DPP-4 inhibitor

Inhibitors of dipeptidyl peptidase 4, also DPP-4 inhibitors or gliptins, are a class of oral hypoglycemics that block DPP-4 (DPP-IV). They can be used to treat diabetes mellitus type 2.

The first agent of the class — sitagliptin — was approved by the FDA in 2006.

Glucagon increases blood glucose levels, and DPP-4 inhibitors reduce glucagon and blood glucose levels. The mechanism of DPP-4 inhibitors is to increase incretin levels (GLP-1 and GIP), which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels.

A 2014 meta analysis found no favorable or harmful effect of DPP-4 inhibitors on all-cause mortality, cardiovascular mortality, or stroke, but a marginally statistically significant increase in heart failure.

Drugs belonging to this class are:

Other chemicals which inhibit DPP-4 include:

Adverse effects, including nasopharyngitis, headache, nausea, heart failure, hypersensitivity and skin reactions. They may cause severe joint pain. In those taking sulphonylureas there is an increased risk of low blood sugar.

In response to a report of precancerous changes in the pancreases of rats and organ donors treated with the DPP-4 inhibitor sitagliptin, the United States FDA and the European Medicines Agency each undertook independent reviews of all clinical and preclinical data related to the possible association of DPP-4 inhibitors with pancreatic cancer. In a joint letter to the New England Journal of Medicine, the agencies stated that they had not yet reached a final conclusion regarding a possible causative relationship.

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