Strategies for optimizing glycemic control and cardiovascular prognosis in patients with type 2 diabetes mellitus

Abstract

Type 2 diabetes mellitus (DM) is a major cardiovascular (CV) risk factor and, as such, is considered a coronary artery disease risk equivalent. Although glycemic control is associated with decreased CV events epidemiologically, many prospective clinical trials have failed to conclusively demonstrate that aggressive glycemic control improves the CV prognosis of patients with type 2 DM, especially those with long-standing DM. Many therapies for type 2 DM with widely divergent mechanisms of action are available. Some of these drugs, in addition to their glucose-lowering actions, have properties that may reduce or increase CV events. Agents that lower both insulin resistance and postprandial hyperglycemia while at the same time avoiding hypoglycemia may be beneficial for CV health. This article reviews the evidence regarding the use of these agents and appropriate glycemic control targets for improving the adverse CV prognosis associated with type 2 DM. We conducted a systematic review of English articles using MEDLINE and the Cochrane Controlled Trials Register (1970-2010) using the following search terms: cardiovascular disease, randomized trials, hypoglycemia, and insulin resistance.

FIGURE 1.

Age-adjusted relative risks for cardiovascular events by glycated hemoglobin category from the European Prospective Investigation into Cancer in Norfolk study.

FIGURE 2.

Kaplan-Meier plot for any type 2 diabetes–related death with metformin and conventional therapy in the UK Prospective Diabetes Study. Adapted from Lancet, with permission from Elsevier.

FIGURE 3.

Postchallenge glucose and coronary atherosclerosis progression. Only women with postchallenge glucose values of less than 87 mg/dL (to convert to mmol/L, multiply by 0.0555) had regression in coronary atherosclerosis. From J Am Coll Cardiol, with permission from Elsevier.

FIGURE 4.

Cardiovascular (CV) events in STOP-NIDDM (STOP Noninsulin-Dependent Diabetes Mellitus). Probability of remaining free of CV disease (chronic heart disease, CV death, heart failure, cerebrovascular event, and peripheral vascular disease) from STOP-NIDDM. From JAMA, with permission. Copyright © 2003 American Medical Association. All rights reserved.

FIGURE 5.

Main secondary end point of Prospective Pioglitazone Clinical Trial In Macrovascular Events. Kaplan-Meier plot of time to death from any cause, nonfatal myocardial infarction, or stroke. CI = confidence interval; HR = hazard ratio. From Lancet, with permission from Elsevier.