Cardiologists’ role in diabetes care changing
In the past few years, there has been a flurry of new data that demonstrate CV benefits of newer diabetes drugs, particularly SGLT2 inhibitors and GLP-1 receptor agonists, with the FDA thereafter granting expanded CV indications for many of these drugs.
The SGLT2 inhibitors — canagliflozin (Invokana, Janssen), dapagliflozin (Farxiga, AstraZeneca) and empagliflozin (Jardiance, Boehringer Ingelheim) — have been shown to reduce a spectrum of CV events, particularly HF-related events and provide CV benefits, especially when it comes to the prevention of HF hospitalizations possibly mediated via hemodynamic effects, although the exact mechanisms remain undefined. Certain GLP-1 receptor agonists, including dulagutide (Trulicity, Eli Lilly), liraglutide (Victoza, Novo Nordisk), semaglutide (Ozempic, Novo Nordisk) and albiglutide (Tanzeum, GlaxoSmithKline) have demonstrated significant reduction of CV events, mostly antithrombotic, via mechanisms that also remain undefined, but do not appear to impact HF hospitalizations.
With a clearer picture today about the CV benefit of these newer glucose-lowering agents, questions remain about who should be prescribing these therapies. As rates of type 2 diabetes, in particular, continue to rise worldwide, the cardiology community continues to care for increasing number of patients with both CVD and diabetes. Moreover, the shortage of endocrinologists in the United States currently available to care for patients with diabetes further complicates this issue.
“[Diabetes] is really a part of our everyday life,” Cardiology Today Editorial Board Member Darren K. McGuire, MD, MHSc, distinguished teaching professor of internal medicine at the University of Texas Southwestern Medical Center, said in an interview. “Diabetes is so tightly linked to cardiovascular risk. Cardiologists see 10 times more patients with diabetes as do endocrinologists. It is an enriched population and ... between 20% and 30% of unselected patients in a cardiology clinic practice have diabetes. That is three times the population prevalence, and shows you the concentration of diabetes in a cardiovascular patient population. We have treated these patients for the entirety of our careers.”
Despite the new data and indications, as well as the growing number of patients with diabetes, prescription of the newer diabetes drugs remains low among cardiologists. In a recent retrospective study by Muthiah Vaduganathan, MD, MPH, a fellow in cardiovascular medicine at Brigham and Women’s Hospital Heart and Vascular Center, and colleagues, published in the Journal of the American College of Cardiology in late 2018, cardiologists at a major tertiary care center prescribed only about 5% of all SGLT2 inhibitors from 2013 to 2017, with no appreciable increase after positive data emerged from CV outcomes trials and the FDA expanded labeling for use of these agents for CV risk reduction.
However, some cardiologists do not believe they should be responsible for prescribing these newer drugs.
“On the surface, it seems a valid approach, but the cardiologist who initiates a new treatment should be responsible for managing the patient’s diabetes and adjusting other diabetic medications if needed, as was done in the outcome trials. In my daily experience and dialogue with my other cardiologists at our institution and others, none of us want to juggle with the other diabetic medications and also manage patients’ cardiovascular issues,” Udho Thadani, MD, MRCP, FRCPC, FACC, FAHA, FCCS, professor emeritus of medicine/cardiology and consultant cardiologist at University of Oklahoma Health Sciences Center and VA Medical Center in Oklahoma City and Cardiology Today Editorial Board Member, said in an interview.
A growing problem
An estimated 30.3 million people — 9.4% of the U.S. population — have diabetes, according to the CDC’s 2017 National Diabetes Statistics Report. Moreover, 7.2 million Americans have undiagnosed diabetes, and 84.1 million U.S. adults have prediabetes, which is equivalent to 33.9% of the U.S. population.
Diabetes is also the No. 7 leading cause of death in the U.S., according to a CDC National Center for Health Statistics Data Brief published in 2018.
