Diabetes Therapy and Cardiovascular Outcomes: An Update - Episode 15
John Anderson, MD: The EMPA-REG trial and results from the EMPA-REG trial that were released in Stockholm in September of 2015 were absolutely groundbreaking in terms of now, for the very first time, having a diabetes drug that showed significant cardiovascular risk reduction. I was fortunate enough to be there in Stockholm. It was like going to a rock concert. People were running in trying to find chairs and tables, because they knew that there was a positive outcome. No one knew exactly how profound the outcome was. We found out that it met its primary MACE endpoint, MACE being major adverse cardiovascular events—that’s nonfatal MI, nonfatal stroke, and cardiovascular death—and that was a 13% risk reduction, and there was a nice, polite applause. But when they showed that there was a 38% reduction in cardiovascular death, people were blown away. There was cheering and standing ovations.
You now have a diabetes drug, and the curves separated very early on. So, the benefit occurred within the first 3 or 4 months of treatment. The biggest concern people have now is, what in the world is the reason for this, and what are the possible mechanisms? But it is really important to note that despite hemoglobin A1C, this cardiovascular risk reduction occurred. Now, these were all patients who had cardiovascular disease. This is what we would call a secondary prevention. But this empagliflozin molecule now has an FDA indication for reduction of cardiovascular risk with no mention of hemoglobin A1C. It’s the first drug to actually have 2 indications from the FDA. Remember that, in the background of this, all of these other cardiovascular trials with ORIGIN, insulin, and all of the DPP-4 inhibitors have all been safe but neutral. So, this was the very first one that showed not only a positive result but a dramatic positive result.
The EMPA-REG trial now focuses everybody on—the treatment of type 2 diabetes is not only about glycemic control, it’s also about reduction of macular vascular risk. So, you have patients with cardiovascular disease, and you’re talking about a 38% reduction in cardiovascular death. The number needed to treat is somewhere around 1 out of the 44 patients you treat over a 3-year period of time, which is about the duration of the trial. You saved 1 life.
Now, that’s pretty important stuff. If you have type 2 diabetes and you have cardiovascular disease, and I put myself in that position, don’t I want to be on a medication like that? And so, now we’re starting to look at our patients differently. Do they have cardiovascular disease? Do they not? If they do, right now empagliflozin is the only FDA-recommended treatment for risk reduction in a diabetes drug.
What’s interesting about that is, guess who’s getting in on the game? The cardiologists. So, the cardiologists have taken up the mantle of this and said, “We need to be doing a good job with this as well.” And I didn’t mention that in the EMPA-REG trial, there was a 35% reduction in admissions for heart failure. So, not only was there the primary MACE, cardiovascular death, and reductions in admissions for heart failure, but also some really interesting renal data and a possible renal-protected mechanism for empagliflozin. It’s a whole new day when we’re talking about diabetes drugs now.