LixiLan Trials in Type 2 Diabetes

Peter Salgo, MD: You were talking about lixisenatide, and then you mentioned there was a combination product the FDA was looking at, too. That’s lixisenatide plus insulin glargine?

Carol Wysham, MD: Right.

Peter Salgo, MD: How does that all fit in? Where are we with that?

Carol Wysham, MD: I’m going to defer your question to Julio, because he did all the studies with it.

Vivian Fonseca, MD: But before we get there, lixisenatide has been tested with other agents, as well, in the GetGoal program. It’s a broader program. It’s not widely used.

Julio Rosenstock, MD: No, I think it was tested because of regulatory in combination with metformin—metformin and sulfonylureas. But if I were to use lixisenatide, I would use it in combination with basal insulin.

Vivian Fonseca, MD: I totally agree.

Julio Rosenstock, MD: For the oral agents, you have other options there that work very well.

Peter Salgo, MD: So, there’s a combination?

Julio Rosenstock, MD: Yes, there’s a combination for this program. It’s called the LixiLan program. There is the LixiLan-O and the LixiLan-L trial. We’ve been involved in both the trials, and here’s the combination of insulin glargine plus lixisenatide in 2 different ratios: 2:1 or 3:1. For 1 unit of insulin, you have 2 micrograms, or so on, or 3 micrograms. But it’s 2:1 or 3:1. The point is, you give it in combination. The LixiLan-O trial is for people who failed 2 oral agents. It was comparing LixiLan (that has a combination of insulin glargine plus lixisenatide), versus insulin glargine alone, versus lixisenatide alone—it’s really head-to-head active comparators. And the results were very robust in terms of what you can get there. You have a reduction from an A1C of 8.1% to 6.5% with the combination of the 2.

Peter Salgo, MD: Let me just stop you. That is an impressive number.

Julio Rosenstock, MD: That is pretty darn good, because it’s associated without weight gain and without the increasing hypoglycemia. Now, if you want to use insulin alone, that’s fine, because it did get it to 6.8% (but with weight gain). If you want to use the lixisenatide alone, that’s fine, but it gets down to 7.3%. But you get down to 6.5%.

Now, the FDA did not approve insulin glargine/lixisenatide in combination with oral agents. It did approve it in people who did not get good control with basal insulin. And for people who want to know about that, you can only use it in people who have basal insulin and need to advance therapy. And so, you switch to that. When you do that, they compare the basal insulin with insulin glargine, versus insulin glargine, insulin glargine/lixisenatide. And then you get people who were from 8.5% down to 8.1%, and then you get down to 6.9% when you do the switch. And, if you continue intensifying the insulin glargine, you get to 7.5%.

Robert Henry, MD: Julio, can I ask you a question? In those studies that you’re talking about, where they were comparing the combination, LixiLan, or insulin glargine/lixisenatide, to either of the components, they had a run-in period.

Julio Rosenstock, MD: Correct.

Robert Henry, MD: A run-in period of 4 or 6 weeks where they took people and titrated them as much as they could. Do you think they would have even gotten more reduction? Because I noticed that in some of the other trials done with degludec, they didn’t have a run-in period.

Julio Rosenstock, MD: Correct. There’s a difference because both formulations are great. You see the same impressive results you get in insulin glargine/liraglutide, which again, is in people in similar design. For people who fail oral agents, who remain on metformin, then you put them on insulin degludec and liraglutide, versus insulin degludec, which is degludec alone, or liraglutide alone. You still get down to 6.5%, but the degludec, in this case, went down to 7%. The delta looks a little bit greater. But, again, both get to around 6.5%, except that there’s a difference—they did that right from the beginning, whereas in the insulin glargine/lixisenatide combination, they had a period of 6 weeks of optimization of the insulin. So, they brought it down from 8.5% to 8.1%, and then continued with the glargine down to 7.5% versus 6.8%.

Vivian Fonseca, MD: There are some new studies that are ongoing, which are using the combination right up front.

Julio Rosenstock, MD: But, I mean, those are little, intrinsic studies.

Vivian Fonseca, MD: It’s important, though, because you need those studies because the label, right now, for both combinations is to use the combination when one has failed.

Carol Wysham, MD: Either GLP-1 (glucagon-like peptide 1) or insulin, yes.

Vivian Fonseca, MD: That’s a limitation.

Julio Rosenstock, MD: Sure. It’s a limitation, but I think it’s all right because it’s the low-hanging fruit. A lot of practicing physicians out there, as we said before, have done very well. I give credit to the practicing physicians out there who use basal insulin, but they are frustrated. They are frustrated because they cannot get to the goals that they want. And when they need to advance, they don’t want to use prandial insulins here. Switching to a co-formulation allows for the chances to advance therapy, and that’s why the FDA approved the indication.

Carol Wysham, MD: I was just going to say that it’s really easy, also, for the patients. You’re basically taking them from something they’ve been doing every day (it happens to be a little different of a formulation), and you talk a little bit about where to start, and they continue to titrate it. They’ve already done it. The actual education part is minimal.

Transcript edited for clarity.