Advances in the Management of Cardiometabolic Syndrome - Episode 4
Robert A. Gabbay, MD, PhD: SGLT2 (sodium-glucose co-transporter-2) inhibitors are an exciting new class of drugs. There have been 2 findings that have really been, I think, an important aspect to changing the way we think about caring for people with diabetes. First was the EMPA-REG study, which was a cardiovascular safety study with empagliflozin. They were only looking to see if the drug was safe. It turned out, not only, that it was safe, but it actually lowered cardiovascular risk, significantly.
That then brought up the question, was this specific to that 1 analog, or could it be part of a class effect of the SGLT2 inhibitors? The study that helped to look at that was a retrospective study that was presented at the 2017 American College of Cardiology Meeting—CVD-REAL. They looked at a large data set and identified that those patients that were on SGLT2 inhibitors had a significantly lower risk of hospitalizations for congestive heart failure.
Now you have a drug for diabetes that not only improves blood glucose control and decreases cardiovascular mortality, but also decreases hospitalizations for congestive heart failure (a very high cost event in managing patients). Understanding the other added benefits of this class of drugs really makes us think of it much earlier in the armamentarium for the management of diabetes.
Scott Solomon, MD: One of the most exciting things to come out of the 2017 American College of Cardiology Meeting, that we held about a week ago, was the FOURIER trial, that used a new drug, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, which is a novel way to lower low-density lipoprotein (LDL) cholesterol. It’s much more effective than the statins and the standard ways we lower LDL cholesterol. This was a study that was done on top of statin use. These patients had a 15% reduction in the primary outcome of the trial, which was a composite primary outcome—what we would call “MACE-plus.” And it’s very exciting because it suggests that if we can lower LDL further, we can lower risk in these patients even further. Unfortunately, these drugs are also expensive and they are not going to be used first-line in patients with coronary artery disease or those at-risk. They’re going to be, I think, niche drugs for a while.
Sacubitril/valsartan is an angiotensin receptor-neprilysin inhibitor that, in the PARADIGM-HF trial, was shown to significantly reduce cardiovascular death, heart failure hospitalization, and all-cause mortality. We recently did a post hoc analysis from the PARADIGM-HF trial looking at the effect of sacubitril/valsartan on glycemic control—specifically hemoglobin A1c. And we found, somewhat unexpectedly, that there was a highly significant reduction in hemoglobin A1c in the patients who received sacubitril/valsartan compared to those who received enalapril.
It wasn’t an extremely large effect in magnitude, but it was highly significant. It was about .2 overall points of hemoglobin A1C. But what was actually even more important was that there was a 30% reduction in the percentage of patients who got started on insulin who were diabetic in the trial. That’s important if you think about treating patients with diabetes and heart failure. We want to make sure that what we’re doing for their heart failure isn’t going to make their diabetes worse. And what we think with sacubitril/valsartan is that, if anything, we are improving glycemic control and we are reducing the likelihood that they would need a new antidiabetic medication like insulin.
Transcript edited for clarity.