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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]
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 ...
Another class of anti-diabetes drugs, DPP-4 inhibitors, work by reducing the breakdown of endogenous GLP-1, and are generally considered less potent than GLP-1 agonists. [3] Some of the metabolic effects of GLP-1 agonists in rodents are mediated via increased synthesis of fibroblast growth factor 21 . Pharmaceutical companies have developed ...
Commercially known as Ozempic (semaglutide), is a medication that belongs to a class of drugs called glucagon-like peptide-1 receptor agonists (GLP-1 RAs). It is primarily used for the treatment of type 2 diabetes and has shown potential benefits in addressing obesity as well.
The GLP-1 analogs principally act as agonists of the GLP-1 receptor and are thus insulinotropic. Exenatide was the first drug in this class to be used in the treatment of type 2 diabetes; it first received FDA approval in 2005. More recently, longer-acting and more potent GLP-1 analogs have been developed, most notably semaglutide, which ...
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 Australia in 2011.
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]
Omarigliptin (MK-3102) is a potent, long-acting oral antidiabetic drug of the DPP-4 inhibitor class used for once-weekly treatment of type 2 diabetes and currently under development by Merck & Co. [1] It inhibits DPP-4 to increase incretin levels (GLP-1 and GIP), [2] [3] [4] which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying and decreases ...