Recent Diabetes Trials and Their Implications on Clinical Practice

REVIEW ARTICLE


Marcus Campbell^1, Donna Leverone^2, Benjamin Epstein^2,3 and James Taylor⁴

Affiliations: ¹Clinical Pharmacology Services, Tampa, Florida, USA; ²Departments of Pharmacotherapy and Translational Research and Medicine, University of Florida, Gainesville, Florida, USA; ³East Coast Institute for Research, Jacksonville, Florida, USA and ⁴Department of Pharmacotherapy and Translational Research, University of Florida, Gainesville, Florida, USA

ABSTRACT

Patients with type 2 diabetes are at increased risk for various microvascular and macrovascular complications. The United Kingdom Prospective Diabetes Study (UKPDS) trial clearly demonstrated that reducing A1C resulted in a significant reduction in microvascular disease in patients with type 2 diabetes. Historically, there has been little evidence to indicate that reductions in A1C also reduce macrovascular events. Recent trials have attempted to answer this question and to address whether more stringent A1C goals would be beneficial in managing patients with type 2 diabetes. The Action to Control Cardiovascular Risk in Diabetes (ACCORD), the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), the Veterans Affairs Diabetes Trial (VADT), and UKPDS follow-up studies all provide some insight into these controversies, although their results are somewhat contradictory. The ADVANCE and VADT trials showed no statistically significant benefit of intensive glucose control on reduction of macrovascular endpoints. In the ACCORD trial, intensive therapy decreased the rate of nonfatal myocardial infarction but increased the rate of death from cardiovascular causes and death from any cause. The UKPDS follow-up study did show significant reductions in some macrovascular and other diabetes-related endpoints, despite loss of glycemic control differences between groups during the follow-up study. This manuscript compares these trials and their clinical implications in managing patients with type 2 diabetes.

Keywords: diabetes, ACCORD, ADVANCE, VADT, UKPDS

Correspondence: James Taylor, Department of Pharmacotherapy and Translational Research, University of Florida, PO Box 100486, Gainesville, FL 32610, USA. Tel: +1 352 273 6239; Fax: +1 352 273 6242; e-mail: jtaylor@cop.ufl.edu