Another Medication for Type 2 Diabetes

Dr. Bill Quick Health Pro
  • I happened to notice that another medication for type 2 diabetes has been approved by the FDA (yawn!). It's getting to be an almost routine occurrence -- there are now eleven classes of medications for type 2 diabetes (insulin, metformin, sulfonylureas, thiazolidinediones, meglitinides, DPP-4 inhibitors, bromocriptine, GLP-1 receptor agonists, alpha-glucosidase inhibitors, colesevalam, and pramlintide). You don't recognize some of these? Don't worry -- I don't think anyone but a pharmacist or diabetes specialist would be familiar with all of them!


    The latest diabetes drug is called Tradjenta, and comes from Eli Lilly and Boehringer Ingelheim. Tradjenta's also known as linagliptin, and is the fifth approved drug in the class called DPP-4 inhibitors or "gliptins." The others are Januvia/sitagliptin, Galvus/vildagliptin (in Europe), Onglyza/saxagliptin, and Nesina/alogliptin (in Japan). The DPP-4 inhibitors work by inhibiting an enzyme called dipeptidyl peptidase 4 (DPP-4), which in turn enhances the effects of another group of hormones called incretins (which are inactivated by DPP-4); having more incretin allows increased insulin secretion, resulting in lower glucose levels. It's a Rube Goldberg series of steps, but it works: give a DPP-4 inhibitor, and glucose levels come down.

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    The DPP-4 inhibitors are weight neutral (causing neither weight gain nor loss) and relatively well tolerated. They do not cause hypoglycemia when used alone. They also have been studied in combination with other classes of diabetes drugs such as metformin, sulfonylurea and thiazolidinediones (and probably work well with other classes of diabetes drugs that have not yet been studied).


    The potential for this class of compounds to interfere with immune function and perhaps allow tumor growth is of concern, and one of the gliptins (vildagliptin) has never been approved by the FDA, although available in Europe, because of concern about skin lesions and kidney impairment seen in animal studies (but which apparently have not occurred in human trials). The FDA also has not approved alogliptin, requesting that further studies of possible cardiovascular risk be done.


    The question could be asked: why in the world would a drug company spend the time and energy to develop another drug in this class? The DPP-4 inhibitors are not really that effective: metformin is the clear leader in terms of effectiveness, and is recommended by treatment guidelines to be used soon after diagnosis of type 2 diabetes. The same guidelines dismissed the DPP-4 inhibitor class of medications as expensive, and pointed out that their long-term safety is not established.


    Back to my question: why confuse everyone with yet another gliptin when there are already a bunch of them available? A press release from the manufacturers lamely indicates one reason: "The FDA approval of TRADJENTA is exciting because there is only one dose to remember for all patients, regardless of kidney or liver impairment."


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    The more likely reason is the hope against hope of every manufacturer that their version of a drug will somehow strike gold. It's happened before: until Lipitor was on the market, it was assumed that it would be equal in efficacy to the other statins then on the market, but it was soon found to be a super-statin, and a latecomer to the statin market suddenly jumped to number one in sales. And it struck gold: in 2010, Lipitor captured $7.2 billion in sales. Back to the gliptins: I'm unaware of any reason to suspect that Tradjenta is more efficacious than the other gliptins; there's nothing in to indicate that linagliptin has been studied head-to-head against other gliptins.


    Or maybe it would be found to have less side effects. Again, there are historical precedents: Two glitazones (troglitazone and rosiglitazone) have been found to have devastating side effects, which the third drug in the class doesn't seem to have. Linagliptin apparently has a higher percentage excreted through the bile then the other gliptins, so maybe its safety profile will prove to be different.


    Or maybe it has a catchy name that's easy to pronounce, easy to spell, and makes some sort of sense. Not very scientific, but easy-to-remember names apparently do make a difference. (which brings up a point: I wonder how they chose "Tradjenta:" was it the name of the boss's pet dog or cat? Or was it a feeble attempt to choose a name that couldn't be mispronounced nor misrecognized when scrawled by a physician? For fun, try scrawling "Trojan" then "Trodjenta" and see the similarity -- at least these products are sufficiently different that a pharmacist would stop and doublecheck what the doctor really wanted to order.)


    Well, anyway, we now have another diabetes medication available. But it doesn't seem that exciting.

Published On: May 07, 2011