Specific DPP-IV inhibitors
The first DPP-4 inhibitor to reach the market was sitagliptin (Januvia®, Merck & Co., Inc.), and later vildagliptin (Galvus®, Novartis AG), saxagliptin (Onglyza®, Bristol-Myers Squibb) and linagliptin (Trajenta®, Boehringer Ingelheim) were launched.
All inhibitors have good oral bioavailability and a relatively long duration of action, such that once-daily dosing gives 70–90% inhibition of plasma DPP-4 activity over a 24-hour period, which is sufficient to fully protect the endogenous incretin hormones from degradation. All DPP-4 inhibitors have significant antidiabetic effects when given in monotherapy, and result in further improvement of glycaemic control when given in combination with other antidiabetic agents including metformin, sulphonylureas and thiazolidinediones. As opposed to the GLP-1 receptor agonists, DPP-4 inhibitor treatment does not result in weight reduction, but appears weight neutral. Keeping body weight stable during improved glycaemic control is in itself of interest, since the significant regulation in blood glucose they provide per se would be expected to result in weight gain (if not for other reasons, then because loss of glucose through the urine is prevented). The simplest explanation for the lack of effect on body weight is the fact that the concentrations of active GLP-1 obtained with the inhibitors are limited compared to what can be obtained with the GLP-1 receptor agonists.