Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES, and Thomas C. Blevins, MD, ECNU, FACE, FNLA, review FDA-approved basal insulins for the management of diabetes.
Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: Welcome to this Endocrinology Network® and Drug Topics presentation titled “Interchangeable Insulin Biosimilars: A Game Changer in Diabetes Management.” I’m Diana Isaac from Cleveland Clinic in Cleveland, Ohio. I’m joined today by Dr. Thomas Blevins from Texas Diabetes and Endocrinology in Austin, Texas. Our discussion will focus on insulin therapy and approval of the first interchangeable insulin biosimilar. We’ll also discuss the role of biosimilars in endocrinology. Welcome, and let’s begin. Tom, I want to start by asking you to just briefly describe the pathophysiology of diabetes and the whole rationale for insulin therapy.
Thomas C. Blevins, MD, ECNU, FACE, FNLA: Thank you for asking, and thanks everyone for listening. This is interchangeability, which we’re going to get to; it’s a big deal. Pathophysiology in type 1 diabetes is straightforward. People don’t make insulin; therefore, they need insulin replacement and a hormone replacement treatment. We use basals and bolus, and we use insulin pumps and things like that. They have to have insulin. If they’re using multiple daily injection, then they’re going to need to have a basal insulin. We’ll talk more about those in a minute. For type 2 diabetes, many people don’t need insulin at all. They don’t make enough insulin, as you all know. We do use insulin in those who can’t control with other means. We use basal, and we use the bolus pre-meal. Sometimes we need basal alone to give them that supplemental amount, to give them just enough to get the control we want. So they are 2 different pathophysiologies. Both need insulin, but not everyone with type 2 needs insulin.
Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: All great points. People with type 1 diabetes are always going to need kind of a basal and a bolus. As we see, people with type 2 diabetes are being diagnosed earlier in life. Through the natural progression of diabetes, even though we have a lot of great noninsulin medications, it’s very natural that over time people do need to supplement with insulin. Very commonly, we start with a basal insulin. Many people progress to needing a bolus insulin with type 2 diabetes as well. With that, I’m hoping that you might be able to provide us with maybe a brief historical overview of the FDA-approved basal insulins.
Thomas C. Blevins, MD, ECNU, FACE, FNLA: You may be saying I’m a little historic. But you’re probably right. I was in training in the 1980s and medical school starting in the 1970s. I’ve seen, as many of us have, quite a bit of evolution. We had long-acting insulins, like Ultralente—most people don’t even know what that is nowadays. Don’t even try to know by the way—let me give you that advice. It was once a day. For the most part, though, we used an insulin, the Neutral Protamine Hagedorn, the NPH, which was the protamine-based insulin that was more of an intermediate acting. We called it basal. The way we used it back then—diabetes management was an art and a science. A little more art than science sometimes because with NPH you had to use multiple doses to get any a leveling in the background. NPH was a true mess. It would peak in 6 to 8 hours, and then it dropped off after 14 to 16 to 18 hours depending on the dose. I’d have some patients use NPH in the morning, some at dinner, and some at bedtime to try to spread out the effect.
Then, about 20 years ago, came detemir, which is a once a day. It’s an insulin that we use now. I’ll say the drug name Levemir [insulin detemir] because people are familiar with that name. It lasts for about 24 hours. Then along came insulin glargine. You add a glycine to the A chain of insulin and 2 arginines to the B chain, and voilà—you have an insulin that lasts longer, and you get into this manipulation of the molecule to make it work better and longer and to suit our needs better.
Glargine came along; it’s once a day. That was a huge change. We had much more predictable usage of basal. glargine is probably the most commonly used basal around the world at this point. I think that’s true. Later, around 2005 or so, we got degludec, which is Tresiba [insulin degludec]. Then we got the U300 glargine, and we got that 10 or 15 years ago. So we’ve had this nice evolution of where we’re going with basal insulin.
We use these in people with type 1. We try to simulate physiology as best we can. That’s what we try to do. We use them in type 1, and we use them in type 2 to get our basal effect. We’re not going to talk about bolus much here, but we’re talking basal. We’ll get into this as we talk more about these in a minute. Now we’ll get into the biosimilars that will offer some better access and affordability.
Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: Thanks. Those are all great points. Having an insulin that truly can last 24 hours a day has been a big game changer in diabetes because back with the NPH, patients had to dose it twice a day, and it’s challenging to remember to take something that many times. Unfortunately, it would wear off before 24 hours, and then your glucose levels go up. So it was much more challenging. It’s so nice to have basal insulins that can truly last 24 hours or even longer than 24 hours that we see with degludec and with glargine U300, the more concentrated version.
Transcript Edited for Clarity