Thirty million Americas live with type 2 diabetes mellitus (T2DM), of whom, seven million are as yet undiagnosed. Descriptions of diabetes-related symptoms have dated back to B.C., and initial antihyperglycemic therapies (insulin & metformin) were discovered in the 1920s. What has changed and why should cardiologists now be involved in T2DM care? Until recently, the therapeutic approaches to T2DM were "glucocentric" with limited strategies known to modify disease course. T2DM-focused care was nearly universally delivered by primary care physicians and/or endocrinologists. However, in the last several years, this traditional approach of T2DM care delivery has been challenged and reshaped, now mandating a multidisciplinary approach inclusive of cardiologists.

New Challenges, Targets, and Therapies in T2DM
Unfortunately, despite initial progress in prevention, there has been a resurgence of cardiovascular complications of T2DM in the US, especially among younger and middle-aged adults.¹ Despite traditional risk factor control, including adequate glycemic control, patients with T2DM face residual risks of select cardiovascular events, namely heart failure (HF).² While intensive glycemic targets may result in reductions in cardiovascular events after a decade, "legacy" effects have been recently questioned as these putative benefits do not appear to persist in long-term follow-up.³ As such, previous narrow glycemia-related therapeutic goals have expanded and now encompass opportunities to avert or delay cardiovascular events.

Until recently, targeted therapies aimed to reduce residual cardiovascular risk in this population were lacking. Stemming from an industry-wide guidance issued by the US Food and Drug Administration (FDA) in 2008 requiring all emerging antihyperglycemic therapies to undergo specific cardiovascular outcome assessment, now a decade later, we have witnessed perhaps one of the most striking increases in scientific evidence across medical disciplines. More than 20 cardiovascular outcomes trials evaluating more than 150,000 patients have been completed to date.^4,5 Two classes of antihyperglycemic therapies, sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the glucagon-like peptide-1 receptor agonists (GLP-1RA), have been demonstrated to improve atherosclerotic cardiovascular events, HF, and renal events among patients with T2DM.^6,7

Both evidence-based classes are not "novel"; the first GLP-1RA, exenatide, and the first SGLT2i, canagliflozin, were introduced in 2005 and 2013, respectively. Together with dipeptidyl peptidase-4 inhibitors, these represent the fastest growing antihyperglycemic therapies in the US.⁸ There are now four SGLT2i and six GLP-1RA approved by the FDA for their antihyperglycemic potential. In addition, specific regulatory labels for cardiovascular risk reduction have been added for 2 SGLT2i (empagliflozin & canagliflozin) and the GLP-1RA, liraglutide.

Missed Opportunities in Cardiovascular Risk Reduction
Despite their longstanding availability, increased recent use, and amounting cardiovascular evidentiary base, cardiologists appear to infrequently engage in T2DM care. In the multicenter Partners HealthCare system (Boston, MA) of >10 institutions, of the ~2,000 first prescriptions of SGLT2i from 2013-2017, cardiologists initiated <5%.⁹ Despite over a third of patients having concomitant cardiovascular disease, cardiologists similarly accounted for <5% of ~7,500 new starts of GLP-1RA from 2005-2018.¹⁰ Nationally, similar missed opportunities for use of these therapies among high-risk patients with T2DM have been described. Among 182,525 patients in the National Cardiovascular Data Registry Diabetes Collaborative Registry (NCDR DCR), use of SGLT2i was only ~5% of eligible patients between 2013-2016.¹¹ Similarly, in the US-based Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) registry, of stable patients with atherosclerotic cardiovascular disease, SGLT2i and GLP-1RA were used in only 9% and 8%, respectively, between 2016-2018.¹² Overall, only 7% of patients were on comprehensive guideline-recommended medical therapies for secondary prevention in GOULD, which was achieved relatively less frequently by patients under the predominant care of a cardiologist.¹² Beyond prescribing patterns, specialists may vary in quality of T2DM care; patients seen in endocrinology practices appear to perform better in meeting metrics of glycemic control and foot examinations, while patients seen in cardiology practices achieve better blood pressure control.¹³

Why Should Cardiologists Participate in Diabetes Care?
With obesity growing unchecked across the US, metabolic disease states are projected to increase in prevalence. With approximately 8,000 endocrinologists in the US, unevenly dispersed across states, access to specialty care may be limited in the face of this growing burden. In contrast, there are ~23,000 cardiologists in the US who may have increased points of contact with patients with T2DM. In fact, a recent experience from the Yale New Haven Health System suggested that high-risk patients with T2DM with comorbid atherosclerotic cardiovascular disease or HF interact with cardiologists on average five to eight times more often than visits with endocrinologists during a year of longitudinal care. Many at-risk patients referred to cardiologists may have undiagnosed T2DM or prediabetes providing additional avenues of prevention. Cardiologists may also interface with patients during critical junctures of cardiovascular care (such as shortly after myocardial infarction or hospitalization for HF) that may facilitate early integration of therapies. Cardiologists, regardless of degree of specialization, have long participated directly in modification of core cardiovascular risk factors (e.g. blood pressure, lipids). Risk reductions observed with SGLT2i and GLP-1RA are comparable or exceed those afforded by benefits seen with other commonly prescribed pharmacologic therapies.

Progress Towards Multidisciplinary Care Models
An important reversal in progress in reducing cardiovascular complications has been observed in the US among patients with T2DM in the last several years. For the first time, antihyperglycemic therapies are now available to modify disease course in T2DM. Antihyperglycemic therapies now represent some of the most rigorously studied therapies across cardiovascular, renal, and metabolic domains. Unfortunately, uptake of these evidence-based therapies has been sluggish, especially among patients who may benefit the most, those with established T2DM and prevalent cardiovascular disease. Paralleling paradigm shifts from "glucocentric" views to constructs centered around cardiovascular risk reduction, several innovative models of multidisciplinary care have been proposed. While professional societies worldwide attempt to ensure sufficient competence for cardiovascular clinicians in T2DM management¹⁴, few thought leaders have even called for development of a new subspecialty training pathway, "cardiometabolic medicine".¹⁵ Early integration of evidence-based therapies in T2DM has also now been supported by multi-specialty guidelines^16-22, including the American College of Cardiology, American Heart Association, Heart Failure Society of America, and European Society for Cardiology. Dedicated registries, such as the NCDR DCR, have been launched to rigorously evaluate optimal approaches to provision of high-quality multidisciplinary T2DM.²³ Regardless of strategy of T2DM care moving forward, cardiovascular specialists should be equipped with the necessary practical knowledge^24,25 to screen for diabetes, participate in risk factor modification, and introduce evidence-based antihyperglycemic therapies in clinical practice (Figure 1).

Figure 1: Evolving Role of Cardiovascular Specialists in Diabetes Care

References

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Keywords: Diabetes Mellitus, Type 2, Diabetes Mellitus, Dipeptidyl-Peptidase IV Inhibitors, Metformin, Insulin, Cholesterol, LDL, Prediabetic State, Risk Factors, Cardiovascular Diseases, American Heart Association, Blood Pressure, Secondary Prevention, Physicians, Primary Care, United States Food and Drug Administration, Lipids, Hypoglycemic Agents, Glucosides, Benzhydryl Compounds, Peptides, Obesity, Dyslipidemias, Risk Reduction Behavior, Myocardial Infarction, Heart Failure, Registries, Sodium-Glucose Transport Proteins, Hospitalization

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