Spotlight on cardiovascular risk

Several recent studies addressed the effects of diabetes and diabetes treatments on cardiovascular risk.

Two manufacturer-sponsored studies, published by the New England Journal of Medicine on Sept. 2, analyzed dipeptidyl peptidase 4 inhibitors (DPP-4) in patients with type 2 diabetes and cardiovascular risk factors. In the first study, 5,380 patients who had either an acute myocardial infarction (MI) or hospitalization for unstable angina in the preceding three months were randomized to either alogliptin or placebo and followed for up to 40 months. Although alogliptin significantly lowered glycated hemoglobin (7.70% vs. 8.06% for placebo), the treated and placebo groups had similar rates of death from cardiovascular causes, nonfatal MI or nonfatal stroke (11.3% vs. 11.8%; hazard ratio, 0.96).

In the second study, more than 16,000 type 2 diabetes patients with a history or increased risk of cardiovascular events were randomized to saxagliptin or placebo and followed for a median of 2.1 years. Both groups had similar rates of cardiovascular death, MI or ischemic stroke (7.3% with saxagliptin vs. 7.2% with placebo). However, significantly more saxagliptin patients were hospitalized for heart failure (3.5% vs. 2.8%; hazard ratio [HR], 1.27), a finding that researchers described as unexpected and requiring confirmation. The results also show the need for other approaches to reduce cardiovascular risk in diabetic patients, the authors said.

An accompanying editorial agreed, noting that these studies, and the current evidence generally, show that clinicians shouldn't use glycated hemoglobin levels as a predictor of cardiovascular risk or rely on antidiabetic therapies as preventive treatment for cardiovascular events, but rather aggressively manage standard cardiovascular risk factors.

Another study, published by the Journal of the American Medical Association on Aug. 28, did offer a potential future method for predicting cardiovascular risk in patients with type 2 diabetes. An analysis of data from several large studies, including the Nurses' Health Study and the Health Professionals Follow-up Study, identified a gene associated with development of coronary heart disease (CHD) in type 2 diabetes patients. Diabetics who had a variant on chromosome 1q25 had a significantly increased risk of CHD compared to those without the variant. No such association was seen in people without diabetes, leading study authors to conclude that there is an interaction between the gene and diabetes, which could be functionally related to glutamic acid metabolism.