“Cardiologists are an integral part of taking care of patients with diabetes,” Mikhail Kosiborod, MD, FACC, FAHA, cardiologist at Saint Luke’s Mid America Heart Institute and professor of medicine at the University of Missouri-Kansas City School of Medicine, told Cardiology Today. “We know that people with diabetes, especially those with diabetes and cardiovascular disease, are much more likely to see a cardiologist than an endocrinologist, and at least as likely to see a cardiologist as a primary care doctor. Every ‘touch’ that a cardiologist has with a patient with type 2 diabetes — meaning every encounter, every office visit, every hospitalization — is an opportunity to improve care and reduce the risk for morbid events.”
One factor that can potentially change how cardiologists care for patients with diabetes is education, not only for the cardiologists themselves, but for the physicians to teach their patients how diabetes can be a powerful risk factor for those with high CV risk or who already have CVD.
Patients with CVD or high CV risk have “at least two to three times greater risk of having another event as compared to those who do not have diabetes,” Prakash C. Deedwania, MD, FACC, FACP, FAHA, professor of medicine and director of cardiovascular research at the University of California, San Francisco School of Medicine, told Cardiology Today. “That is a very powerful point for cardiologists.”
Hesitation in prescribing
Current prescription patterns of the newer SGLT2 inhibitors and GLP-1 agonists do not reflect the role of cardiologists in the care of patients with diabetes (Figure).
“Prescription of therapies for diabetes has traditionally been under the purview of primary care physicians and endocrinologists,” Vaduganathan said in an interview. “There’s certainly some inertia carried over from this previous traditional landscape.”
With the newer data and expanded indications for the SGLT2 inhibitors and GLP-1 agonists, the uptake in prescription is not as quick as some anticipated.
“That’s a question of a practice-changing pattern,” Deedwania said. “It will happen, but it has not happened as quickly as one would have expected it. Only in the last 2 to 2.5 years we have seen this evidence. Having been in practice for 40 years, I have seen these [practices] not being adopted as quickly as people in academics or industry would like.”
Generally, the role of cardiologists in the CV care of patients with diabetes focuses less on glucose lowering and more on other passive diabetes related interventions such as lipid lowering and antiplatelet therapy. Regardless, both the CV and glucose-lowering aspects of diabetes should be considered during care, especially when prescribing medications, experts told Cardiology Today.
“This is a new paradigm of saying we need to be mindful of the choice of glucose-lowering agents not just because of potential cardiovascular harm, but also — and increasingly so — because some of these can have profound cardiovascular benefits, which have little to do with their glucose-lowering properties,” Kosiborod said.
The ever-changing landscape of diabetes treatment is another obstacle that may potentially prevent cardiologists from prescribing these agents, experts said.
“To expect cardiologists to also manage patients’ diabetes as well as their cardiovascular problems is too much to ask,” Thadani told Cardiology Today. “Current workload and mandated coding requirements on which reimbursement is based will require that the physician coding for a ‘primary’ condition must deal with managing the condition, including reconciling the medications. This is not practical or possible in the current regulatory environment.”
Hesitation in the cardiology community to prescribe these agents may also relate to adverse events, particularly with SGLT2 inhibitors. Side effects with SGLT2 inhibitors include polyuria, mycotic genitourinary infections and there is a possibility that one of the agents in the class (canagliflozin), as shown in the CANVAS program, may increase the risk for amputations, although this was not confirmed in the latest outcome trial of this drug (CREDENCE). A case series just published in Annals of Internal Medicine in May suggested a possible safety concern of Fournier gangrene, which is a rare urological emergency that is characterized by necrotizing infection of the external genitalia, perineum and perianal regions, although this risk has not been seen in clinical trials. Factors that may make cardiologists uncertain about prescribing and administering GLP-1 receptor agonists include their injectable route of administration and requirement for dose titration.
“Cardiologists can no longer ignore the potential benefit of these drugs in patients with diabetes, but taking that next step in being able to use these drugs effectively and taking into consideration the dosing and ultimately the potential adverse effects is something that many cardiologists are not really appropriately ready for and unwilling to move to the next space,” Robert H. Eckel, MD, professor of medicine in the division of endocrinology, metabolism, diabetes and cardiology; professor of physiology and biophysics; Charles A. Boettcher II Chair in Atherosclerosis at the University of Colorado Denver Anschutz Medical Center; director of the lipid clinic at University of Colorado Hospital in Aurora; and past president of the American Heart Association, told Cardiology Today.
