COMMENTARY

New Insulins: Benefits and Challenges

Anne L. Peters, MD

Disclosures

December 11, 2015

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Today I'm going to talk about insulin. Now, you may have noticed that we have many more insulin products on the market than we have ever had before, and there are going to be even more products coming down the pike. I want to try to make sense of all of these different products.

New Concentrations, New Analog Products, and Biosimilars

Most of us are used to the traditional U-100 insulin; that's what insulin syringes are made for. Some of you may have heard of U-500 insulin, which is basically a 5-fold more concentrated regular insulin, and we reserve it for people who are very insulin resistant. It's harder to use because it's more complicated in the sense that you have to figure out the dosing with insulin syringes. Nevertheless, we have discovered that increasing the concentration of insulin can improve some of the qualities that we know are associated with insulin.

One of the newer insulin products is called Toujeo®, and it's actually insulin glargine, which we're used to, but instead of being U-100, it's U-300. As a visual, it comes in this box, which is this light green color with some black polka dots, and the pen looks quite different compared with that gray glargine or Lantus® insulin that you're used to. But they make it simple. Even though this is U-300, it comes in a pen where the dosing increments (defined by each click) are as if you're dosing just any old U-100 insulin. This doesn't come in a vial because that's where confusion is introduced when drawing it out with a syringe.

This new U-300 insulin glargine is somehow more concentrated, and it seems to cause less hypoglycemia; in fact, most of these longer-acting analogs cause less nocturnal hypoglycemia. They have steadier profiles compared with the insulin products we're used to, like U-100 insulin glargine.

I almost think it's better to think of U-300 insulin glargine as a new insulin. My patients get confused if I say this is an extra-concentrated insulin glargine. In this sense, using brand names simplifies things. If you put a patient on this insulin, this U-300 insulin glargine or Toujeo, what you're doing is really trying to smooth out that overnight blood sugar level, reducing some of the peaks that you might find with either insulin detemir or with U-100 insulin glargine, to give them less hypoglycemia and give them a smoother basal insulin effect.

There is another long-acting basal insulin that's going to come on the market called insulin degludec. It has been on the market in Europe for a couple of years, and it's coming to the United States. It has actually been approved for use under the brand name Tresiba®, and it's somewhat different from insulin detemir. It's modified in different ways, and it gives you a very long and stable basal insulin effect. So, these newer long-acting insulin products give you less hypoglycemia and a longer action. These are truly stable basal insulin products.

We also have changes in the rapid-acting insulin products. There's now U-200 Humalog® (insulin lispro), and this is what the box looks like. All of these boxes look different because these are newer insulin products, and we don't want people to get mixed up. It's interesting that when you dial it up in the pen, again, it's been made to act in the same units that we're used to. This is the Humalog U-200, and the real difference here is that it works just like the Humalog U-100, but you go through a pen much less quickly because it's more concentrated. In a patient who is on a lot of Humalog, this may actually make it easier, as they're going to use fewer pens, but clinically this acts a lot like Humalog U-100.

After this, we're going to get biosimilar insulin, and these products will have different names. Biosimilar insulin is sort of like generic insulin, but there is no "generic" insulin per se because biosimilars require a lot more testing for regulatory approval. It's hard to make these insulin products, so the biosimilars have actually been tested more than a routine generic medication would be and have been shown to be similar in activity as the original parent compound. There will be biosimilar insulin glargine, for instance, and these insulin products will be coming out in the future, but with different names.

We will have to wait and see what the pricing structure becomes of the biosimilar insulin products vs the traditional branded insulin products vs these newer, even more stable insulin products that are coming on the market. This all becomes somewhat confusing except for the pens, because they have dosing that we're all used to.

In many ways, these products are advances for our patients if they are having issues with hypoglycemia at night, are using very large doses of insulin, or are having trouble getting down to target.

Switching to Nonanalog Insulin to Save on Costs

Now I'm going to just switch for a second to another side of this issue. At this time of year, a lot of my patients get into the Medicare "donut hole," which means that these expensive analog insulin products just aren't covered anymore by their insurance, and they can't afford them. So, I switch them to nonanalog insulin products if they can't get the analogs.

The two nonanalog insulin products are regular insulin and insulin NPH (neutral protamine Hagedorn). These are human insulin products, but they are not analogs—that is, they are not modified in some way to change their activity. Now, I have a caveat in that I really think that people with type 1 diabetes need to stay on analog insulin, so if I can keep them on their analogs, their insulin glargine and their rapid-acting insulin, I do. But you can treat both type 1 and type 2 diabetes with the older nonanalog insulin products.

These nonanalog insulin products come in vials, and they can be obtained more cheaply for maybe $35 dollars a vial at, say, Walmart or Costco, and the deal with the vials is two-fold: First, you have to make sure that your patients know how to use a syringe to draw up the insulin. A lot of our patients are used to pens, so they may not know how to do it, and you may need to reteach them. Second, if they're using NPH insulin, which most patients will be, there's that cloudiness. That's the protamine, and people need to roll the NPH insulin vials or the pens so that they resuspend the insulin in the protamine. I think that, because we're so used to the analogs, we're not used to teaching with the nonanalog products that you need to resuspend the insulin so it's ready for the injection.

Then, because NPH is an intermediate-acting insulin and not a long-acting insulin or an ultra-long-acting insulin, I cannot switch it dose for dose. For example, if I have somebody on 60 units of insulin glargine once a day, I cannot just swap that out for 60 units of NPH insulin. It will make their blood glucose go too low. So, I'll give about two thirds of the insulin glargine as NPH insulin, or maybe even less. If I'm giving somebody about 60 units of insulin glargine at bedtime, I may cut back to 40 units of NPH insulin. I may even cut back to 30 units, but then I may carry it over and give them an NPH insulin dose in the morning as well, so they're taking NPH insulin twice a day as opposed to just once a day. The key to this is to lower the dose.

So, if you're switching from an analog to a nonanalog, make sure that you go down in dose, that the patient knows how to use a vial and syringe, and to dose adjust (that is, go up on the dose as you need to). Remember that the key difference is that you get more hypoglycemia on the nonanalog insulin products, and you've got to take into account patients' activity levels, so that you don't end up having a patient develop hypoglycemia at night.

I think we really need to understand both the good part of the development of these insulin products that have smoother and flatter profiles, and that cause less hypoglycemia, and then obviously also understand the needs of our patients in terms of their ability to afford these medicines. We can work together to make sure that our patients stay under control and get good diabetes care and avoid some of the problems with hypoglycemia that you may find when you switch from analog to nonanalog insulin.

This has been Dr Anne Peters for Medscape. Thank you.

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