Posted by Jeff Berk, BOLT International; I got a question by email from a blog reader wanting to know what BOLT’s Diabetes Thought Leader panel thinks of Ondero (linagliptin). So, short and sweet — the following is some insight from some of the investigators who are working with the drug. Punchline: Boehringer-Ingelheim will position linagliptin as a better choice than sitagliptin in the diabetic with renal impairment. The basis will be that there is no need for the physician to remember any dose adjustment algorithm with linagliptin. This will niche linagliptin as a drug for those patients who aren’t candidates for Januvia or Onglyza, and who aren’t so advanced that they should be on insulin. One panelist estimated that renal impairment with moderate diabetes represents 5% of the T2D market. Another panelist said that he would still be cautious about using Ondero in patients with renal impairment. Linagliptin is producing HbA1c reductions in the 0.5% – 0.6% range. Net, Onglyza will be “number three on the block”, with a marketing “hook” but not clinical superiority.
“In fact, Boehringer Ingelheim, their one (linagliptin) is supposed to be relevant in terms of the renal impairment. The problem that we have is because we are an academic center we do moderate the drugs according to the renal levels but I suspect that when I go out in the community and talk to the doctors on this topic that very few of the primary care are actually adjusting doses, which may or may not be a problem. I am not sure. I am sort of skeptical. Maybe it is not going to be a problem. On the other hand, theoretically according to the studies on the black box you are supposed to adjust. So the Boehringer Ingelheim is going to come on as not requiring adjustments, but on the other hand I am not sure it adds very much to the total picture. Sort of number three on the block”.
“And do you feel like there is an advantage with the newer ones because of the renal clearance? Either Onglyza or even the one that Boehringer Ingelheim has in production, Ondero? I don’t think so. I am not going to rush in and say well I can forget about renal clearance just because they say there is very little renal clearance. I would actually err on the side of conservatism”.
“Boehringer Ingelheim is going to be coming up this spring in front of their advisory board with linagliptin. This is my naivety perhaps, but the only real advantage I see versus sitagliptin is that they don’t need to change their dose with renal impairment. Am I missing something? Not quite. I think that is largely the case, but it is not just a question of not changing the dose. The fact that you don’t have to change the dose does convey in doctor’s minds that it is a safer and easier thing to use. They can use it without thinking about it if you like. So it is a little bit more than just not changing the dose. It also makes it generally easier to use and there is a perception of it being easier to use, which means if people will end up using it even in people who don’t have normal renal function.
Given that you seem quite comfortable with the sitagliptin profile what is it, and you made the comment that saxagliptin doesn’t really offer you any new benefit. What is your expectation for linagliptin, the Boehringer Ingelheim drug? Exactly that. I think they have to be very clever in order to market this into the diabetes market. Remember the diabetes market is full of people with renal impairment; full of elderly people who might have renal impairment. So what they have to do really is get the marketing right subtly to say in the elderly it even has an advantage over sulfonylureas of course. In the elderly it has an advantage over sitagliptin because of the renal issue. So here is the drug you can just prescribe and forget it.
“As an expert in this area do you find that compelling? It is not compelling at all, but it is real life. That is exactly how people tend to behave”.
“The thing is that most diabetics by the time they have renal impairment to the point where you have to change dosing they are at a more advanced stage of diabetes and a lot of them are already on insulin and you are not even going to have them on oral drugs or at least not a DDP4 inhibitor. I think it is a niche. There are a certain percent of diabetics that aren’t that severe that have renal impairment, but I think that is going to be under 5 percent of the diabetic marketplace. And yes, there is a lot of renal disease in diabetics and those people are more advanced and they need stronger medications than just a DDP4. This and the TZDs are the weakest drugs that are on the market right now”.
“Linagliptin, that Boehringer Ingelheim is developing, supposedly won’t have any problems with renal impairment. Do you see that as a big issue or not? They asked us actually to be part of their phase III study and we declined to do it because we didn’t have the time or the resources. We had enough of those studies going on. It looks like that compound is a lot more specific to DPP4 and inhibits DPP4 more than sitagliptin or saxagliptin. I just don’t know, but if it is getting metabolized in the liver like vildagliptin (Galvus) does then maybe that is part of the reason for it. I don’t know. Or the dose that they are using since it is more specific they have a dose that gets cleared through the kidney at any GFR, so it is not an issue. That is what I suspect is going on”.
“And what sort of A1C reduction do you need to see from linagliptin to in your mind move it beyond sitagliptin? Both sitagliptin and saxagliptin right now are saying about 0.6, some of them say 0.7. I think someone needs to give a full percent. 1 percent will definitely impress people”.