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DPP-4 inhibitors and GLP-1. Inhibitors of dipeptidyl peptidase 4 (DPP-4 inhibitors or gliptins) are a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4 (DPP-4). They can be used to treat diabetes mellitus type 2. The first agent of the class – sitagliptin – was approved by the FDA in 2006. [1]
[10] [8] Use in pregnancy and breastfeeding is not recommended. [10] Linagliptin is a dipeptidyl peptidase-4 inhibitor [8] that works by increasing the production of insulin and decreasing the production of glucagon by the pancreas. [8] Linagliptin was approved for medical use in the United States, [11] Japan, the European Union, Canada, and ...
Vildagliptin inhibits the inactivation of GLP-1 [2] [3] and GIP [3] by DPP-4, allowing GLP-1 and GIP to potentiate the secretion of insulin in the beta cells and suppress glucagon release by the alpha cells of the islets of Langerhans in the pancreas. It was approved by the EMA in 2007. [4]
Alogliptin, sold under the brand names Nesina and Vipidia, [2] [3] is an oral anti-diabetic drug in the DPP-4 inhibitor (gliptin) class. [4] Like other members of the gliptin class, it causes little or no weight gain, exhibits relatively little risk of hypoglycemia, and has relatively modest glucose-lowering activity. [1]
GLP-1 analogs resulted in weight loss and had more gastrointestinal side-effects, while in general dipeptidyl peptidase-4 (DPP-4) inhibitors were weight-neutral and are associated with increased risk for infection and headache. Both classes appear to present an alternative to other antidiabetic drugs.
One of the first reported DPP-4 inhibitor was P32/98 from Merck. It used thiazolidide as the P1-substitute and was the first DPP-4 inhibitor that showed effects in both animals and humans but it was not developed to a market drug due to side effects. Another old inhibitor is DPP-728 from Novartis, where 2-cyanopyrrolidine is used as the P1 ...
However, while DPP-4 inhibitors showed an increase in such risk factors, as of 2009, no increase in pancreatic cancer has been reported in individuals taking DPP-4 inhibitors. [ 26 ] In 2015, the US Food and Drug Administration (FDA) added a new warning and precaution about the risk of "severe and disabling" joint pain to the labels of all DPP ...
The most common side effects include urinary infections, nasopharyngitis, and upper respiratory tract infections . [5] [6] The most serious side effects include ketoacidosis (high blood levels of acids called ‘ketoacids’), pancreatitis (inflammation of the pancreas), hypersensitivity (allergic reactions) and hypoglycaemia (low blood sugar levels).