Although this paradigm shift in the cardiologist’s role in the care of this patient population may be relatively new, some cardiologists feel that this should have always been the case.
The care of patients with diabetes and CVD, or risk for CV, could shift to include cardiologists playing an important role in prescribing SGLT2 inhibitors and GLP-1 receptor agonists.
“The initial prescription of these agents and the initial management of these patients with these two classes of therapies can largely be done and guided by the cardiologist alone,” Vaduganathan said. “Certainly, there are going to be some patients that have complex diabetes therapies that require complex insulin titration for which endocrinologists should guide management. However, the access to endocrinologists is becoming increasingly limited, especially in certain states in the U.S. As such, reliance on a single specialty to guide all diabetes management is impractical.”
However, he noted, cardiologists “have not been trained to and would likely feel uncomfortable with complex insulin titration or in the longitudinal management of type 1 diabetes.”
In addition to administering the newer diabetes drugs, cardiologists should consider other tactics to reduce CV risk in patients with diabetes such as LDL lowering and BP control.
“This is yet another important part of the critical process to make sure that people who can benefit from treatments have a chance of receiving those treatments,” Kosiborod said. “Arguably, this is no different and complementary to all the other aspects of cardiovascular risk reduction like lipids, blood pressure, exercise, weight reduction, smoking cessation and all of the other interventions that are effective in lowering the risk.”
However, “just because the disease has cardiovascular complications does not mean a cardiologist should supervise diabetic care,” Thadani said.
“In my opinion it should not be a turf battle. We must keep patient’s welfare in mind at all times,” he told Cardiology Today. “Primary care providers and endocrinologists are the ones who should consider prescribing the newer drugs as they see fit, while taking into consideration the positive effects on cardiovascular outcomes with these novel agents.”
Greater education for cardiologists on SGLT2 inhibitors and GLP-1 receptor agonists, specifically how to prescribe, follow up and monitor patients for potential side effects is warranted.
In November 2018, the AHA, the American Diabetes Association and industry leaders launched the Know Diabetes by Heart initiative for clinicians, providers, patients and communities to raise awareness about the increased risk for CVD in patients with type 2 diabetes.
The ACC also collaborated with the ADA in the preparation of an expert consensus decision pathway on novel therapies for CV risk reduction in patients with atherosclerotic CVD and type 2 diabetes, which was published in the Journal of the American College of Cardiology in November 2018.
“More efforts that have been made by organizations in general including the American College of Cardiology should help clinicians get on board,” Deedwania told Cardiology Today.
Additional education opportunities that focus on the care of patients with diabetes by a cardiologist are available at conferences such as the Cardiometabolic Health Congress and Heart in Diabetes. In addition, publications are making more of an active effort to recruit more papers related to both cardiology and diabetes, McGuire, who is also the deputy editor for Circulation, said.
Larger meetings have added more cardiometabolic and diabetes tracks to their programs and have included late-breaking clinical trials focused on CV outcomes in patients with diabetes, such as the DECLARE-TIMI 58 trial presented at the AHA Scientific Sessions in November.
Improvements in the platforms clinicians use could also allow for more integrated care and easier communication between primary care physicians, cardiologists and endocrinologists. Some clinics and institutions already make efforts to apply this to their integrated electronic medical records independent of sending the clinic notes to the primary care provider, McGuire said.
Eckel and Michael J. Blaha, MD, MPH, associate professor of medicine at Johns Hopkins University School of Medicine and Cardiology Today Next Gen Innovator, wrote a paper published in The American Journal of Medicine in March that details a proposal to develop cardiometabolic medicine as a new medical subspecialty.
“Rather than shunting patients back and forth between cardiologist, endocrinologist and primary care physician — with uncertain ‘ownership’ of different aspects of the patient’s care — the cardiometabolic specialist will be sufficiently trained in internal medicine, preventive cardiology and endocrinology with a practice designed to be the medical home for patients with cardiometabolic disease and atherosclerotic cardiovascular disease,” Eckel and Blaha wrote.
