Combination Therapies for Treatment of Type 2 Diabetes - Episode 4
Value of DPP-4 Inhibitors in Type 2 Diabetes
Experts Javier Morales, MD, and Dhiren Patel, PharmD, CDE, BC-ADM, BCACP, reflect on the value of DPP-4 inhibitors, in terms of mechanism of action and availability in the treatment paradigm, for managing type 2 diabetes.
Javier Morales, MD: The DPP-4 inhibitor is an agent in the class of integrin drugs. It’s actually the inhibitor of an enzyme called dipeptidyl peptidase­—4, which is responsible for breaking down endogenously secreted glucagonlike peptide–1 out of the intestinal L cell. It is administered orally and could be instituted at any phase in the management of type 2 diabetes, either as monotherapy in those patients who may not be able to take metformin for whatever reason—whether it be because of limited renal function or perhaps because of intolerance—or as combination therapy with metformin. They could be available as combination therapy with other orally administered medications, as well.
These agents tend to be more weight neutral and have a very, very low risk of a hypoglycemic event, unless they’re used in combination with medications that could increase that risk of hypoglycemia, such as with the secretagogue class or even in combination with insulin. The DPP-4 inhibitor tends to be a fairly neutral agent to add. When you look at the head-to-head studies of DPP-4 agents compared with the secretagogue agents, noninferiority was actually conferred when looking at the efficacy of these 2 different classes of agents. So, they tend to be a little bit friendlier to use, they could be utilized at any stage of type 2 diabetes, and the risk of hypoglycemia could be averted by the use of these agents.
Dhiren Patel, PharmD, CDE, BC-ADM, BCACP: The mechanism of action of DPP-4 inhibition is that it actually inhibits an enzyme called DPP. By inhibiting this enzyme, what that allows is the increase in incretin hormones—specifically, GLP-1 and GIP (gastric inhibitory polypeptide). What this in turn does is stimulate insulin secretion and decrease glucagon, and the result is a decrease in your blood sugars.
There are a lot of benefits of using DPP-4 inhibitors. Some of them include it being an oral medication, and in patients who are unwilling to potentially inject, it’s a very good alternative to add on to metformin or other medications that the patient might already be on. Other benefits include its very low hypoglycemia risk profile. In my patient population, when I’m dealing with a geriatric population, that’s something of importance to me. And so, if you’re worried about a patient becoming low or if they’re by themselves, it has a really low hypoglycemia risk profile. Compared with a lot of the older drugs such as sulfonylureas and TZDs (thiazolidinediones) where we’ve see weight gain, these medications are weight neutral: A patient doesn’t experience any additional weight gain. Those would probably be the 2 biggest benefits and attractive features of this class.
The 4 DPP-4 inhibitors that are currently on the market are sitagliptin, saxagliptin, alogliptin, and linagliptin. All of these medications are taken orally, and they’re all dosed once daily. One note that’s important from a pharmacist’s standpoint is that most of them come in different strengths because of the renal dosing that’s required with these medications. The 1 exception to that rule in linagliptin, which does not require renal dosing, and for that reason it only comes in 1 strength.