Back to the Future: Relearning How to Use Human Insulin

This transcript has been edited for clarity.

Jay H. Shubrook, DO: Hi. I'm Jay Shubrook, a professor of primary care at Touro University California in the College of Osteopathic Medicine and a diabetologist. I'm happy to have with me today Anne Peters, a professor at the Keck School of Medicine and the director of the Westside Center for Diabetes at USC.

Today we're going to talk about the emerging evidence regarding the use of human insulins as maybe the standard for the treatment of type 2 diabetes. Dr Peters, we're glad to have you here today.

Anne L. Peters, MD: Good to be here with you, Jay.

Shubrook: A recent study published in JAMA about use of human and analogue insulins in the treatment of type 2 diabetes in the Medicare population.^[1] So, tell me about this study.

Peters: It's a good question. The analogue insulins have become so expensive that many of our patients can't always afford them. The study basically looked at Medicare beneficiaries who had to switch and examined A1cs and reported rates of hypoglycemia.

We know it's hard to actually get reports of hypoglycemia. This is in part due to not coding every event, because you and I don't code every episode of hypoglycemia that happens. In fact, I rarely code hypoglycemia. Regardless, when the researchers looked at A1cs in this group of patients, they basically saw that there wasn't much of a worsening when you switch [from analogue to human insulin]. There was a little bit, but it was not clinically significant.

No matter what insulin you are on, if the A1c is still too high, your patient is not at target. Basically, the study showed that people who had to be switched from analogue insulin to human insulin could do so, generally safely.

While it is important to discuss what we think about this clinically, cost is—and will remain—an issue. I think we need to really discuss this in regard to our individual patients.

Shubrook: You bring up several important points. Even in this study, people didn't quite get to goal. However, at least there is a comparator, as patients using human and analogue insulins were handled relatively the same. Does that mean we should stop using analogue insulins?

Peters: I think this is somewhat confusing in terms of interpreting all the data. Clinical trial data is not flawed, but it is a different kind of data because all of those patients have study coordinators calling them up on the phone and getting them to titrate their insulin dose.

In clinical trials, you basically see a very similar reduction in A1c in people with type 2 diabetes, which is what we are discussing today, when you compare human with analogue insulins. You do, though, get less hypoglycemia when you use analogue insulin.

I think one of the reasons I tend to use analogue insulins when I can, particularly the basal analogues, is because I can uptitrate more confidently without causing hypoglycemia at night. I'm not calling my patients every day and bugging them to uptitrate and tolerate the hypoglycemia. I also like the fact that analogue insulins generally come in an insulin pen, which I find easier to teach—and for my patients, to use—than a vial and syringe.

That being said, I think we can get to similar A1c outcomes.

Shubrook: You and I both remember the days before analogue insulins and the work it took to take a patient from oral medications to vials of NPH and regular insulin, and then teaching them what schedule works with those insulins.

I would highlight that the older human insulins are clearly as potent as any insulin that's been made since. The challenge comes with the operationality of them. I remember the first time that glargine came out. I thought, Wow, this has to be so much simpler because you don’t have to dose at a certain time of the day and you can use a pen.

I want to highlight that because cost is an issue for some patients, we have to know how to use human insulins as well as analogues so that all of our patients can benefit.

Peters: You can usually get patients who are taking NPH (an intermediate-acting insulin) at bedtime down to something close to target. However, getting them to target without hypoglycemia at 2:00 or 3:00 AM can be a concern.

I tell patients that they may need to eat a snack at bedtime because that helps them not go low at night. However, that bedtime snack goes against everything I teach type 2 patients who are overweight and trying to lose weight.

We are saying the same thing: We have to be able to use human insulins. But there are ways that you have to think about using human insulins that are different. I am all about figuring out what is best for the patient. If they cannot afford an analogue insulin, they're not going to use it.

It is very important that we recognize that human insulin is effective. We can make it work, but we have to do it differently. I think that is the approach we all need to take. If market pressures make us increasingly likely to have to use human insulin, then we are going to have to get better at using it again.

Shubrook: This study really highlights that there may be increasing pressure from payers to use more human insulin. One of the things I do not think many people appreciate is that this not only means relearning the kinetics of those insulins but also going back to vials, and helping our patients be comfortable with vials because those cost savings really are amplified when we look at vials versus pens. It's going to be a different learning need, won't it?

Peters: Yes. I would encourage anyone prescribing insulin to teach themselves how to use a vial with a syringe. I remember once, when I was trying to get insulin pens on the formulary of an insurance plan, I actually had the head of the plan show me how to dose up 10 units with a pen versus 10 units with a vial and syringe. He got all flummoxed with the vial and syringe.

In good conscience, if we're teaching patients how to do something, we need to be able to show them how to inject air into the vial, pull it out, and to look to see that they have the right dose of insulin injected. That being said, I actually have some patients who have been using insulin forever who prefer using a vial and syringe because they can see exactly the insulin they are getting.

All of us need to be able to teach it. We need to be able to say to patients, "I know this is different but if you do this for a week, you'll learn it." Today there are YouTube videos that will teach everybody how to do this because you can watch someone else doing it. I think we need to avail ourselves of all the educational tools we have to teach our patients how to use a vial and syringe, and also how to mix insulins, because that's something that patients can do.

We also need to start telling patients that NPH insulin or any mixture with NPH in it is cloudy, and that is normal. If analogue insulin is cloudy, it's bad. Patients need to know that cloudy is good for human insulin, and they need to know how to mix it so that the insulin goes back into suspension before the patient gives the injection.

It does make them slaves to a different schedule than analogue insulin.

I actually find that after a week or so—maybe not even that long; it depends on the patient—patients get used to it.

The harder issue is patients with low vision and those who have arthritis. I have some patients who really can't easily use the vial and syringe. There are magnifiers and tools to help patients, but there are specific patients for whom I think that it is a bigger burden.

Shubrook: Today I heard some really important things. Emerging data remind us that human insulins are as potent as analogue insulins. Because of the substantial cost considerations of insulin today, it would behoove primary care providers to be knowledgeable about using human insulins for patients where it's a necessity, and certainly to have a minimum basic skillset for identifying good candidates and demonstrating how to safely use the insulin.

Thank you so much for your time today. I look forward to talking about the details of how to do this in our next conversation.

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