ADA recommends cardioprotective antihyperglycemic drugs for patients

Recent studies that confirm the cardiovascular benefit of some antihyperglycemic agents are shaping the newest therapeutic recommendations for patients with type 2 diabetes and co-morbid atherosclerotic cardiovascular disease.

Treatment for these patients – as all with diabetes – should start with lifestyle modifications and metoformin. But in its new position movement, the American Diabetes Association now recommends that clinicians consider adding agents proved to reduce major cardiovascular events and cardiovascular death – such as the sodium glucose cotransporter-2 (SGLT2) inhibitor empagliflozin or the glucagon-like peptide 1 (GLP-1) agonist liraglutide – to the regimens of patients with diabetes and ASCVD.

The medications are indicated if, after being treated with lifestyle and metformin therapy, the patient isn’t meeting hemoglobin A goals. But clinicians may also consider adding these agents for cardiovascular benefit alone, even when glucose control is adequate on a regimen of lifestyle modification and metformin, with dose adjustments as appropriate, she said in an interview.

The recommendation to incorporate agents with cardiovascular benefit is related directly to data from two trials, LEADER and EMPRA-REG, which support this recommendation. All of these cardiovascular outcome trials included a majority of patients who were already on metformin. “We developed these evidence-based recommendations based on these trials and to appropriately reflect the populations studied.”

The ADA’s “Standards of Medical Care in Diabetes 2018” is the first position statement from any professional society to provide specific recommendations for the incorporation of these newer antihyperglycemic agents for their cardioprotective benefit in the treatment of algorithm for type 2 diabetes. But the document provides much more than an algorithm for treating patients with concomitant ASCVD. It is a comprehensive clinical guide covering recommendations for diagnosis, medical evaluation, comorbidities, lifestyle change, cardiovascular risk management, and treating diabetes in children and teens, pregnant women, and patients with hypertension.

The 2018 update contains a number of new recommendations; more will be added as new data emerge, since the ADA intends it to be a continuously refreshed “living document.” This  makes it especially clinically useful. A member of the writing committee of the American Association of Clinical Endocrinologist’s diabetes management guidelines feels ADA’s previous versions have not been as targeted as this new one and, hopes, its subsequent iterations.

“This is a nice enhancement of previously published guidelines for diabetes therapy.” “For the first time, ADA is providing some guidelines in terms of which agents to use. It’s definitely more prescriptive that it was in the past, when, unlike the AACE Diabetes Guidelines, it was a palette of choice for clinicians, but with very little guidelines about which agent to pick. The guideline for patients with cardiovascular disease in particular is big news because these antihyperglycemic agents showed such a significant cardiovascular benefit in the trials.”

While the document gives a detailed algorithm of advancing therapy in patients with ASCVD, it doesn’t specify drug class after metformin therapy in patient without ASCVD. Instead, it provides a detailed listing the drug-specific effects and patient factors to consider when selecting from different classes of antihyperglycemic agents (SGLT2 inhinbitors, GLP-1 agonists, DPP-4 inhibitors, thiazolidinones,sulfonylureas, and insulins). The table notes the drugs’ general efficacy  in diabetes, and their impact on hypoglycemia, weight and gain, and cardiovascular and renal health. The table also includes the Food and Drug Administration black box warnings that are on some of these medications.

Another helpful feature is a cost comparison of antidiabetic agents. Last year we added comprehensive cost tables for all the different insulins and noninsulins, and this year we added a second data set of cost information, to assist the provider when prescribing these agents.”

“In this document, ADA is urging providers of care to ask about whether the cost of their diabetes care is more than patients can deal with. They present tables which compare the costs of the current blood glucose – lowering agents used in the US, and it is plain to see that many patients, without insurance coverage, will find some of the medications unaffordable. They also provide data that show half of all patients with diabetes have financial problems,” and he suspects that medication costs are an important component of their financial insecurity.

The document also notes data from the 2017 National Health and Nutrition Examination Survey, which found 10% of people with diabetes have severe food insecurity and 20% have mild food insecurity.

“Another thing that document points out is that two-thirds of the patients who don’t take all their medications due to cost don’t tell their doctor. The ADA is making the point that providers have a responsibility to ask if a patient is not taking certain medications because of the cost. ”

While the treatment algorithm for patients with ASCVD will likely be embraced, another new recommendations may stir the pot a bit. The section on cardiovascular disease and risk management sticks to a definition of hypertension as 140/90 mm Hg or higher – a striking diversion from the new 130/80 mm Hg limit set this fall by both the American College of Cardiology.

Again, this recommendation is grounded in clinical trials, which suggest that people with diabetes don’t benefit from overly strict blood pressure control. The new AHA/ACC recommendations largely drew on data from SPRINT, which was conducted in an entirely nondiabetic population. “These gave a clear signal that a lower BP target is beneficial to that group.”

“This recommendation is based on current evidence for people with diabetes.” “We maintain our definition of hypertension as 140/90 mm HG or higher based on the result of large clinical trials specifically in people with diabetes but emphasize that intensification  of antihypertensive therapy to target lower blood pressures (less than 130/80 mm HG) may be beneficial for high-risk patients with diabetes such as those with cardiovascular disease. We are constantly assessing the evidence and will continue to review the results of studies for potential incorporation into recommendations in the future.