期刊
AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY
卷 65, 期 6, 页码 521-531出版社
OXFORD UNIV PRESS INC
DOI: 10.2146/ajhp070248
关键词
antidiabetic agents; combined therapy; diabetes mellitus; dosage; drug interactions; mechanism of action; metformin; pharmacokinetics; sitagliptin; thiazolidinediones; toxicity
Purpose. The pharmacologic, pharmacokinetic, safety, clinical efficacy, and role of sitagliptin in the management of type 2 diabetes mellitus are reviewed. Summary. Sitagliptin is a dipeptidylpeptidase IV (DPP4) inhibitor that increases insulin release and decreases glucagon levels by preventing the activation of incretin hormones-glucagon-like peptide-1 and glucose-dependent insulinotropic poly-peptide. The clinical trials reviewed provide evidence that sitagliptin, either alone or in combination with metformin or thiazolidinediones, is effective in reducing glycosylated hemoglobin (HbA(1c)), fasting plasma glucose, and two-hour postprandial glucose levels in patients with type 2 diabetes. Specifically, sitagliptin has a role in patients who have been compliant with their oral hypoglycemic agents but unable to attain target HbA(1c) values with monotherapy and lifestyle modifications. Sitagliptin is generally well tolerated, with the frequency of adverse events being similar to placebo and a low frequency of hypoglycemia. Sitagliptin does not appear to alter the pharmacokinetics of metformin, rosiglitazone, glyburide, simvastatin, warfarin, or oral contraceptives. The addition of sitagliptin to a patient's oral antidiabetic regimen would necessitate close monitoring for adverse events and possible drug interactions. The sitagliptin dosage recommended by the manufacturer is 100 mg once daily as monotherapy or in combination with metformin or a thiazolidinedione. No formal pharmacoeconomic evaluations of sitagliptin therapy have been conducted. Conclusion. Sitagliptin, a DPP4 inhibitor, offers a novel treatment option for patients with type 2 diabetes mellitus.
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