They say timing is everything, and what better time to have a registry focused on type 2 diabetes mellitus (T2DM)? Here are four important reasons:

1. To better understand the changing epidemiology of T2DM, prevalent in patients with an array of cardiovascular disorders including hypertension, coronary artery disease, peripheral vascular disease, congestive heart failure, and stroke.
2. To better understand the metabolic syndrome associated with T2DM and its relationship to cardiac and vascular disease beyond measures directed at glycemic control.
3. To set the stage for gauging the impact of recently published randomized clinical trials showing clear cardiovascular protection with the use of specific diabetic therapies.
4. To identify trends in the comprehensive care of patients with T2DM that include treatments of lipids, hypertension, and obesity, and approaches to the treatment of hemodynamically significant coronary and vascular disease and identify treatment gaps.

Cardiologists have been very proactive and comfortable in treating most of the cardiometabolic contributors associated with T2DM. Yet data from the PINNACLE Registry reveal persistent gaps in the treatment of lipids in T2DM patients, with nearly 30 percent not treated with a statin.¹

However, cardiologists are much less assertive when it comes to initiating or modifying glycemic treatments. This is likely to change now that we have entered a new era based on three important randomized trials that evaluated the effect of the sodium glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin and the glucagon-like peptide-1 receptor agonists (GLP-1 RA) liraglutide and semaglutide.^2-4 These three compounds reduced cardiovascular events in diabetic patients with established cardiovascular disease.

In the EMPA-REG OUTCOME trial, empagliflozin reduced the incidence of the composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke by 14 percent (p = 0.04 for superiority).² Death from cardiovascular causes was reduced by 38 percent and heart failure hospitalizations by 35 percent. There was a favorable trend for a reduction in nonfatal myocardial infarction but an unfavorable trend for nonfatal stroke.

The primary composite outcome in SUSTAIN-6 that evaluated semaglutide, the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, was reduced by 26 percent over placebo (p = 0.02 for superiority).³ Nonfatal stroke was significantly reduced by 39 percent (p = 0.04), with a strong trend towards a reduction of nonfatal myocardial infarction.

In the LEADER trial involving liraglutide, there was a 13 percent (p = 0.01 for superiority) reduction of the composite endpoint of the first occurrence of death from cardiovascular causes, nonfatal (including silent) myocardial infarction, or nonfatal stroke.⁴ Death from cardiovascular causes was reduced by 22 percent (p = 0.007); the other components of the composite endpoint trended in the same direction.

The results of these well-designed, blinded, randomized clinical trials show medical interventions in diabetic patients with cardiovascular disease have protective effects. But these trials ask as many questions as they answer, including:

1. Why is cardiovascular protection not seen with other classes of glucose-lowering drugs?
2. Why did the SGLT-2 inhibitors and GLP-1 RA evaluated in these clinical trials exert a protective effect? Was it based on reduction in weight or caloric intake, diuretic effects, or other effects on metabolism?
3. Is hyperglycemia the primary culprit in the development of cardiovascular (macrovascular) complications of T2DM?

The Diabetes Collaborative Registry (DCR) has been designed to answer these questions and to track and improve the quality of care of diabetes and metabolic syndrome across the continuum of primary and specialty care. The participation of primary care physicians, endocrinologists, cardiologists, and other healthcare providers managing diabetes is encouraged. The registry is a partnership of the ACC, American Diabetes Association, American College of Physicians, American Association of Clinical Endocrinologists, and Joslin Diabetes Center.

The DCR aims to measure adherence to clinical guidelines, quantify local performance, and report these data with national benchmarks to allow for rapid-cycle quality improvement efforts. Research efforts within the DCR may allow for an enhanced understanding of disease progression, generate new insights into management patterns, and highlight opportunities for care improvement.⁵

References

1. Pokharel Y, Gosch K, Nambi V, et al. J Am Coll Cardiol 2016;68:1368-9.
2. Zinman B, Wanner C, Lachin JM, et al. N Engl J Med 2015;373:2117-28.
3. Marso SP, Daniels GH, Brown-Frandsen K, et al. N Engl J Med 2016;375:311-22.
4. Marso SP, Bain SC, Consoli A, et al. N Engl J Med 2016;375:1834-44.
5. Arnold SV, Inzucchi SE, McGuire DK, et al. Diabetes Care 2016;39:e99-e101.

Keywords: ACC Publications, Cardiology Magazine, Benchmarking, Benzhydryl Compounds, Coronary Artery Disease, Diabetes Mellitus, Type 2, Glucose, Glucosides, Heart Failure, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperglycemia, Hypertension, Metabolic Syndrome, Myocardial Infarction, Obesity, Peripheral Vascular Diseases, Quality Improvement, Registries, Sodium, Stroke, Symporters, United States