Impact of EMPA-REG OUTCOME

John B. Buse, MD, PhD: The EMPA-REG trial was a trial of empagliflozin versus placebo. It studied 2 different doses of empagliflozin, 10 mg and 25 mg once a day, versus matched placebo, and went on for approximately 3 years. In the trial, the primary endpoint was the first occurrence of a heart attack, a stroke, or cardiovascular death. And very importantly, those outcomes were blindly adjudicated, so the people who were deciding whether the event actually happened or not weren’t aware of what drug or dose they were assigned to.

In the EMPA-REG trial, there was a 14% reduction in the primary endpoint, the first occurrence of heart attack, stroke, or cardiovascular death; a 38% reduction in cardiovascular death; a 35% reduction in heart failure or hospitalization; and a meaningful reduction in either the advancement or progression of a chronic kidney disease. So, it was pretty much a slam-dunk win for empagliflozin in that trial.

And to me, one of the most impressive things about the results is that the benefits were pretty similar between the 2 doses: 10 mg and 25 mg. So, it’s almost as if there were 2 trials done because we had benefits at both doses for most of those endpoints. From a safety perspective, their performance was pretty stellar as well. We know that these drugs are associated with an increased risk of vaginal yeast infections in women, and balanitis, or basically yeast infection of the foreskin, in men. But otherwise, there was very little evidence of any adverse events with the drug, specifically minimal imbalances in urinary tract infections, bone fractures, and other outcomes that are mentioned in the package insert of the drug.