Duke Study to Examine How Diabetes, Cardiovascular Guidelines Get Into Clinical Practice

Physicians who treat people with type 2 diabetes (T2D) have more treatment choices than ever, but the question of how quickly the latest scientific findings make their way into clinical practice is one that has troubled leading endocrinologists and cardiologists for some time.

In fact, the 2019 Standards of Medical Care in Diabetes, the annual guidelines update from the American Diabetes Association, specifically discusses the challenge of “therapeutic inertia,” which happens when physicians either don’t change a patient’s diabetes regimen to newer, more appropriate, therapies or combinations, or don’t adjust doses if the current regimen fails to produce the desired glycemic target.

For more than a year, the ADA and the American College of Cardiology (ACC) have collaborated closely on recommendations for patients who have T2D and atherosclerotic cardiovascular disease (ASCVD) or heart failure, reflecting clinical findings of the past few years that show some drugs in newer therapy classes not only help patients safely achieve glycated hemoglobin (A1C) targets, but can also bring cardiovascular benefits, including reduced risk of hospitalization for heart failure and cardiovascular death. These findings were included in both the ADA 2018 Standards of Medical Care in Diabetes and the ACC Expert Consensus Decision Pathway on novel therapies for cardiovascular risk reduction in adults with T2D and ASCVD.

Now, a new study will examine how to best get these recommendations from expert committees and journal articles and into clinics where they can help patients.

The Duke Clinical Research Institute will lead a research program, COORDINATE-Diabetes (COOrdinating CaRDIology CliNics RAndomized Trial of Interventions to Improve OutcomEs), which will be funded by Boehringer Ingelheim and Eli Lilly and Company. The companies are the makers of the sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin (Jardiance), which in 2015 became the first T2D therapy shown to have a cardiovascular benefit in the EMPA REG OUTCOME trial.

Thomas Seck, MD, vice president of US Clinical Development and Medical Affairs, Primary Care, at Boehringer Ingelheim, said the partnership with Duke will try to unravel some longstanding disconnects between what’s happening in research and what happens in primary care, where the vast majority of diabetes care takes place. “There’s a problem in the primary care space,” he said. “How do we translate innovation into clinical practice?”

“Few rigorous studies have tested the effectiveness of a multidisciplinary approach to improving care among this vulnerable patient population,” noted Sherry Martin, MD, vice president, Medical Affairs, Lilly, said in a statement. “Given the serious cardiovascular complications associated with type 2 diabetes, it is important for cardiologists and endocrinologists to work collaboratively to help improve care for people with type 2 diabetes and cardiovascular disease.”

It’s well known that cardiovascular disease is the leading cause of death and disability for people with diabetes, and after years of improvement in care, it appears things are getting worse. A recent study showed that amputations among people with diabetes were on the rise again after years of decline. People with diabetes are up to 4 times more likely to develop cardiovascular disease than those without the disease, yet a study published last month in the Journal of the American College of Cardiology found that cardiologists were not very likely to prescribe SGLT2 inhibitors, although they did shift to empagliflozin after publication of the EMPA REG OUTCOME results.

SGLT2 inhibitors, taken once daily by mouth, and glucagon-like peptide-1 (GLP-1) receptor agonists, injectables given once daily or once weekly (although a pill form is being studied) both have been shown to offer some weight loss benefits; the results are more pronounced for GLP-1 receptor agonists. Many see the GLP-1 class in particular as underutilized, given the benefits. By contrast, insulin is associated with weight gain, and cost increases have caused some patients to ration supplies or skip doses. In fact, the 2019 Standards of Care for the first time recommends GLP-1 receptor agonists as the go-to injectable before insulin.

The COORDINATE-Diabetes trial will reach 46 cardiology clinics across the United States and aims to enroll 30 patients at each site. Randomization will be by clinic—patients at the sites will be staffed by physicians who have had either basic education or an intensive intervention, where the physicians will have coordinated care between cardiologists and endocrinologists who will be charged with developing a multidisciplinary care pathway).

Specifically, teams at the intervention sties will be tasked with reaching each patient’s primary care physician to ensure they understand how to use the guideline-recommended therapies.

Results will measure how well the intervention affects the sites’ use of guideline-recommended therapies after 12 months.

Seck said the trial will look at questions such as how well intervention arm clinics adhere to current guidelines, how well coordination between the endocrinologists and cardiologists allows for coordination of care for multiple complications, and how well diabetes therapies are integrated with other medications, such as statins for cholesterol.

Do health plans have a role in the study?

“Health plans and payers will have an interest in the results,” Seck said, although they will not be directly involved in the study.

Payers have likely affected uptake of novel T2D therapies. Since 2013, when the first SGLT2 inhibitor, canagliflozin (Invokana/Janssen) was approved, major US formularies and pharmacy benefit managers have shifted their preferences for various novel T2D therapies, and this can affect whether physicians prescribe them or whether patients are willing to use them.

More recently, the SGLT2 inhibitors empagliflozin and canagliflozin have received cardiovascular indications from FDA; in addiction the GLP-1 receptor agonist liraglutide has an FDA indication for reduction of cardiovascular event risk. ACC listed empagliflozin as the preferred SGLT2 inhibitor and liraglutide as the preferred GLP-1 receptor agonist in the new consensus pathway.