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• W2080866420 abstract "Background: Sitagliptin phosphate, the first dipeptidyl peptidase 4 (DPP-4) inhibitor, provides a new treatment option for patients with type 2 diabetes. Objective: The purpose of this article is to review the pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, and cost of sitagliptin in adults with type 2 diabetes. Methods: A literature search of MEDLINE (1966-May 10, 2007), Iowa Drug Information Service (1966-May 10, 2007), and International Pharmaceutical Abstracts (1970-May 10, 2007) was performed using the terms sitagliptin and MK-0431. English-language, original research and review articles were reviewed, as were citations from these articles. The 2005 and 2006 American Diabetes Association Scientific Abstracts were searched, and the US Food and Drug Administration review of the new drug application for sitagliptin and select information from the manufacturer were consulted. Results: By inhibiting DPP-4, sitagliptin enhances postprandial levels of active glucagon-like peptide-1 (GLP-1), leading to a rise in insulin release and decrease in glucagon secretion from pancreatic α-cells. Sitagliptin is 87% orally bioavailable, undergoes minimal hepatic metabolism, and is primarily excreted unchanged (~79%) in the urine. At doses ≥100 mg QD, DPP-4 activity is inhibited by >80%, with a consequent 2-fold rise in active GLP-1 levels. The reduction in glycosylated hemoglobin (HbA1c) observed with 100 mg QD of sitagliptin in Phase III monotherapy trials ranged from ~0.5% to 0.6% (P ≤ 0.001 vs placebo). In Phase III combination trials, HbA1c was reduced by ~0.7% when added to metformin and ~0.9% with pioglitazone (P < 0.001 vs placebo). Markers of β-cell function, including proinsulin/insulin ratio and homeostasis model assessment of β-cell function, were improved with sitagliptin treatment. In studies, sitagliptin has been well tolerated; significant hypoglycemia and weight gain have not been noted. Conclusions: When used alone or in combination with metformin or pioglitazone, sitagliptin has been associated with significant reductions in HbA1c and has been well tolerated. Before its place in therapy can be firmly established, long-term studies evaluating the safety of prolonged DPP-4 inhibition are necessary." @default.
• W2080866420 created "2016-06-24" @default.
• W2080866420 creator A5020354607 @default.
• W2080866420 creator A5074073257 @default.
• W2080866420 date "2007-12-01" @default.
• W2080866420 modified "2023-10-16" @default.
• W2080866420 title "Sitagliptin phosphate: A DPP-4 inhibitor for the treatment of type 2 diabetes mellitus" @default.
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• W2080866420 doi "https://doi.org/10.1016/j.clinthera.2007.12.034" @default.
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