Dpp-4 inhibitors

Oral antidiabetics are used for the treatment of diabetes mellitus type 2 DPP-4 inhibitors act antihyperglycemically by influencing the hormonal control circuit of insulin release by inhibiting the enzyme dipeptidyl peptidase-4 (DPP-4).

Insulin secretion is regulated, among other things, by the incretin hormone glucagon-like peptide 1 (GLP-1), which is produced in the intestine. The GLP-1 level rises postprandial. This stimulates the release of insulin from the beta cells of the endocrine pancreas. They are sensitized by GLP-1 to elevated blood sugar levels.

The glucagon-like peptide 1 is degraded to an inactive metabolite by the enzyme dipeptidylpeptidase-4. This reduces the release of insulin. The enzyme "dipeptidylpeptidase-4" degrades the hormone glucagon-like peptide 1 to an inactive metabolite and thus reduces the release of insulin. Inhibition of this key enzyme by DPP-4 inhibitors prolongs the period of elevated GLP-1 levels and thus insulin secretion.

Furthermore, extrapancreatic effects slow down gastric emptying and stimulate the feeling of satiety.

It has been observed several times that DPP-4 inhibitors can contribute to the onset of bullous pemphigoid. Among 217,331 cases in a French Pharmkovigilance Database (FPVD), 1,297 cases were found with DDP-4 inhibitors, and among these 42 cases involved bullous pemphigoid (vildagliptin: n=31; sitagliptin: n=10, saxagliptin: n=1). The side effects occurred with each of the DDP-4 inhibitors, which suggests side effects of the entire substance group (Phan K et al. 2020).

Sitagliptin (Januvia®, Xelevia®), vildagliptin (Galvus®, Eucreas®), saxagliptin (Onglyza®)