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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]
GLP-1 agonists were initially developed for type 2 diabetes. [7] The 2022 American Diabetes Association (ADA) standards of medical care in diabetes include GLP-1 agonists or SGLT2 inhibitors as a first-line pharmacological therapy for type 2 diabetes in patients who have or are at high risk for atherosclerotic cardiovascular disease or heart ...
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.
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. The most common side effects include dizziness. [1]
To overcome this, GLP-1 receptor agonists and DPP-4 inhibitors have been developed to increase GLP-1 activity. As opposed to common treatment agents such as insulin and sulphonylureas, GLP-1-based treatment has been associated with weight loss and a lower risk of hypoglycemia, two important considerations for patients with type 2 diabetes.
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 ...
Other classes of medications include: sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists. [126] A 2018 review found that SGLT2 inhibitors and GLP-1 agonists, but not DPP-4 inhibitors, were associated with lower mortality than placebo or no treatment. [129]
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.
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