Three-way split Levemir?

[Daibell]

I'm on Basal/Bolus and have overall poor control despite Libre 2, low-carb diet and being slim with low body fat. My evening Bolus/Carb ratio is 3x my morning ratio. I have started splitting my Levemir 3 ways with an afternoon injection to try to control my evening BS curve. Does anyone else do a three-way split? Injecting a lot more Bolus in the evening has little effect on my BS.

 

[Jaylee]

I'm on Basal/Bolus and have overall poor control despite Libre 2, low-carb diet and being slim with low body fat. My evening Bolus/Carb ratio is 3x my morning ratio. I have started splitting my Levemir 3 ways with an afternoon injection to try to control my evening BS curve. Does anyone else do a three-way split? Injecting a lot more Bolus in the evening has little effect on my BS.

Hi,

To be quite frank. All the Libre does is sketch in twix the meter tests?
It is how the insulin regime works for you that does the job.

How is the 3 way split working for you? Had you done any basal testing prior to your change to your new dosing. https://www.mysugr.com/en/blog/basal-rate-testing/

 

[Daibell]

Hi,

To be quite frank. All the Libre does is sketch in twix the meter tests?
It is how the insulin regime works for you that does the job.

How is the 3 way split working for you? Had you done any basal testing prior to your change to your new dosing. https://www.mysugr.com/en/blog/basal-rate-testing/

Yes, I've done Basal testing from time to time to get my balance as good as I can. I use my Libre graphs to see how my BS is trending. My large ratio variation from morning to evening appears very unusual. Yes the third afternoon Basal does help.

 

[Jaylee]

Yes, I've done Basal testing from time to time to get my balance as good as I can. I use my Libre graphs to see how my BS is trending. My large ratio variation from morning to evening appears very unusual. Yes the third afternoon Basal does help.

It would be great to hear from other basal 3 way splitters.
Oddly, (we appear to be the same sort of build, body image wise.)
But my insulin sensitivity improves the latter half of the day. To the point (pending on evening activity.) I can delay my basal long after it should have worn off.. I also do Lantus. Which is a conundrum on a daily basis, in itself..

Hers hoping to bump this topic for you & have some input from Levemir splitters.

Just a quick one regarding your Libre. (You know this.) Are you checking against your meter that everything trending is reasonably calibrated? It’s easy to rely totally on the sensor during a hectic day..

 

[jaimet]

I'm late to the party but yup, I'm another 3-way levemir splitter. I've tried taking it only twice per day, but it runs out well before I'm due to inject again.

As I'm new here, I can't post links yet, but there is an interesting post on straighthealthcare dot com (the insulin chart page) that says that for a dose of 0.1 units/Kg (that's more than my usual dose!), the duration of levemir is only 6 hours.

There's another interesting 3D graph on the fudiabetes forum thread entitled "Dose once or two times a day with tresiba?", post 47/76, entitled "Levemir: typical profiles according to dose." I haven't been able to find the source of that image.

Finally, the document "Basal Testing with Multiple Daily Injections" on the diaVerge website also says (on page 3/3) to split Levemir 3 ways.

All interesting stuff, but it may be only temporary - Levemir is being discontinued in the USA this year, as I am sure you all know. HTH.

Edited to add links (now that I can):
The "insulin chart" page on straighthealthcare dot com
The 3D graph on tudiabetes.org (not fudiabetes.org) entitled "Levemir - typical profiles according to dose". Previously, I had not be able to find the source of this graph but now that I look at the plot lines, it looks remarkably like the data from "Plank et al" (2005) (see later posts for more info).
diaVerge's "Basal Testing with Multiple Daily Injections."

 

[SimonP78]

It's interesting that there's a difference in duration based on the quantity of insulin injected - I've wondered about this in passing. I wonder if it's that there's a minimum concentration required to have an effect (i.e. glucose removal from the blood stream is non-linear with insulin concentration, which is probably quite likely), or if there's a fixed rate at which insulin is broken down (such that low concentrations are broken down more quickly, so the tail is cut short, which is probably also quite likely.)

I don't have anything to add to the 3-way split discussion I'm afraid, but am interested to know if the reason you do this is because you find it doesn't last as long as expected (Levemir is nominally a 24h insulin so I understand), or if it's to try to tune how much is active at different times of the day?

 

[jaimet]

but am interested to know if the reason you do this is because you find it doesn't last as long as expected (Levemir is nominally a 24h insulin so I understand), or if it's to try to tune how much is active at different times of the day?

