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

1. To better understand the changing epidemiology of T2DM, which is prevalent in patients who present 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 the T2DM disease state and its relationship to cardiac and vascular disease above and beyond measures directed at glycemic control.
3. To set the stage for gauging the impact of recently published randomized clinical trials finally showing clear cardiovascular protection with the use of specific diabetic therapies.
4. To be able 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 recently published data from the PINNACLE Registry, another important source of clinical data, has shown persistent gaps in the treatment of lipids in patients with T2DM with nearly 30% of not treated with a statin.¹ The PINNACLE Registry is cardiology's largest outpatient quality improvement registry, capturing data on coronary artery disease, hypertension, heart failure, and atrial fibrillation and has played a key role in identifying treatment gaps in these disease states.

As a group however, cardiologists are much less assertive when it comes to initiating or modifying glycemic treatments. This is likely to change as we have now entered a new era based on three important randomized trials evaluating 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 have been found to reduce cardiovascular events in diabetic patients with established cardiovascular disease.

In the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial, empagliflozin was found to reduce the incidence of the composite endpoint of death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke by 14% (p = 0.04 for superiority).² Of the components of the primary endpoint, deaths from cardiovascular causes were reduced by 38% along with a 35% reduction in heart failure hospitalizations with favorable trends for nonfatal myocardial infarction and non-favorable trend for nonfatal stroke.

The primary composite outcome in SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Patients with Type 2 Diabetes) evaluating semaglutide, the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke was reduced by 26% over placebo (p = 0.02 for superiority).³ Non-fatal stroke was the component of that composite endpoint that was significantly reduced by 39% (p =0 .04) with a strong trend towards a reduction of non-fatal MI.

In the LEADER (Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes) trial involving liraglutide, there was a 13% (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% (p = 0.007) with the other components of the composite endpoint trending in the same direction.

The results of these trials are comforting knowing that we have quality data from well-designed randomized and blinded clinical trials showing medical interventions in diabetic patients with cardiovascular disease have protective positive effects. But these trials ask as many questions as they answer, including:

1. Why do we not see cardiovascular protection with other classes of pharmacologic agents prescribed for T2DM that lower glucose levels?
2. Why did the SGLT-2 inhibitors and GLP-1 RA evaluated in the clinical trials mentioned above exert a protective effect? Was it based on weight reduction, reduction of caloric intake, diuretic effects, or other effects on metabolism?
3. Is hyperglycemia the primary culprit in the development of cardiovascular (macrovascular) complications of T2DM?

This is why the Diabetes Collaborative Registry (DCA) is so important at this particular time. A partnership of the American College of Cardiology (ACC) with the American Diabetes Association, American College of Physicians, American Association of Clinical Endocrinologists, and Joslin Diabetes Center, the DCA is the first worldwide collaborative diabetes registry that is designed to track and improve the quality of care of diabetes and metabolic syndrome across the continuum of primary and specialty care and encourages the participation of primary care physicians, endocrinologists, cardiologists, and other healthcare providers managing diabetes. Arnold et al. in their publication, "Evaluating the Quality of Comprehensive Cardiometabolic Care for Patients With Type 2 Diabetes in the US: The Diabetes Collaborative Registry" review the role of the DCA in improving care patients with T2DM define the goals of this effort. They define the role of the DCR "to fill this void through collecting data on a national level, allowing for regular feedback and benchmarking that we envision will result in rapid-cycle quality improvement efforts. Through measuring adherence to clinical guidelines, quantifying local performance, and reporting these data with national benchmarks." In addition, "beyond local quality 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

We have high expectations for this registry and hope it equips and motivates cardiologists to partner with endocrinologists and other diabetic specialists to effect a wider breadth of the metabolic syndrome including not only hypertension and dyslipidemia but also to include glycemic control.

Interested primary care providers and specialists can find out more about the DCR, including how to enroll their practices at: https://www.ncdr.com/WebNCDR/Diabetes/publicpage.

References

1. Pokharel Y, Gosch K, Nambi V, et al. Practice-level variation in statin use among patients with diabetes: insights from the PINNACLE registry. J Am Coll Cardiol 2016;68:1368-9.
2. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28.
3. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311-22.
4. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375:1834-44.
5. Arnold SV, Inzucchi SE, McGuire DK, et al. Evaluating the quality of comprehensive cardiometabolic care for patients with type 2 diabetes in the U.S.: the Diabetes Collaborative Registry. Diabetes Care 2016;39:e99-101.

Keywords: Metabolic Syndrome, Dyslipidemias, Secondary Prevention

< Back to Listings