In diabetes with CVD, traditional risk factor modification remains top priority

Issue: August 2018

Jane E.B. Reusch

PHILADELPHIA — Studies demonstrating the dual efficacy of antihyperglycemic agents on both glucose and cardiovascular disease risk should change the treatment landscape only in people with high CV risk or established disease, according to a speaker here.

In the United States, 1 in 4 health care dollars are spent to treat diabetes, and with $327 billion invested in treatment annually, the disease epidemic continues to grow, Jane E.B. Reusch, MD, professor of medicine and associate director of the Center for Women’s Health Research at the University of Colorado Anschutz Medical Campus, and president of medicine and science for the American Diabetes Association, said during a presentation at the second annual Heart in Diabetes Clinical Education Conference.

For the approximately 20% of people with diabetes and established CVD, providers carefully must co-manage CV and heart failure risk in the context of diabetes, considering age, background and life expectancy, as well as new agents shown to provide CV benefit, Reusch said.

“When I’m looking at the patient in the room and thinking about what a drug can do for them, I want to respect the fact that, while blood pressure lowering and cholesterol lowering in a majority of patients can be quite straightforward, glucose lowering is not always so, because it requires so much behavioral change on the part of the patient,” Reusch said.

“The number 1 fact that we all have to contend with when we’re thinking about cardiovascular disease and diabetes is shortened life expectancy,” Reusch said. “When you place this in the context of coexistent cardiovascular disease and diabetes, this is really a big deal. But it’s a made a bigger deal by the fact that the age of onset for the development of diabetes is now younger and younger, most likely related to our obesity epidemic.”

Patient-centered guidelines

In people with type 2 diabetes and preexisting CVD, how aggressive a provider may want to be with therapies should depend on the patient’s life expectancy, Reusch said.

“We [at ADA] have the bias — which is not shared by all guidelines — that if a patient has a shortened life expectancy, then I am going to be a little less aggressive,” Reusch said. “If I have a patient with a long-life expectancy, like diagnosis at age 30 [years], then I’m going to be very aggressive. But I’m going to have to place things into context, and I have to place them into context with the patient.”

The lengthy ADA Standards of Care, with 15 separate position statements, can come off as big and complicated, Reusch said, but one important takeaway is that each aspect of the recommendations includes lifestyle management as a component of therapy. More investment must be made in strategies to improve team-based treatment for people with diabetes, enabling them to make meaningful and sustainable behavioral changes, she said.

“My own personal perspective is that while all the cardiovascular outcomes studies have looked at people with established cardiovascular disease, it behooves us not to forget that part of the modifiable cause for diabetes is poor lifestyle choice,” Reusch said. “So, medical nutrition therapy and physical activity have to be kept front and center in all of our guidelines.”

Recommended next steps

According to the 2018 Standards of Care, adults diagnosed with type 2 diabetes should be prescribed lifestyle management, set an HbA1c target with their provider, and initiate therapy based on their HbA1c, typically starting with metformin as a first-line agent unless there are contraindications.

If the patient does not achieve their HbA1c target approximately 3 months and the patient does not have atherosclerotic cardiovascular disease, providers should consider a combination of metformin and any one of the preferred six treatment options: sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT2 inhibitor, GLP-1 receptor agonist or basal insulin, according to the recommendations.

For patients with atherosclerotic cardiovascular disease, Reusch said, add a second agent with evidence of CV risk reduction after consideration of drug-specific and patient factors, such as a GLP-1 receptor agonist or an SGLT2 inhibitor.

“I really want to take time to think about this — finally, the ADA has gotten to the party,” Reusch said, referring to the recommendations for SGLT2 inhibitors and GLP-1 receptor agonists. “We are finally endorsing these therapies. We waited for the FDA and for the evidence to do this, and now I feel confident and comfortable that now, we are in a sea change. Not only did we endorse that guideline, but now we’re working in a collaborative with [the American College of Cardiology] and [the American Heart Association] and, hopefully, a collaborative with this group and [the European Association for the Study of Diabetes], to really get this job done. This is the statin sea change of diabetes management. We really need to change how we’re thinking.”

Still, Reusch said, traditional risk factor modification still maintains the top priority across guidelines.

“The primary goal of antihyperglycemic therapy is to lower glucose, and combination therapy is very often needed,” Reusch said. “Polypharmacy, cost [of medication], durability must be considered, and the studies currently demonstrating dual efficacy of antihyperglycemic agents are only in people with high risk and established cardiovascular disease. And, we have no data at the moment for type 2 diabetes and metformin.”

Gaps in understanding

Several gaps in understanding remain regarding the underlying biology of type 2 diabetes therapies and health care delivery strategies, Reusch said. The mechanisms for the interaction between GLP-1 receptor agonists and SGLT2 inhibitors and decreased CVD and congestive heart failure, for example, need clarification, Reusch said, and the timing and physiologic context in which these drugs are administered needs to be tested. Additionally, there is no data demonstrating a role for these agents in primary prevention, despite theoretical benefit, Reusch said.

On the health care delivery side, glucose management remains challenging during brief patient visits, primary care providers and people with diabetes need support when initiating new medications, and diabetes remains a chronic disease with social stigma, she said.

“Where is the benefit? It’s going to be in consensus and harmonization and us building guidelines that make sense to everyone,” Reusch said. – by Regina Schaffer

Reference:

Reusch JEB. ADA recommendations for pharmacological management of DM & CVD. Presented at: Heart in Diabetes Clinical Education Conference; July 13-15, 2018; Philadelphia.

ADA. Standards of Medical Care in Diabetes – 2018. Available at: care.dinewabetesjournals.org/content/41/Supplement_1.

Disclosure: Reusch is president of medicine and science for the ADA.