Since my last post, I discovered the source of the straighthealthcare dot com info. In the May 2005 edition of "Diabetes Care", "Plank et al" published their report "A double-blind, randomized, dose-response study investigating the pharmacodynamic and pharmacokinetic properties of the Long-Acting Insulin Analog Detemir". I can summarise this report as follows:

Dose	(Example dose for 85 Kg adult)	Onset (hours after injection)	End (hours after injection)	Duration (hours)
0.1 u/Kg	8.5u	2.0	7.6	5.6
0.2 u/Kg	17.0u	2.0	14.0	12.0
0.4 u/Kg	34.0u	1.6	21.5	19.9
0.8 u/Kg	68.0u	1.1	23.7	22.6
1.6 u/Kg	136.0u	0.8	23.9	23.1

I'm quite insulin-sensitive - the maximum levemir/detemir dose that I can tolerate is ~ 7 units. Hence I use the first row in the table, hence my levemir/detemir "kicks in" after 2.0 hours and finishes 5.6 hours later (7.6 hours after I injected.)

You say "Levemir is nominally a 24h insulin". Well, yes it is, provided that you are injecting enough. I can only tolerate a maximum of 0.1u/Kg, however, so for me, Levemir is not a 24h insulin.

In case any else reads this post, it's worth nothing that these values were derived using "a randomised, double-blind, cross-over, placebo-controlled glucose clamp study" i.e. using hyperinsulinemic - euglycemic glucose clamping.

In case you're interested in the report, it's PMID (PubMed ID): 15855574 and the pdf is freely available. It's quite dense, but it's only 6 pages long. HTH.

Edited to add the following link to the report:
Plank et al, 2005

 

[SimonP78]

Sorry, my "nominal" was simply because that is what is often quoted. I've certainly read a similar paper/report so don't doubt that it is a problem, and I will have a read of the paper you've linked.

I'm interested to understand what the mechanism is and am surprised that there's not more information available about basal insulins and tuning them - I split my abasaglar, and when I started doing this was very surprised to find that no tools exist to tune timings and quantities to match a given background requirement.

My interest was/is in splitting dose to generate quite significantly different levels of active insulin across a given 24h period - on the one hand to have less active while doing some cycling, and on the other to have less active overnight after said cycling to avoid hypos. I didn't ever look at dose-related effectiveness and duration as I had to do the modelling and make a decision quickly (the ride was a couple of day off), but it was and still is on my todo list to include it (along with implementing the whole thing in e.g. Excel or Google Sheets rather than MATLAB, to make it accessible.)

Thanks for the info

 

[Antje77]

Since my last post, I discovered the source of the straighthealthcare dot com info.

Once you've posted 5 posts you'll be able to add links to your posts.
Since you qoute so many interesting sources it might be worth posting a couple more posts so you can add in the links.

 

[jaimet]

Once you've posted 5 posts you'll be able to add links to your posts.
Since you qoute so many interesting sources it might be worth posting a couple more posts so you can add in the links.

Don't worry - I'll keep posting!!

 

[jaimet]

Once you've posted 5 posts you'll be able to add links to your posts.
Since you qoute so many interesting sources it might be worth posting a couple more posts so you can add in the links.

And if I add this post, then I should be able to include links in my next post perhaps....

 

[Antje77]

And if I add this post, then I should be able to include links in my next post perhaps....

Just one more...

 

[jaimet]

Just one more...

I thought 4 would be enough, so I wrote a long reply with links, but the system didn't accept it! Hah hah! Time to try again...

 

[jaimet]

Ok, here goes.

<rant on>
Here's the "Straight Healthcare" page that contains the table that piqued my interest. And here is the "Plank et al" (2005) report that I managed to trace it back to. I've spent close to 12 years trying to convince every endocrinologist that I've ever met at the hospital to let me split my basal 3 ways rather than 2 (i.e. every 8 hours rather than every 12 hours) and at every appointment, I get the same "Can you please just take your basal twice per day." I now have something scientific that says I'm right. If I had a penny for every hour I've wasted trying to prove my point, I'd be a rich man.
<rant off>

 

[Antje77]

Ok, here goes.

<rant on>
Here's the "Straight Healthcare" page that contains the table that piqued my interest. And here is the "Plank et al" (2005) report that I managed to trace it back to. I've spent close to 12 years trying to convince every endocrinologist that I've ever met at ***** ******* Hospital to let me split my basal 3 ways rather than 2 (i.e. every 8 hours rather than every 12 hours) and at every appointment, I get the same "Can you please just take your basal twice per day." I now have something scientific that says I'm right. If I had a penny for every hour I've wasted trying to prove my point, I'd be a rich man.
<rant off>

I went with the short version, considering the time of day, very interesting!
I don't understand your endo's, why would they mind you using an extra injection?

