Anti-Diabetes Medications and CVD Prevention

Robert A. Gabbay, MD, PhD: Glucose control is certainly an important part of the management of diabetes. We know that, and we’ve known that for a long time. It can prevent, certainly, microvascular complications—kidney, nerve, eye damage. But when it comes to preventing cardiovascular disease, it probably only has a small role in comparison to the role of blood pressure and cholesterol control. That’s been sort of the state of knowledge for a while. Then, in the last year-and-a-half to 2 years, there’s been a real explosion of knowledge that really relates to diabetes drugs that are used to control blood glucose. It turns out they have an added benefit to reduce cardiovascular disease.

We only had 1 drug, for many years, that fell into that category. In other words, it was a drug used to treat diabetes that lowered cardiovascular mortality—that was metformin. In the last year-and-a-half to 2 years, we now have 2 more classes of drugs. One is the GLP-1 (glucagon-like peptide-1) agonist that was shown in the LEADER Trial to decrease cardiovascular mortality. That was a big discovery. And then, the SGLT2 (sodium-glucose co-transporter-2) inhibitors, similarly, have shown to decrease cardiovascular mortality as well. Both of those drugs, in the studies, demonstrated their reduction of cardiovascular mortality in people with significant risk for cardiovascular disease. So, we know that those drugs lower cardiovascular risk in those that are at very high risk.

What we don’t know, yet, is whether those drugs could also be beneficial in terms of cardiovascular risk in people with even lower risks at baseline of cardiovascular disease. That’s going to be the next step in the research progression. But overall, we’ve made a lot of progress here and we have, now, some new tools that treat not only blood glucose but also lower cardiovascular mortality.

Scott Solomon, MD: As a cardiologist, I don’t primarily treat patients with antidiabetic medications. But many of my patients are on antidiabetic medications. We know that the more of these medications they’re on, the worse their metabolic risk, and the worse their diabetes. I’d like to have them on fewer medications if I can. Certainly, those patients who are on insulin are at increased risk as well. We know that patients with lower blood sugars will have a lower risk, overall. What we don’t know is, if we lower those blood sugars, can we reduce their cardiovascular risk? There’s a hint in that with metformin. There’s also a hint in that with GLP-1 agonists. We think we can probably reduce cardiovascular risk with an SGLT2 inhibitor. The SGLT2 inhibitors are actually quite interesting, because these are drugs that essentially cause us to urinate out glucose. So, it lowers the threshold at which glucose is excreted by the kidneys. It lowers hemoglobin A1c, and lowers glucose in the blood.

But the benefit that was seen in the EMPA-REG trial may not be due to that effect. It may be due to the effect that you’re actually getting rid of both glucose and sodium. To some extent, they may be functioning as diuretics. But one of the most important findings in the EMPA-REG trial, which was a study of empagliflozin in patients with diabetes, was a reduction in heart failure. It suggests that these drugs may actually have a benefit beyond glucose lowering.

Transcript edited for clarity.