CLINICAL REVIEW Sitagliptin 521 Am J Health-Syst Pharm—Vol 65 Mar 15, 2008 CLINICAL REVIEW DAVID Q. PHAM, PHARM.D., BCPS, is Assistant Professor of Pharmacy Practice, College of Pharmacy and Health Sciences, Western Univer- sity, Pomona, CA, and Research and Clinical Education Coordinator, Fountain Valley Regional Hospital and Medical Center, Fountain Valley, CA. ANNA NOGID, B.S., PHARM.D., BCPS, is Assistant Profes- sor of Pharmacy Practice, Arnold & Marie Schwartz College of Phar- macy and Health Sciences, Long Island University, Brooklyn, NY, and Critical Care Specialist, Brookdale University Hospital and Medical Center, Brooklyn. RODA PLAKOGIANNIS, B.S., PHARM.D., BCPS, is Associate Professor of Pharmacy Practice, Arnold & Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, and Clinical Pharmacy Manager—Primary Care, Montefiore Medical Group, New York. Address correspondence to Dr. Pham at the College of Pharmacy and Health Sciences, Western University, 309 East Second Street, Pomona, CA 91766-1854 (dqpham@westernu.edu). Copyright © 2008, American Society of Health-System Pharma- cists, Inc. All rights reserved. 1079-2082/08/0302-0521$06.00. DOI 10.2146/ajhp070248 Sitagliptin: A novel agent for the management of type 2 diabetes mellitus DAVID Q. PHAM, ANNA NOGID, AND RODA PLAKOGIANNIS Purpose. The pharmacologic, pharma- cokinetic, safety, clinical efficacy, and role of sitagliptin in the management of type 2 diabetes mellitus are reviewed. Summary. Sitagliptin is a dipeptidyl- peptidase IV (DPP4) inhibitor that increases insulin release and decreases glucagon lev- els 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 thiazoli- dinediones, is effective in reducing glyco- sylated hemoglobin (HbA 1c ), fasting plasma glucose, and two-hour postprandial glu- cose 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 gener- ally well tolerated, with the frequency of adverse events being similar to placebo and a low frequency of hypoglycemia. Sita- gliptin does not appear to alter the phar- macokinetics 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 interac- tions. 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. Index terms: Antidiabetic agents; Com- bined therapy; Diabetes mellitus; Dosage; Drug interactions; Mechanism of action; Metformin; Pharmacokinetics; Sitagliptin; Thiazolidinediones; Toxicity Am J Health-Syst Pharm. 2008; 65:521-31 T ype 2 diabetes mellitus accounts for more than 90% of all diabetes diagnoses and is characterized by insulin resistance and relative insu- lin deficiency. 1 Although numerous medications exist for the treatment of patients with type 2 diabetes mellitus, maintaining glucose ho- meostasis in these patients remains a challenge. Current therapies are as- sociated with various adverse effects such as hypoglycemia (sulfonylureas, insulin, and meglitinide), weight gain (sulfonylureas, insulin, and thiazoli- dinediones), and gastrointestinal in- tolerance (metformin, a-glucosidase inhibitors, and incretin analogues). 2,3 Sitagliptin (Januvia, Merck), which received labeling approved by the Food and Drug Administration (FDA) in October 2006, belongs to a novel class of medications with a new mechanism of action known as dipeptidyl-peptidase IV (DPP4) inhibitors and enhances the body’s ability to lower elevated blood glucose levels with minimal adverse effects. This article reviews the pharma- cology, pharmacokinetics, safety, clinical efficacy, and role in therapy of sitagliptin in the management of type 2 diabetes mellitus. Pharmacology Incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulino- tropic polypeptide (GIP), are re- leased by the intestines in response to meals and reduced in the fasting