Recent research continues to show that glucose-lowering agents such as GLP-1 liraglutide receptor agonists and semaglutide and SGLT-2 inhibitors empagliflozin and canagliflozin reduce the risk of major cardiovascular events. This is a major advance but also opens the door for further research and education.
In this video, James Januzzi, MD, Roman W. DeSanctis Endowed Bachelor of Clinical Distinguished in Medicine and director Dennis and Marilyn Barry Fellowship in Cardiology Research at the Massachusetts General Hospital in Boston, discuss the latest studies and explain how the American College of Cardiology and the American Diabetes Association work together to provide practical guidance for cardiologists.
The following is a transcript of his statement:
I am here at the American Heart Association in Chicago where we hear new data about the importance of interactions between the endocrine system and the cardiovascular system. Especially patients with diabetes have a very high risk for cardiovascular disease and when patients with diabetes get cardiovascular disease, they have a much worse prognosis. And this is not only talking about macrovascular complications such as coronary disease, but also heart failure, which seems to be a very complicated problem for diabetic patients.
Why is this topic even the point of discussion? Well, it turns out that thanks to the Food and Drug Administration Guide in 2008 about new diabetes drugs that need to show cardiovascular safety, we later found out that some new classes of diabetes drugs have benefits, not only for safety, but are actually beneficial in reducing cardiovascular events.
To frame the situation, traditionally, we have seen diabetes medicine as a therapy to reduce glucose – called the glucocentric view – which we use it, they reduce glucose and they reduce microvascular complications such as kidney dysfunction, neuropathy and retinopathy. But generally, studies looking at diabetes drugs have not shown benefits in large-scale complications such as coronary disease or heart failure. In this space there are two new classes of drugs, peptide receptor agonists such as glucagon, GLP-1 receptor agonists, and sodium-glucose inhibiting drugs cotransporter-2 or SGLT2.
So these two classes of drugs lower glucose simply, but they are good drugs for diabetes. And they use the effect in different ways. Regardless of their working mechanism, these drugs in testing cardiovascular results examined their safety, we actually found that each independently reduced cardiovascular risk.
So let's start first with the GLP-1 receptor agonist. This is an injection drug class that lowers blood glucose through a number of mechanisms – one of which is that they reduce gastric emptying, they reduce glucagon secretion. So as a result, they reduce blood glucose as a downstream effect. They cause weight loss, partly because they reduce appetite. And interestingly in trials of cardiovascular outcomes, these drugs appear to reduce, especially atherothrombotic complications, myocardial infarction, stroke, and cardiovascular death. So that's kind of interesting.
And one drug, liraglutide, has cardiovascular indications to reduce risk. The sodium-glucose drug cotransporter-2, the SGLT2 drug, is oral – they are pills, they lower blood glucose by inducing glycosurisia, they make you release glucose. They are also simple effective for lowering blood glucose. But quite remarkable, in some clinical trials we now see a large reduction in cardiovascular risk in patients with diabetes who are treated with these drugs. Empagliflozin and the results of the EMPA-REG study reduce cardiovascular deaths and the incidence of new onset heart failure.
In CANVAS research, canagliflozin reduces cardiovascular death and heart failure. And here at the American Heart Association meeting, the DECLARE TIMI-58 trial showed that dapagliflozin reduces the risk for, in particular, the incidence of heart failure. There is some heterogeneity in results for SGLT2 inhibitors, whereas empagliflozin appears to reduce cardiovascular death and heart failure, somewhat similar to canagliflozin.
In the DECLARE study, dapagliflozin reduced heart failure, but did not seem to scratch the surface of cardiovascular death.
Regardless, the bottom line of all these studies, whether with GLP-1 receptor agonists or SGLT2 inhibitors, really shows that we now as cardiologists must think about our patients with diabetes, not only regarding their risk for microvascular complications, which is true really owned by diabetics and primary care doctors honestly, but now as cardiologists, we have to think about their macrovascular risk in terms of coronary disease and heart failure.
So far, the American College of Cardiology and American Diabetes Association have now collaborated in a relationship to prepare education guides for cardiologists in connection with this topic. ACC has an upcoming document of expert consensus decision lines that focus precisely on when, how, and why to start new cardiovascular risk reduction drugs for patients with diabetes.
We will provide knowledge about when cardiologists should think about using SGLT2 inhibitors or GLP-1 receptor agonists – emphasizing again and again that this is not about lowering blood glucose. We move away from the glucocentric view and really try to focus more on reducing cardiovascular risk. It's amazing that even thinking about using drugs that have never been considered cardiovascular drugs in this way, but the fact is that these patients have a huge risk. It is very important that cardiologists enter the battlefield here and really try to better manage these patients.