Switching to an Insulin-Based Combination

Vivian Fonseca, MD: There is a little bit of a nuance there where you’ve got to choose the right starting dose.

Carol Wysham, MD: Well, of course.

Julio Rosenstock, MD: It’s very interesting. Dr Fonseca referred to how you are going to adjust therapy. First of all, there’s a limitation with how much you can give. The cap of the insulin glargine/lixisenatide, or LixiLan, is up to 60 units. With degludec…

Carol Wysham, MD: …it’s 50.

Julio Rosenstock, MD: Insulin degludec/liraglutide is up to 50.

Vivian Fonseca, MD: You’re talking about the units of insulin?

Julio Rosenstock, MD: Yes, the units of insulin, because we only count the units of insulin. We don’t count micrograms.

Robert Henry, MD: But at least you know much you get. You get the full therapeutic dose at the top dose.

Julio Rosenstock, MD: At the top dose.

Robert Henry, MD: For example, 60 units with insulin glargine/lixisenatide means you get 60 units of insulin and 20 micrograms of lixisenatide. With liraglutide, you get the 1.8 together with the 50 units of insulin.

Julio Rosenstock, MD: Correct. But the beauty about this is that you go slowly, with the adjusting of the insulin, and then you go slowly with the micrograms or milligrams…

Robert Henry, MD: …together.

Julio Rosenstock, MD: My patient is taking 42 units of insulin, of glargine, and you said it’s very easy. But how do we do the switch? So, they have the rule of “30s.” If you are taking more than 30 units, you start with 30 units and 10. If you are taking below 30, you start with 20 units and 5. That will be the correlate, 15 and 5.

Peter Salgo, MD: Just to be very clear, which formulation are you talking about?

Julio Rosenstock, MD: The rule of the 30s, adjusted, is for the LixiLan, insulin glargine/lixisenatide. For the insulin degludec/liraglutide, you start with 16 units no matter what. You can be at 42 units and go down to 16 units. So, there is a little bit of discrepancy. You start much lower with the insulin glargine. We don’t know how people are going to react when they say, “ I’m going to go from 42 to 16,” or, “42 to 30.”

Carol Wysham, MD: They actually looked at that, and they saw very little reduction or deterioration of glucose control.

Robert Henry, MD: Maybe because you’ve got 2 compounds at the same time.

Carol Wysham, MD: Right.

Julio Rosenstock, MD: Or maybe because you did not report it, because we have nothing in the reports.

Vivian Fonseca, MD: In a study, they knew they were going to titrate, whereas in practice, we hope you do now.

Julio Rosenstock, MD: It’s for both of them. In practice, we’re cutting back on the insulin. You’re going to use this, and this, and you cut down on the insulin. The blood sugar goes up, at first, and by the second week, you’re going to say, “Oh, this thing isn’t working.”

Peter Salgo, MD: You mentioned there was the LixiLan-O trial and the LixiLan-L trial. What was the difference there? What did they show?

Julio Rosenstock, MD: LixiLan-O is for oral agents. LixiLan-L is for people on basal insulin.

Peter Salgo, MD: I understood that. My question was, what were the results?

Julio Rosenstock, MD: The LixiLan-O goes down in the combination from 8.1% to 6.5%. The other goes down from 8.5% or 8.4%, down to 6.9%. In somebody who has 12 years of diabetes, who’s been on insulin for 3 years, it’s a pretty darn good result. But, to be fair, we get the same results with the other one—the insulin degludec/liraglutide. You get down. They have the DUAL-1 study, which has pretty similar results to the LixiLan-O trial, and they have the DUAL-2 study.

Carol Wysham, MD: I want to make it easier. Can you just say the difference, the additive difference of the GLP-1 (glucagon-like peptide 1) receptor agonist to the basal insulin gave an additional 0.6% to 0.7% reduction in A1C?

Transcript edited for clarity.