NCHR Testimony on Empagliflozin to Improve Glycemic Control

Nina Zeldes, National Center for Health Research, November 13, 2019

Thank you for the opportunity to speak here today. My name is Nina Zeldes and I am a Senior Fellow at the National Center for Health Research. Our research center analyzes scientific and medical data to provide objective health information to patients, health professionals and policy makers. We do not accept funding from drug and medical device companies, so I have no conflicts of interest.

Drugs that help patients manage their Type 1 Diabetes and improve their quality of life would greatly benefit patients. However, it’s not clear that this drug fulfills those goals.

The data for the 2.5 mg dose rests on a single phase 3 trial. As we all know, replication is the key to scientific evidence. Independent clinical trials could have a smaller or larger effect due to differences in the demographics or comorbidities of patients and other factors.

This is of particular importance here, as there was a lack of diversity in this study. For example, 97% of the 241 patients in the treatment arm were white. Although a subgroup analysis was performed on nonwhites, there were obviously too few – 7 in the treatment arm – to provide meaningful data about safety or efficacy. Additionally, only about 30% of patients were enrolled in North America, and no numbers were provided regarding the number of patients in the United States.

There are vast differences in obesity, eating and drinking habits, and other health habits such as smoking and exercise, as well as access to healthcare.  Many of these variables could affect the risks and benefits of this drug for U.S. patients. It is therefore not clear how applicable the data are for the US population that the sponsor seeks approval for.

The trial was also of a very short duration, considering this is a drug that is expected to be taken for many years by patients. The long-term risks and benefits were not studied, so we don’t know whether the benefits are likely to outweigh the risks long-term. And while a reduction of HbA1c is an accepted surrogate endpoint for these products, it is not clear if the small improvement seen in the clinical trial is clinically meaningful for patients.

It is also important to point out that the patients in this one trial were much more carefully selected and monitored than they will be in the real world of medical practice.

There is no urgency to approve this drug, given that there are so many unknowns.  The mission of the FDA is to provide patients with real, clinically meaningful benefits.  As advisers to the FDA, it is essential that you speak on behalf of patient safety as you carefully consider and weigh how this drug could help or harm patients.