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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]
In 1999, Merck started a drug development program on DPP-4 inhibitors. When they started internal screening and medicinal chemistry program, two DPP-4 inhibitors were already in clinical trials, isoleucyl thiazolidide (P32/38) and NVP-DPP728 from Novartis. Merck in-licensed L-threo-isoleucyl thiazolidide and its allo stereoisomer.
However, weight gain and/or hypoglycemia have been observed when dipeptidyl peptidase-4 inhibitors were used with sulfonylureas; effects on long-term health and morbidity rates are still unknown. [42] DPP-4 inhibitors increase blood concentration of the incretin GLP-1 by inhibiting its degradation by DPP-4. Examples are:
Saxagliptin, sold under the brand name Onglyza, is an oral hypoglycemic (anti-diabetic drug) of the dipeptidyl peptidase-4 (DPP-4) inhibitor class. [1] [2] Early development was solely by Bristol-Myers Squibb; in 2007 AstraZeneca joined with Bristol-Myers Squibb to co-develop the final compound and collaborate on the marketing of the drug.
SGLT-2 inhibitors are relatively new drugs that treat type 2 diabetes. ... Compared with those taking DPP-4 inhibitors, participants on SGLT-2 inhibitors had a 35% reduced risk of developing dementia.
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 ...