Saint Luke’s Mid America Heart Institute has pursued a different model: a Cardiometabolic Center of Excellence. The center emphasizes a holistic, comprehensive risk reduction approach for patients, the majority of whom have both type 2 diabetes and established CV complications.
It is through this team approach that cardiologists can help patients with diabetes get the care they need while reducing their CV risk, especially as cardiologists become more acclimated with prescribing SGLT2 inhibitors and GLP-1 receptor agonists.
“Cardiologists can only go so far in taking care of diabetes,” Eckel said. “Endocrinologists or metabolic physicians can only go so far in taking care of complications of cardiovascular disease such as cardiac arrhythmias or heart failure. What we need is a team approach right now until the cardiologist gets more educated and more comfortable with taking care of these patients. A certified diabetes educator would be a catalyst to get cardiologists more involved.” – by Darlene Dobkowski
- Bersoff-Matcha SJ, et al. Ann Intern Med. 2019;doi:10.7326/M19-0085.
- CDC. National Diabetes Statistics Report, 2017. Available at: www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf.
- Eckel RH, et al. Am J Med. 2019;doi:10.1016/j.amjmed.2019.02.027.
- Hernandez AF, et al. Lancet. 2018;doi:10.1016/S0140-6736(18)32261-X.
- Marso SP, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1607141.
- Marso SP, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1603827.
- Murphy SL, et al. NCHS Data Brief. 2018;328:1-8.
- Neal B, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1611925.
- Vaduganathan M, et al. J Am Coll Cardiol. 2018;doi:10.1016/j.jacc.2018.08.2202.
- Vaduganathan M, et al. J Am Coll Cardiol. 2019;doi:10.1016/j.jacc.2019.01.029.
- Wiviott SD, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1812389.
- Zinman B, et al. N Engl J Med. 2015;doi:10.1056/NEJMoa1504720.
- For more information:
- Prakash C. Deedwania, MD, FACC, FACP, FAHA, can be reached at firstname.lastname@example.org.
- Robert H. Eckel, MD, can be reached at email@example.com; Twitter: @robertheckel.
- Mikhail Kosiborod, MD, FACC, FAHA, can be reached at firstname.lastname@example.org.
- Darren K. McGuire, MD, MHSc, can be reached at email@example.com.
- Udho Thadani, MD, MRCP, FRCPC, FACC, FAHA, FCCS, can be reached firstname.lastname@example.org.
- Muthiah Vaduganathan, MD, MPH, can be reached at email@example.com; Twitter: @mvaduganathan.
Disclosures: Deedwania reports he received a research grant from Boehringer Ingelheim to study newer antidiabetic drugs. Eckel reports he has a financial relationship with Sanofi Regeneron, serves on a scientific advisory board for Kowa for the PROMINENT trial and serves on an advisory board for Merck and Novo Nordisk. Kosiborod reports he received a research grant from AstraZeneca and Boehringer Ingelheim; serves as a consultant or on an advisory board for Amarin, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, GlaxoSmithKline, Glytec, Intarcia, Janssen, Merck, Novartis, Novo Nordisk and Sanofi; and received other research support from AstraZeneca. McGuire reports he served as clinical trial leadership for AstraZeneca, Boehringer Ingelheim, Eisai, Esperion, GlaxoSmithKline, Janssen, Lexicon, Lilly USA, Merck, Novo Nordisk and Sanofi Aventis and consulted for Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Lilly USA, Merck, Metavant, Novo Nordisk and Sanofi Aventis. Thadani reports his institutions received research support from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo/Lilly, Gilead Sciences, Johnson and Johnson, NIH, Pfizer, Sanofi and VA Co-Op studies; he consults for Gilead Sciences, MP4 Pharmaceuticals, Servier and The Medicines Company; and spoke for Amgen, Daiichi Sankyo/Lilly and Gilead Sciences. Vaduganathan reports he received funding support from the NIH and served on advisory boards for Amgen, AstraZeneca, Baxter Healthcare and Bayer.