Glucagon-like peptide 1 receptor agonists and cardiovascular risk in type 2 diabetes: a clinical perspective

Diabetes is associated with the development of premature atherosclerotic disease, including coronary heart disease and acute coronary syndromes. A late consequence of this process is the development of chronic heart failure, which contributes to the increased cardiovascular (CV) morbidity and mortality associated with diabetes. Reduction of cholesterol with statins and intensive blood pressure control significantly reduce vascular events in people with diabetes. Intensive treatment of glycaemia reduces microvascular complications, especially retinopathy and nephropathy, but has only a modest effect in reducing macrovascular complications. Attention has therefore focused on individual antidiabetic drugs or drug classes to determine if these have effects in reducing CV events beyond the reduction of blood glucose. Glucagon-like peptide 1 (GLP-1) receptor agonists are a class of injected therapies that enhance the incretin effect, increasing insulin release from the pancreas and reducing glucagon production. They also have a central effect, increasing satiety, and in routine clinical use are associated with reductions in body weight. Another possibly beneficial effect of these drugs is a slight but significant reduction in systolic blood pressure. Data from cohort studies have indicated no increase in CV events with GLP-1 receptor agonists, and perhaps some reductions in CV events. The safety and possible CV benefit of these drugs is now being tested in large, multicentre, randomized, placebo-controlled trials.