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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]
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.
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 ...
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 ...
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.
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 sulphonylurea , 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.
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 ]
Three classes of diabetes medications – GLP-1 agonists, DPP-4 inhibitors, and SGLT2 inhibitors– are also thought to slow the progression of diabetic nephropathy. [ 12 ] Diabetic nephropathy is the most common cause of end-stage renal disease and is a serious complication that affects approximately one quarter of adults with diabetes in the ...