Comparing New Insulins to Older Formulations

Dennis P. Scanlon, PhD: Let’s move on to talk about today’s insulins. Insulin has been, obviously, around for quite some time. The insulins introduced today have qualities that are different from the products used years ago. How much of the newer insulins changed over the past decade? And really, how significant are those changes?

Zachary Bloomgarden, MD: I can weigh in, but everyone here has opinions. A number of years ago, I was an investigator in some of the initial trials of insulin glargine, which was introduced as Lantus, and really, it made a huge change in the way we treat diabetes. It’s a truly long-acting insulin, which in the majority of patients (certainly with type 2 diabetes), is dosed once a day, leading to fairly good control throughout the 24-hour period. And it has a modestly lower hypoglycemia risk than the older insulin, which was NPH (isophane). And that has allowed us to say, “Yes, starting insulin on people failing on 1 or 2 drugs is rational, useful.” And also, we continue the oral agents, or the GLP-1 (glucagon-like peptide-1), and add insulin, so we have at least a reasonable therapeutic pathway to follow. After insulin glargine came insulin detemir, which has the brand name Levemir. And that is quite similar (maybe has certain advantages and certain disadvantages), and those are the 2 long-acting, newer insulins that have been with us for most of the past decade-and-a-half or so.

Mary Ann Hodorowicz, RDN, MBA, CDE: I think, too, we have to look at the new rapid-acting insulins for meal dosing—pre-meal, correcting a high pre-meal blood sugar, the rapid-acting to adjust for how many carbohydrates you eat. That’s critical when you’re on multiple daily injections. And the analogs versus the synthetic human insulins—correct me if I’m wrong here to the physicians, but the analogs have better predictability and more accuracy with when it peaks, how long it lasts, and where it is at the onset. It’s predictable. It’s reliable. With the synthetic human insulins, you don’t know when it’s really going to kick in, how long it’s going to last, or when it’s going to peak, and that makes it difficult for the patient.

Zachary Bloomgarden, MD: Absolutely. If you look at how rapidly insulin goes into the bloodstream in someone who does not have diabetes, it’s up within a half hour, or 20 minutes. If you look at the rapidity of either high peak blood level after insulin lispro, Humalog, or insulin action using a glucose clamp (let’s say), really, the action profile with insulin lispro is around 40 to 60 minutes, which is a bit delayed over what the body would actually want. So, there are some newer insulins which have certain characteristics that allow them to be absorbed more rapidly.

Dennis P. Scanlon, PhD: We’ve talked about so many different types of insulin available today for clinicians to consider for patients. One of those would be the ultra-long-lasting insulins. What are some of the advantages of those therapies.

Zachary Bloomgarden, MD: Let’s talk about these 2 newer insulins, which are very interesting and do have some unique advantages. One of them is the more concentrated form of insulin glargine, U300 insulin glargine, and the other one is insulin degludec, which is a very interesting insulin with a fatty acid moiety that allows it to have very, very prolonged duration of action. With both of these products, there may be a little bit less variability of action. There may be a little bit of a smoother insulin curve. There are these treat-to-target studies against U100 insulin glargine (the older Lantus preparation). And, in both cases with both insulins, and in people with type 1 diabetes and type 2 diabetes on basal insulin alone and type 2 diabetes on basal bolus, basically every situation where a treat-to-target trial has been done, they’ve shown less nocturnal hypoglycemia (which is certainly good). Insulin degludec has the additional advantage that it really can be given at a different time of day on different days. So, if the person takes it one day in the morning, and then the next day forgets to take it in the morning but takes it in the afternoon, it actually works fine. And the flatness of it is such that you get fairly stable blood insulin levels without causing hypoglycemia.

Probably, it could be given every other day, but the study that tried to do it 3-days-a-week did not show that that worked because when you waited 2 days without insulin, it certainly didn’t last. But this absolutely offers an advantage for patients who have active lifestyles who might sometimes omit an insulin dose.

Another area where I’ve actually found it to be very useful is, since I do take care of a lot of older people, in an older individual who needs reminding or perhaps a family member administers the insulin. That person might get the insulin in the morning one day, but the family member might come in the afternoon the next. So, these really have advantages, and the evidence of decreased hypoglycemia is a good thing. Do they absolutely show an advantage where they should replace insulin glargine and the other insulins? Not really. They don’t show any lesser degree or weight gain. Overall glucose control is absolutely no better. So, I wouldn’t say that these are advantageous in the same way that moving from NPH to glargine was, but they certainly are useful.

Dennis P. Scanlon, PhD: Other thoughts?

Robert Gabbay, MD, PhD, FACP: Yes. I think it’s a matter of identifying the patients that will benefit the most. I think that’s a factor. I think adherence becomes another issue. If you have the ability to take it at different times a day, that may lead to greater adherence. And like any other insulin, if you take it, it works better than if you don’t.

Dennis P. Scanlon, PhD: Right. And Dr Snow, as a payer, I imagine these are tough decisions in terms of when to cover (as we’ve talked about in other segments)?

Kenneth Snow, MD, MBA: These are all tough decisions. What you hope is that as there’s additional insulin options available, that at least the pricing on them is not dramatically different such that the price doesn’t become the driving force but, rather, that the appropriateness for a particular patient becomes the driving force. So, that’s what you hope—is that nobody decides to try to overprice their product.

Zachary Bloomgarden, MD: As a clinician, I would just absolutely echo that and say that the worse thing with these new insulins would be if they led to further increases in cost for our patients. We just must avoid that, if at all possible.