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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 ...
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] Rosiglitazone , a thiazolidinedione, has not been found to improve long-term outcomes even though it improves blood sugar levels. [ 130 ]
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 ...
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.
Medications based on incretins are used in the treatment of type 2 diabetes mellitus as well as the management of obesity.. Most of the earliest incretin-targeting agents to be approved fell into the class of DPP-4 inhibitors; these inhibit DPP-4 and thus prevent the enzymatic degradation of GLP-1 and GIP.
Exenatide (also Exendin-4, marketed as Byetta) is the first GLP-1 agonist approved for the treatment of type 2 diabetes. Exenatide is not an analogue of GLP but rather a GLP agonist. [32] [33] Exenatide has only 53% homology with GLP, which increases its resistance to degradation by DPP-4 and extends its half-life. [34]
Linagliptin, sold under the brand name Tradjenta among others, is a medication used to treat type 2 diabetes (but not type 1) in conjunction with exercise and diet. [8] [9] It is generally less preferred than metformin and sulfonylureas as an initial treatment. [8] [10] It is taken by mouth. [8] Common side effects include inflammation of the ...