A Critical Review of the Evidence Behind Diabetes Guidelines

A review of clinical studies cited in the American Diabetes Association guidelines
A review of clinical studies cited in the American Diabetes Association guidelines

The American Diabetes Association (ADA) 2016 guidelines on the prevention of cardiovascular disease (CVD) in diabetes provides comprehensive information to aid clinicians in the management of diabetes patients, however, a recent review of the literature has revealed "inconsistent and contradictory evidence" surrounding some of these recommendations. Findings from this review were published in the journal Diabetes Research and Clinical Practice.

While clinical practice guidelines are intended to help clinicians in disease management, these recommendations may not always be consistent across various professional organizations nor are they always evidence-based. To understand the basis for the ADA recommendations, researchers from the University of New Mexico School of Medicine, Albuquerque, NM reviewed the clinical trials that were cited in these guidelines that included "hard CVD endpoints." Studies included in the review targeted risk factors for CVD in diabetes such as glycemic and blood pressure (BP) control, lifestyle interventions, lipids reduction, and antiplatelet therapy. In addition, a literature review was conducted to identify other studies with similar endpoints that may not have been included in the ADA guidelines. 

Lifestyle interventions:

The diabetes guidelines emphasize lifestyle changes (eg, diet, weight loss, exercise), however, only two relevant studies were found that had evidence regarding the effects of lifestyle interventions (AHEAD and PREDIMED). In AHEAD, the effects of diet, weight loss, and exercise were assessed, but after a mean follow-up of 9.6 years, no clinical benefit was noted. In PREDIMED, a reduction in CV events was seen in the group with diabetes randomized to the Mediterranean diet. 

Antiplatelet therapy:

Seven randomized controlled trials were identified that included aspirin therapy for primary prevention of diabetes, however, not one study reported a mortality benefit and only one showed a reduction in CV events; the remaining studies did not report a clinical benefit. There were no randomized controlled trials to support antiplatelet therapy for secondary prevention of diabetes, however, one meta-analysis did report no significant CVD reduction in diabetes patients.

Statin therapy:

Four randomized controlled trials included results on the use of statin therapy in patients with diabetes, however, none of these studies reported a mortality benefit; most did show a reduction in CV events. The CV benefits of statins in patients with diabetes were also reported in three meta-analyses, but none of these showed a mortality benefit.

Glycemic control:

There has been evidence to suggest that drug therapy used for glycemic control may also impart long-term CVD benefits. In this review, the researchers found mixed results with regards to the effects of glycemic control on CVD outcomes. In two randomized controlled trials, where modest HbA1c reductions were seen, a reduction in mortality and CV events was noted; two other studies also showed a benefit in a composite endpoint of CV events and mortality. Four randomized controlled studies that looked at intensive glycemic control found no impact on mortality or CVD, and one study, that specifically looked at high risk diabetes patients, reported harm rather than benefit.