Page 60 - 51 the significance--29.2_opt

Figure 4. The mode of action of a DPP-4 inhibitor.

Administration

Crucially, in terms of patient convenience, DPP-4 inhibitors are orally
active. Furthermore, sitagliptin, saxagliptin, linagliptin and alogliptin
only have to be taken once a day, while vildagliptin is taken twice
a day. With many oral antidiabetic drugs (OADs), a dose-finding pe-
riod is required at the initiation of therapy, in which the most appro-
priate dose for a particular patient is determined. With DPP-4 inhibitors,
a dose-finding period is unnecessary due to the way in which they act,
the speed with which they act and the fact that gastrointestinal dis-
turbances, such as nausea and vomiting are not common problems.
These characteristics of DPP-4 inhibitors make them suitable for use in
combination regimens. 18-21

Efficacy

HbA lowering
1c
Currently, there are four DPP-4 inhibitors on the market: sitagliptin, vild-
agliptin, saxagliptin and linagliptin, while the arrival of alogliptin onto the
market is imminent. All of these agents have a unique mechanism of
action compared with the other OADs, namely their ability to potenti-
ate the activity of GLP-1 and enhance insulin secretion in a glucose-
dependent manner. Numerous randomised controlled clinical trials have
22
demonstrated that DPP-4 inhibitors can reduce HbA , fasting plasma
1c
glucose (FPG) and postprandial glucose (PPG) versus placebo. Tables
1–4 present some of the key information from the sitagliptin, vildagliptin,
saxagliptin and alogliptin clinical trials. The efficacy of linagliptin is dis-
cussed in some detail later in this chapter.

60