Sticky What is the Insulin Depot?

You may have heard reference to the Lantus or Levemir (or the glargine biosimilars like Basaglar and Semglee) Insulin Depot. What does that mean?

Lantus (and the biosimilar versions of glargine -- Basaglar and Semglee) and Levemir fall into the category of “depot drugs.” Pharmacologically, the insulins work in different ways, but each have the characteristic of being absorbed slowly by the body. The result is an extended action. These insulins tend to display a cumulative effect, meaning that what happens in one cycle can affect the next cycle, or even the next several days. This is part of what allows Lantus, Basaglar, and Levemir to create those beautiful, flat curves, so it is worthwhile to spend the time to understand the depot.

A depot injection is a blanket term for an injectable form of a medication which releases slowly over time to permit less frequent administration of that medication. They are designed to increase medication adherence and consistency especially in patients who commonly forget to take their medicine. The most frequently used depot injections are antipsychotic medications and contraceptive drugs which may require anywhere from a 1 – 3 month injection. Most of these types of medications have been studied in humans rather than cats.

While not true depot drugs, glargine (and its biosimilar forms) and Levemir have a strong similarity in that they are slowly absorbed by the body. Lindauer et al. (2019) note that glargine is designed to form a precipitate after being injected and those microcrystals are then slowly absorbed over a longer period than regular insulin. While their mechanisms of action differ, both glargine and detemir have an extended period of action. These insulins tend to display a cumulative effect, meaning that what happens in one cycle can affect the next cycle, or even cycles over the next several days. This is this action that allows Lantus and the glargine biosimilars (i.e, Basaglar and Semglee) and Levemir to create those beautiful, flat curves, so it is worthwhile to spend the time to understand the depot.

Here is a great reference that explains the Lantus and Levemir depots in layman’s terms:

Lantus and Levemir: What’s the Difference?

Glargine (Lantus, Basaglar, Semglee, and biosimilars):
Note: Lantus, Basaglar and Semglee are different brand names for insulin glargine.

Detemir (Levemir):

Have you ever wondered why, when you are giving the same amount of insulin every time, the response is different in each cycle? Sometimes the numbers go up for the whole cycle, sometimes they go down, sometimes they stay flat, and sometimes they actually “curve.” The answer often lies in the depot. Did you skip a shot or give a partial shot at some time in the past few days? That can result in higher numbers for several days as the depot replenishes some of its lost stores. Did you increase the dose? This can result in a change in the size of the depot and can lead to a temporary adjustment in the amount of insulin available for use. Did you decrease the dose recently? A dose reduction will usually result in a need for less stored insulin. The excess may be released into the bloodstream faster than usual, especially if several dose reductions are done back-to-back.

Absorption
Gradel and colleagues (2018) note that absorption can be affected by the composition of the tissue layers, the physical-chemical composition of the insulin along with the type of insulin, the concentration and volume (i.e., dose) of the insulin, and insulin injection technique and site. Not all of these factors are easily controlled which is why every insulin dose may not produce identical results. To further add to the challenge, it is difficult to estimate how long it takes both for the “depot” to form at the outset but also how long it will take for a dose change to stabilize.

Practical experience on FDMB shows that as a generalization, the depot can affect up to 6 cycles. The time tends to be less when a cat is on a smaller dose, and more when a cat is on a larger dose. Other factors can apply as well, but using the generalization of 6 cycles is a good starting point until you have learned your particular cat's patterns.

Now you are probably asking "How on earth can I use this information to understand my cat?"

Try to look at your spreadsheet not in 12-hour cycles, but in “waves” of action over a period of several days. Look for overall trends more than individual numbers. If something jumps out and doesn’t seem to make sense, go back 2-3 days and think about any changes that might have occurred in insulin, timing, exercise, health, food, etc. If the big picture is making sense but you see one cycle that doesn’t fit, then keep that 20-50% variation in mind and just wait it out.

More reading about the glargine and detemir depots:

• Internet Journal of Endocrinology: Insulin Detemir and its Unique Mechanism of Action
• Textbook of Diabetes Mellitus by B. B. Tripathy
• The Mechanism of Protraction of Insulin Detemir

Additional note:
The Insulin Depot is not to be confused with Carryover (insulin effects lasting past the insulin’s official duration) and Overlap (the period of time when one insulin shot is diminishing and the next is taking effect).

References:
Lindauer, Klaus, Becker, & Reinhard (2019). Insulin depot absorption modeling and pharmacokinetic simulation with insulin glargine 300 U/mL. Int. Journal of Clinical Pharmacology and Therapeutics, 57(1), 1-10.


K. J. Gradel, T. Porsgaard, J. Lykkesfeldt, T. Seested, S. Gram-Nielsen, N. R. Kristensen, & H. H. F. Refsgaard. (2018). Factors affecting the absorption of subcutaneously administered insulin: Effect on variability. J of Diabetes Research, Published online 2018 Jul 4. doi: 10.1155/2018/1205121

~ written by FDMB member, Libby and Lucy
edited by Sienne and Gabby (GA), Marje and Gracie, Wendy&Neko (2021)



Please be aware: There are not any "dose advisers" or "experts" on the FDMB. The FDMB is an open board subject to peer review where laypersons with varied degrees of knowledge and experience are free to share their own thoughts and opinions through explanation and by making suggestions.

We are not veterinarians. It is not our intention to take the place of your veterinarian. Please discuss dosing, methods, medications, and care for your cat with your veterinarian.

 

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