I'm very lucky with mine, who is mainly curious about my thoughts and experiments.
Can't say if the time of action is correct for me, according to your information, but I don't use Levemir as my main basal, only as a top up of Tresiba. This gives me the steadiness and large leeway with dosing times of Tresiba, which I love, plus the adjustability of Levemir on a daily base of Levemir, which I also love.
In real life this means 98 units of Tresiba for the last couple of years (except for last month, something funny is going on which is irrelevant on this thread), and anywhere from 0 to 25 units of Levemir, mostly only before bed, sometimes split morning and night. I weigh 114 kg.

My endo didn't expect the Levemir to be a useful addition at all, but she was happy to prescribe if I wanted to try because why not. Turned out to be very useful!
Same with metformin when I wanted to try (didn't do much, nice experiment though), and when Lyumjev had just been approved and I asked for a script for a couple of pens to see how it worked, she's happy to support me in my thinking.

Should Levemir be discontinued in Europe as well, I expect I can pull the same trick with NPH, which might even work better for my purposes.

(As an aside, you might want to remove the name of the hospital, naming HCP's is not allowed on the forum. Not sure if this extends to hospitals but it'll save the mod team some work if it's not there. I edited your quote to asterisk the name.)

 

[jaimet]

(As an aside, you might want to remove the name of the hospital, naming HCP's is not allowed on the forum. Not sure if this extends to hospitals but it'll save the mod team some work if it's not there. I edited your quote to asterisk the name.)

Done - thank you for the hint. My anger got the better of me. (And yes, I'm still very angry.)

 

[jaimet]

I don't understand your endo's, why would they mind you using an extra injection?

Because they think that levemir / detemir has an invariable (non-dose-dependent) duration of 24 hours.

 

[Antje77]

Because they think that levemir / detemir has an invariable (non-dose-dependent) duration of 24 hours.

But even if this would have been correct, you're happier taking it 3 times a day so taking it 3 times improves your quality of life. Which is the goal. It doesn't hurt them in anyway, why would they mind?

I can imagine you're angry with them. Even Novonordisks own information sheet on Levemir tells the action profile depends on the dose and twice a day administration may be necessary. (https://www.novonordisk.co.nz/content/dam/nncorp/nz/en/pdfs/datasheets/levemir-2021.pdf page 11)

Do you vary your doses a lot? If not, have you considered switching to Tresiba? In my experience, this is a very stable insulin, very forgiving with timing. I can take my daily dose 6 hours earlier or later than usual without noticing an effect.
If your insulin needs fluctuate, it's not such a fitting insulin, it takes 2 to 3 days before a change in dosage becomes fully effective, no use if you regularly adjust for unusual days.

 

[jaimet]

But even if this would have been correct, you're happier taking it 3 times a day so taking it 3 times improves your quality of life. Which is the goal. It doesn't hurt them in anyway, why would they mind?

Because (as far as they're concerned) I'm effectively using it "off-label". All the official docs say "Once, possibly twice per day."

I can imagine you're angry with them. Even Novonordisks own information sheet on Levemir tells the action profile depends on the dose and twice a day administration may be necessary. (https://www.novonordisk.co.nz/content/dam/nncorp/nz/en/pdfs/datasheets/levemir-2021.pdf page 11)

And there, again, is the problem. Twice a day for something with a duration of action of less than 5.6 hours? What am I supposed to do for the other 12.8 hours each day? (I know the answer from bitter personal experience: have a fasting blood sugar in excess of 18mmol/L.)

Do you vary your doses a lot? If not, have you considered switching to Tresiba? In my experience, this is a very stable insulin, very forgiving with timing. I can take my daily dose 6 hours earlier or later than usual without noticing an effect.
If your insulin needs fluctuate, it's not such a fitting insulin, it takes 2 to 3 days before a change in dosage becomes fully effective, no use if you regularly adjust for unusual days.

I asked my endo-team regarding Tresiba a few years ago (when it first came out) and I was told that it was too expensive. I have just now looked at one CCG's "prescribing-support doc" and it says "restricted to those with an HbA1c > 58 mmol/mol" - my last HbA1c was 36 mmol/mol. I can always ask, however.

 

[Antje77]

And there, again, is the problem. Twice a day for something with a duration of action of less than 5.6 hours? What am I supposed to do for the other 12.8 hours each day? (I know the answer from bitter personal experience: have a fasting blood sugar in excess of 18mmol/L.)

I think after all this pushback I would be inclined to simply stop telling them I use it 3 times a day. Not the way it should be, and a missed opportunity for them to learn something, but also not worth your energy.