Individualizing Targets and Tactics for High-Risk Patients With Type 2 Diabetes

Abstract

Four years ago, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was stopped early as the result of increased mortality associated with intensive glycemic treatment of a population with type 2 diabetes (T2DM) and high cardiovascular (CV) risk (1). Further reports have appeared from ACCORD (2) and other studies of high-risk populations, notably the Action in Diabetes and Vascular Disease: Preterax and Diamacron MR Controlled Evaluation (ADVANCE) (3) and the Veterans Affairs Diabetes Trial (VADT) (4). These studies provide a body of evidence that intensive treatment of hyperglycemia in T2DM does not in all cases lead to an acceptable balance of benefits to risks. Although important questions remain, both the main findings and secondary and epidemiological analyses from these studies suggest possible changes of our therapeutic approach. This article summarizes the original findings of these trials, discusses recent reports from ACCORD, and describes the authors’ experiences in implementing the intensive regimen at a major ACCORD site. It will not cover all publications on CV risk in T2DM. Rather, we aim to present an updated view of challenges and opportunities in treating high-risk patients with T2DM, drawing mainly on lessons from ACCORD and including some testable hypotheses. The opinions expressed are our own and not meant to represent those of any professional or investigative group. The UK Prospective Diabetes Study (UKPDS) (5) enrolled participants soon after diagnosis of T2DM and did not require them to have other CV risk factors. At the end of randomized comparison of intensive versus standard glycemic treatment, improvements of microvascular end points were found but not a reduction of CV events or mortality. However, the numbers of participants and the rates of CV events were relatively low and thus the statistical power was limited. Later studies were designed to test the effect of intensive …