The Evolving Role of Insulin in Type 2 Diabetes

Peter Salgo, MD: That brings us, if you will, to the use of insulin with type 2 diabetes. When I was in medical school, that just wasn’t done. And then its use became acceptable. Now, it’s considered great treatment. When is insulin needed in type 2 diabetes?

Julio Rosenstock, MD: Insulin is needed when the glucose control is not satisfactory, not sufficiently controlled despite the use of oral agents. The recommendation says to use metformin, all the different orals, and the other option, basal insulin. I don’t think people do it for the most part. People will use 2 agents and sometimes 3 agents. But if the A1C is above 7%, or 7.5%, I think that is time to consider insulin. I agree with Carol that we should do it much, much earlier. That’s really where the game changer came—with the use of insulin glargine. Insulin glargine became one shot a day, slowly starting with 10 units. When the decision was made to start 10 units, there was no science with that because it was very simple to use. It was titrated with some hypoglycemia, but much less hypoglycemia than NPH (isophane).

Robert Henry, MD: The use of the pen was an amazing advancement. It’s continued today with the combination therapies. That was the first time we started to use pens regularly.

Julio Rosenstock, MD: Yes.

Vivian Fonseca, MD: I think it’s important to recognize insulin deficiency. Someone with a very high A1C—10%, 9.5%, and above—they are insulin-deficient. And you can give all the other drugs you want; it’s an exercise in futility. You need to give a small amount of insulin to help those drugs work better, and they work very well in combination.

Peter Salgo, MD: What is early insulin initiation and who gets early insulin? What are the benefits of going on insulin earlier rather than later?

Julio Rosenstock, MD: Well, if we looked at all these studies of insulin initiation, most of these studies are testing insulin glargine, detemir, NPH, degludec, U300. You look at the demographics. You look at 10, 12 years of diabetes.

Carol Wysham, MD: Eight-and-a-half.

Julio Rosenstock, MD: It’s not about the time. It has to do with what the A1C is. If the A1C that was individualized is about what the patient and the physician wanted, despite the use of oral agents, it’s time to use insulin. And that’s early.

Robert Henry, MD: I would think some of our reasons for delaying the use of insulin has been because the previous insulins were very difficult to use, were associated with complications, and were not very effective. However, that’s changed. The insulins that we now have are very effective, long-acting, basal insulins. Rapidly acting analogs are very effective, and that’s allowed us to move the insulins earlier in the game. But in the past, insulin was always the last, and it was the last because it was the most difficult to use. But that’s not the case today.

Vivian Fonseca, MD: We also have pens with finer needles. It’s somewhat unfortunate that you often find patients on formulary. The insulin is covered, but the pen is not. And I think that’s really tragic because the incremental cost of a pen is very minimal.

Carol Wysham, MD: I think regarding the issue of early insulin administration, Julio talked about the fact that insulin is what’s missing. They’ve done studies, with even pre-diabetes and early diabetes, giving them insulin glargine. Their main reason for doing the study was a cardiovascular outcome study. But what we found out from that is if we start patients within 5 years of their diagnosis of diabetes, we can get their A1Cs below 6% and keep it at around 6% for 7 years (1.5 kg of weight gain over that 7-year period of time and very low rates of hypoglycemia). If a patient has endogenous insulin secretion and we’re just supplementing it by giving a little extra, they can tolerate it very well, and all of the baggage that goes along with insulin therapy is much less when you use it early. I always tell my residents that insulin is never the wrong answer. If you’re asking what we should do with that patient, insulin is never the wrong answer. It might not be the best, but it’s never wrong.

Julio Rosenstock, MD: Carol is referring to the ORIGIN trial that tested insulin glargine versus no insulin. Over 6 years, these people actually started very early. They had cardiovascular disease with a baseline A1C of 6.5%. They went over 6 years, and the A1C at the end was around 6.3% or 6.4%. So, insulin works very well and those are people very well controlled. Some of them even had pre-diabetes and accepted the 1 shot a day with a relatively low dose.

Vivian Fonseca, MD: Regarding the personalized goals that we talked about earlier, you wouldn’t actually use insulin at those A1Cs?

Julio Rosenstock, MD: Of course not.

Carol Wysham, MD: The point is, the earlier you use it in the course of diabetes, the better tolerated it is for the patient.

Peter Salgo, MD: Help me out here, and help our audience out. There are patients in whom early insulin is a great idea. Who would you start insulin on early?

Carol Wysham, MD: In the patient who has cost issues, I would use NPH insulin after metformin.

Julio Rosenstock, MD: I would not use NPH insulin. I think, now, with the biosimilars, they have come down. The insulin glargine, I think, is the way to go. And even the other ones, glargine U300 or degludec, those are more expensive.

Carol Wysham, MD: The cost is the expense. If I have a patient who has good insurance, I’m going to probably do an SGLT2 (sodium-glucose co-transporter-2), GLP-1 (glucagon-like peptide 1). I’m not going to get to insulin right away, but I’m just saying that there is a consideration. NPH insulin is very effective. In the Treat-to-Target study, there was no better A1C with glargine than NPH. The problem was nocturnal hypoglycemia. They get a little bedtime snack.

Robert Henry, MD: There are some healthcare organizations that still use NPH.

Carol Wysham, MD: Yes.

Julio Rosenstock, MD: Bob Henry said that we have better insulins, and so on. We have faster-acting insulins. I think that short-acting, fast insulins are way too complicated for the family practitioner.

Carol Wysham, MD: I totally agree.

Julio Rosenstock, MD: I think that when basal insulin is not enough, what we need to be using is a GLP-1 receptor agonist.

Robert Henry, MD: I agree with you.

Peter Salgo, MD: I heard you say something that surprised me, which was that insulin is expensive.

Carol Wysham, MD: It is very expensive.

Peter Salgo, MD: But that goes against everything I thought about insulin. To me, it’s old, off-patent, and easy.

Julio Rosenstock, MD: Ancient.

Vivian Fonseca, MD: This is a recent phenomenon. The price has gone up in the last 5 years, tremendously.

Peter Salgo, MD: Why?

Vivian Fonseca, MD: Well, Congress is investigating. I don’t know the answer.

Carol Wysham, MD: The reality is that there are middlemen now, between the pharmaceutical companies and the patient, that are taking a substantial amount of cuts from the cost. That’s part of the issue. But the reality is that all of the insulin analogs that have come out are better insulins; there’s no question about it. But the cost has been such that you can have a patient on a kind of average dose of insulin, and it’s as expensive as some of these newer drugs we’ve been talking about.

Transcript edited for clarity.