. They weren’t and it was not a lot of fun. Once I finally got to somewhere where I could tolerate it, it became easier, but the goal of fully closed loop has been a challenging one, given my issues with the u100 version of the insulin. In a pump it has taken some getting used to, and anecdotally, other people have had similar issues, and after my initial concerns I had six months where I generally used mostly Lyumjev, and occasionally a mix of Lyumjev and Fiasp. While using the u100, I found that I generally need to change sets after two instead of three days, with only occasionally getting a full life out of the set.

The other major observation was that once glucose levels started to rise significantly outside of a normal range, the effectiveness of Lyumjev seemed to drop off, and the requirement to increase dosing to handle highs was much more evident. This may have been due to its make up, but it’s also possible that the different profile may mean that there is less tail insulin, meaning you need to boost the amount you need to drop glucose levels more and sooner. I remain to be convinced on the latter point, and others have also mentioned this reduction of efficacy in using Lyumjev.

u200

After 6 months of u100 Lyumjev, a suggestion was made in one of the closed loop groups that u200 might work more effectively. So a number of us sequestered some. For those who aren’t familiar with u200 insulin, it is twice the level of concentration of insulin molecules per ml, ie 200 iu per ml instead of 100 iu per ml. What’s also significant is that the Lyumjev has the same amount of Treprostinil per ml as the u100, but because you have double the concentration of insulin, you get half as much additive due to the reduction in volume taken. The immediate reaction to this would be that with less accelerant per dose, you might expect it to work less quickly. And similarly, historically concentrated insulins have moved more of the action to the tail of the curve.

My experience with Lyumjev u200 rather broke that set of assumptions. I found it worked better for me than the u100. The action appeared as good if not slightly better. The insulin obviously lasts longer in the pump reservoir becuase you’re using half as much (ideal for a smaller pump with a smaller reservoir) and as there’s less additive per dose, I found that I have had fewer site issues.

Now, here’s the BUT. U200 Lyumjev comes in Kwikpens only. It has not been approved for pumps. oref1 doesn’t work in u200 concentrations. So this is an entirely off label use, adjusting values to half or double what they would normally be with u200. It’s not something for the fainthearted. I have, however, found it to work better for me than the u100 version. I definitely prefer it.

That’s not to say that at high glucose levels, you don’t need more insulin. That still appears to be the case.

Using Lyumjev in a fully closed loop?

One of the key benefits that many of us believed was that Lyumjev would enable the creation of a fully closed loop version of the DIY APS systems. Admittedly, this is insulin only, but that’s better than nothing. It means you may have to do some tricks to achieve the required variation with exercise, but as this has progressed, we’re starting to see some real performance using a combination of Lyumjev and changes to the original oref1 code that is starting to produce some interesting results.

Back at the end of April, TIR was around 85% with TBR (Time below range) at around 3-4%, using early versions of closed loop code.

While that’s not too bad in real world terms, there are probably too many lows in there. Similarly the longer term measures show a 6.1% HbA1c, a PGS of 27.47 and a GVI of 1.47. Again, in the real world these are really impressive results.

But it doesn’t stop there. Work has progressed on using this faster insulin to generate a “better” closed loop. Three days into testing this development and the results are looking even better. This is why we wanted the faster insulins, and why the u200 really helps.

If we look at TBR and TIR here, we can see that the improved algorithm really does seem to be achieving some amazing things. These three days were all high carb days and included extra large Domino’s Pizza, chocolate, cakes, potatoes, etc. This has been left to run of it’s own accord with no manual intervention. It’s really quite an astonishing feat and demonstrates why faster acting insulins are important.

After nearly a year of Living with Lyumjev, we’re starting to get to where I hoped we might.

Truly outstanding results with minimal intervention.

That’s what a closed loop should offer.

Living with Lyumjev? It took some time to get here, but at last it’s a welcome bedfellow.