D iabetes mellitus currently affects more than 220 million people world- wide. 1 The prevalence of this chronic disease is expected to double by the year 2030, due mainly to the rapid increase in obesity and physical inactivity. 1,2 Al- though there is good evidence that a large proportion of cases of diabetes and its complications can be prevented by a healthy diet, regular physical activity, maintaining a normal body weight, and avoiding tobacco, this evidence is not widely implemented. 1,2 Since many pa- tients do not follow recommendations for lifestyle modification, drug therapy is usually required to meet therapeutic goals and prevent long-term complica- tions associated with diabetes. Cardiovascular disorders such as heart disease, stroke, and hypertension frequent- ly occur in patients with diabetes. Accord- ing to the findings of several large-scale clinical studies, postprandial hyper- glycemia was found to be an independent risk factor for arteriosclerosis and cardio- vascular complications. 3,4 Additionally, the Study To Prevent Non-Insulin Dependent Diabetes Mellitus (STOP-NIDDM) trial demonstrated that improvement in post- prandial hyperglycemia delayed the onset of cardiovascular events, limited the pro- gression of diabetes, and prevented the on- set of macrovascular diseases. 5 In light of these studies, it would seem essential that the therapeutic management of di- abetes should target postprandial hyperglycemia. This article reviews publications regarding the rapid-act- ing, non-sulfonylurea agent mitiglinide to determine its po- tential place in therapy for patients with type 2 diabetes. Mitiglinide calcium hydrate is a benzylsuccinic acid derivative rapid-acting insulin secretion–stimulating agent developed by Kissei Pharmaceutical Co. Ltd. for the treat- Mitiglinide: A Novel Agent for the Treatment of Type 2 Diabetes Mellitus Haley M Phillippe and Kurt A Wargo New Drug Developments Author information provided at end of text. The Annals of Pharmacotherapy ■ 2010 October, Volume 44 ■ theannals.com OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, and safety of mitiglinide, a rapid-acting insulin secretion-stimulating agent to determine its potential role in therapy for the treatment of type 2 diabetes mellitus. DATA SOURCES: A MEDLINE search (1966–May 2010) was conducted for English-language, human studies using the terms mitiglinide, KAD 1229, S 21403, and meglitinide analogs. Abstracts presented at the American Association and European Association for the Study of Diabetes annual meetings from 2005 to 2009 were also evaluated for relevant data. STUDY SELECTION AND DATA EXTRACTION: Articles pertinent to the pharmacology, pharmacokinetics, efficacy, and safety of mitiglinide were reviewed. DATA SYNTHESIS: Mitiglinide has been shown through small clinical studies (N <400) to modestly decrease hemoglobin A 1c , postprandial hyperglycemia, and oxidative stress and inflammatory markers associated with postprandial hyperglycemia. Mitiglinide exerts its hypoglycemic activity by closing adenosine triphosphate (ATP)–sensitive potassium channels in the β-islet cells of the pancreas. This agent has a rapid onset and short duration of action, mimicking a physiologic pattern of insulin release in nondiabetic people. Studies suggest a starting dose of 5 mg 3 times daily with meals and a maximum dose of 20 mg 3 times daily. Overall, mitiglinide is well tolerated, with the most common adverse effect being hypoglycemia. CONCLUSIONS: Mitiglinide is the third agent in the class of meglitinides that targets postprandial hyperglycemia. Because of a more intensive dosing regimen, potential cost, and lack of studies assessing the clinical impact of mitiglinide therapy on oxidative stress and inflammatory markers secondary to postprandial hyperglycemia, we cannot recommend this therapy over currently approved therapies. KEY WORDS: diabetes mellitus, meglitinide, mitiglinide. Ann Pharmacother 2010;44:xxxx. Published Online, 14 Sept 2010, theannals.com, DOI 10.1345/aph.1P136 THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL ACTIVITY NUMBER: 407-000-10-025-H01-P ARTICLES