Empagliflozin Has Similar Efficacy Across Subgroups, More Data Needed in CKD: Dr Jennifer Green

Data on empagliflozin in chronic kidney disease (CKD) showed the drug had similar efficacy across subgroups, but more data is needed to really understand the benefit of the drug in CKD, saidJennifer Green, MD, professor of medicine at Duke University School of Medicine, member of Duke Clinical Research Institute, and EMPA-KIDNEY collaborator.

What impact did race and other demographic factors have regarding efficacy of empagliflozin in CKD?

There are very detailed data regarding the effects of empagliflozin compared to placebo, across a very wide number of subgroups of potential interest. We saw no differences in the effect of empagliflozin, or the benefit of empagliflozin, in women compared to men, or in people who were in different locations around the world. The effect appears to be very, very consistent. I'm happy to say, that in the United States, we successfully enrolled a very, very diverse patient population—really representative of people with kidney disease in this country.

Can you review the mechanism of action for empagliflozin and discuss why this class of drugs appears to affect not only diabetes, but also kidney disease?

Everyone wants to know why the SGLT2 [sodium-glucose cotransporter 2] inhibitors provide the clear cardiovascular and kidney benefits that have been clearly proven in EMPA-KIDNEY. These drugs were first created because we know that they reduce glucose reabsorption in the kidney. With people with type 2 diabetes, blood glucose levels will be lowered because there's more glucose put out into the urine.

Now, that does not explain the vast array of organ benefits that we see with use of empagliflozin under a variety of theoretical physiologic effects that might be of benefit, such as positive changes in blood pressure, hematocrit levels, and probably favorable hemodynamic changes in the kidney. We don't know those exact reasons with certainty at this time. However, I would encourage people to continue to investigate that, but not wait for that information to be available before implementing these effective medications in clinical practice.

The rates of hospitalization for heart failure deaths from cardiovascular causes, as well as death from any cause, was improved, but remain nonsignificant for those given empagliflozin vs placebo. What takeaways should clinicians understand about these findings, and what additional research is warranted here?

There were numerically fewer of those events in the patients who received empagliflozin compared to those who received placebo, but the reduction was not statistically significant. Remember that the trial was powered specifically to answer the question related to the primary outcome, and there were not very many of the kinds of events that you mentioned that had time to occur during the trial. Thus, the trial probably was not powered and did not go on long enough for us to accumulate enough of those events to really determine the effect of the medication with confidence.

However, what we did see, with respect to the results, are very similar to findings in other trials, which studied SGLT2 inhibitors in similar patient populations. Remember that the trial was halted early due to significant efficacy in reaching or reducing the primary outcome. In fact, the median duration of follow up in EMPA-KIDNEY at 2 years was shorter than that in the other 2 CKD trials in the class.

Speaking generally, what sorts of insurance barriers, if any, have you had trying to prescribe “flozins” for patients?

I prescribe SGLT2 inhibitors very often for diabetes, kidney disease, and cardiovascular disease, and sometimes for all of those things in the same patient. We don't have enough time to review the different strategies and opportunities that seem to work best depending on an individual's particular insurance coverage or lack thereof. However, it's very clear that the clinics that have been very successful in doing this usually have 1 or even 2 people who are really dedicated to understanding what each person's individual insurance coverage will allow them to obtain, and really help to navigate that system.