Carefully Consider Cardiovascular Effects of Diabetes Drugs

Some therapies harbor cardiovascular benefits while others may pose significant risks.

NEW ORLEANS — As new agents continue to revolutionize the treatment of diabetes, endocrinologists must weigh treatment options more carefully when treating patients with diabetes and comorbid cardiovascular disease (CVD).

At AADE 2015, the annual meeting of the American Association of Diabetes Educators, Emily Weidman-Evans, PharmD, BC-ADM, CPE, clinical associate professor at Louisiana State University Health Sciences Center (LSU Health) in Shreveport, discussed the complexities of treating this patient.

During her presentation, Weidman-Evans explained that various diabetes therapies may affect cardiovascular (CV) health in different ways.

“The data show that some of the drug classes we use to treat type 2 diabetes may also improve cardiovascular outcomes. Interestingly, some are old and expected and some possibly not. Clinicians should consider these data when treating patients at high risk for cardiovascular disease as opposed to just looking at blood glucose-lowering ability,” Weidman-Evans said.

In 2007, a very large meta-analysis linked the thiazolidinedione rosiglitazone (Avandia) with an increased risk for myocardial infarction (MI). As a result, the drug was placed under a restricted access prescribing program.

“It was in response to this that the FDA mandated that all new diabetes mellitus drugs provide data showing cardiovascular safety, although the manufacturers did not have to provide any proof of cardiovascular benefit. Rosiglitazone is now fully back on the market with no restrictions,” Weidman-Evans said.

She noted that if a patient with diabetes has a high risk for CVD, they need to have individualized tailored therapy. For instance, Weidman-Evans suggests that clinicians consider a higher HbA1c goal of 7.5% to 8%, which correlates to an average glucose of 170 mg/dL, in some patients with heart failure. Clinicians should also stick with metformin as first-line therapy and avoid older sulfonylureas and rosiglitazone, she added.

Besides dosing insulin in a manner to avoid hypoglycemia, clinicians may want to consider pioglitazone as well as an alpha-glucosidase inhibitor as earlier treatment options. Another option to consider based upon CV outcomes is glucagon-like peptide-1 (GLP-1) agonists, according to Weidman-Evans.

“We need to look at surrogate markers and outcomes beyond blood glucose control, since the link between that measurement and macrovascular complications is still unknown. While it is well accepted that metformin improves cardiovascular risk, many clinicians will not know that the data support the use of alpha-glucosidase inhibitors or possibly the new GLP-1 agonists to lessen macrovascular risk,” Weidman-Evans told Endocrinology Advisor.

“We need to consider their clinical priorities when selecting drug therapy, especially in those at high risk for cardiovascular disease.”

Age matters as well, according to Weidman-Evans, as it is the biggest risk factor for CVD when looking at the American College of Cardiology (ACC)/American Heart Association (AHA) risk calculator. In addition to having diabetes, older patients are already at a higher risk, and that must be addressed, which can make treatment even more complicated.

“Older patients also have other factors that must play into drug selection, such as changes in renal function, gastrointestinal issues and often multiple other drugs that potentially interact with one another. It just highlights the need even more for looking at the whole patient and not just the glucose numbers,” said Weidman-Evans.

Metformin is still, in nearly every case, going to be tried as first-line pharmacologic therapy because of its established benefits beyond lowering glucose, she noted. However, some of the newer classes of drugs, most notably the incretins, are good options for those patients who cannot tolerate metformin.

Although there are now 12 classes of diabetes medications, some agents may help lower blood glucose but may or may not impact CVD. As CVD is the No. 1 cause of death in people with diabetes, clinicians should take this into consideration, Weidman-Evans said.


  1. Weidman-Evans E. F05 – How Sweet is Your Heart? Cardiovascular Effects of Diabetes Drugs. Presented at: AADE 2015; Aug. 5-8, 2015; New Orleans.