Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

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Information about Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

The dipeptidyl peptidase 4 (DPP-4) inhibitors are a family of diabetic agents that enhance glucagon-like peptide-1 (GLP-1) activity, a gastrointestinal hormone (incretin) that increases glucose dependent insulin secretion.

Mechanism of action of Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

The DPP-4 inhibitors decrease the degradation of GLP-1 and thereby increase endogenous circulating levels. The increase levels of GLP-1 in the circulation increase pancreatic insulin secretion and improve glycemic control in patients with type 2 diabetes.

Liver safety of Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

The DPP-4 inhibitors have only recently been introduced into clinical use and the full range of adverse events may not be fully known. However, in prelicensure clinical trials, sitagliptin, saxagliptin, linagliptin and alopgliptin, the first four DPP-4 inhibitors to receive FDA approval in the United States, were not associated with an increase in serum aminotransferase or alkaline phosphatase elevations above the rates found in controls, and no clinically apparent acute liver injury was reported. Since licensure, isolated case reports of liver injury have arisen but liver injury from these agents appears to be rare and generally mild.

FDA approval information for Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

As of 2018, the four DPP-4 inibitors that are available in the United States include (with brand names and year of approval): sitagliptin (Januvia, 2006), saxagliptin (Onglyza, 2009), linagliptin (Tradjenta, 2011) and alogliptin (Nesina, 2013).


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