Lucia Novak discusses the importance of testing for cardiovascular outcomes of diabetes treatments and compares the cardiovascular effects of several diabetes drugs.
Patients with type 2 diabetes are at greater risk of cardiovascular disease—they’re 2-3 times more likely to die of heart disease or to have a stroke, according to the US Centers for Disease Control and Prevention. Given the stakes, clinicians caring for patients with type 2 diabetes should be aware of how diabetes medications are tested for cardiovascular outcomes and what the cardiovascular implications of various diabetes medications are.
Lucia Novak, an adult nurse practitioner who specializes in diabetes management, spoke with MD Magazine® about the links between type 2 diabetes and cardiovascular disease, as well as the cardiovascular outcomes trials required of all new diabetes medications.
Novak also discussed the cardiovascular effects of currently available diabetes medications, including the 3 that actually provide cardiovascular benefits to patients: liraglutide, a GLP-1 receptor agonist, and empagliflozin and canagliflozin, both SGLT-2 inhibitors.
“I tell my patients ‘it’s not just about your sugar, sugar,’” says Novak. “Diabetes to me is heart disease, and so when I’m looking at treating the diabetes I have to take into consideration this underlying heart disease that they likely have.”
Watch the first part of Lucia Novak’s diabetes discussion, where she covers some of the gaps that remain in diabetes care and what providers can do to bridge those.
Why are drugs for type 2 diabetes tested for cardiovascular effects?
What has happened more recently, and that is since 2008, when one of our thiazolidinedione medications—which was rosiglitazone or Avandia—was believed to actually increase the risk of heart attack in patients with diabetes. And again, patients with diabetes already have a tremendous increased risk of having a heart event over the general population—we’re looking at 4- to 6-fold over the general population. So, having a diabetes medication that could actually increase that risk is definitely a no-go. The FDA mandated at that point, 2008, that every drug that comes to market for the indication of treating diabetes for type 2 patients, has to show cardiovascular safety.
How are these cardiovascular outcomes trials conducted?
These studies are done on top of standard of care. What that means is that when these patients are enrolled in these cardiovascular outcomes trials, their blood pressure and their cholesterol as well as their glycemic control are being adjusted simultaneously to meet whatever targets have been determined during the time that the study was taking place.
So, it’s not just that they’re put on these drugs and let’s see what happens. They’re put on these drugs in addition to their blood pressure, statin medication, aspirin, beta blocker if they had an MI [myocardial infarction]. All of those things are already in place. So, on top of that is really what we’re looking for.
What do guidelines recommend for providers treating patients with T2D?
So, in 2018 the ADA [American Diabetes Association] came out specifically in their guideline stating that once you have a patient that’s on monotherapy, which is typically after or in addition to therapeutic lifestyle, we start with metformin. [It’s] weight-neutral, doesn’t cause hypoglycemia, has been around for a really long time, and has shown some cardiac benefit with the UKPDS (United Kingdom Prospective Diabetes Study) follow-up data.
What do we do after metformin? And as I told you we have 11 classes of drugs to choose from. How do you know what to go to? And so, the question that needs to be asked is: does your patient with type 2 diabetes have underlying cardiovascular disease? And if they have underlying cardiovascular disease, that is where we then turn our attention to these cardiovascular outcomes trials.
How do current diabetes drugs compare on cardiovascular outcomes?
So, we have many drugs that have shown that they’re at least safe for use in our patients with diabetes. But we also have shown some agents—not necessarily complete classes, but some agents within class—that have also demonstrated not just safety, but actual benefit to patients with underlying cardiovascular disease.
For instance, in the GLP-1 receptor agonist class, we have 1 drug, liraglutide, that has actually shown a reduction in that MACE [major adverse cardiovascular event] outcome compared to standard of care. We also have in the SGLT-2 inhibitor class, 2 drugs that have shown reduction of MACE outcomes. That would be your empagliflozin or your canagliflozin medications. So, we have 3 drugs right now—1 in the GLP-1 receptor agonist class and 2 in the SGLT-2 inhibitor class—that have shown cardiovascular disease protection in patients with established cardiovascular disease. So that is now where we as clinicians need to start deciding—when we’re choosing medications and intensifying treatment—what is going to benefit our patient.
I tell my patients “it’s not just about your sugar, sugar.” Diabetes to me is heart disease, and so when I’m looking at treating the diabetes I have to take into consideration this underlying heart disease that they likely have.