This decision was expected, as the FDA advisory committee voted 14-2 against recommending approval empagliflozin 2.5 mg for type 1 diabetes in November. The reason the advisory committee voted the way it did was because of the adjudication of diabetic ketoacidosis (DKA) and the lack of a demonstrated benefit/efficacy with this dose. The between-group HbA1c difference of –0.26% was attributable to a 0.2% HbA1c increase in the placebo group and a –0.05% decrease in the empagliflozin 2.5 mg group. If the lower dose provides so little benefit, then why bother? Why introduce possible adverse effects?
There were also issues with study design, which did not reflect the diversity of the overall U.S. population.
I do hope this is not the end of the road. Many of us are eager to continue to explore noninsulin therapies for type 1 diabetes, but there is a “pause” preventing any excitement in this area, for the reason that the FDA wants some sort of assurance that these people with type 1 diabetes are not going to die from DKA.
What I think may come out of this are new methods to noninvasively measure ketones. There are companies exploring this very idea and, in early studies, looking into continuous measurement of ketones that is similar to continuous glucose monitors. Of course, for ketones, frequency does not have to be every 5 minutes like with a CGM; this could be done once every 20 or 30 minutes. If this happens, and someone conducts a small study demonstrating you can mitigate the risk for DKA, the FDA may look at these drugs differently. For now — at least for the next year or two — I would not expect to see other noninsulin therapies for type 1 diabetes go before the FDA. Instead, SGLT2 inhibitors will continue to be used off-label in select patients with type 1 diabetes, who we ask to regularly monitor ketones.
Satish K. Garg, MD
Professor of Medicine and Pediatrics
Barbara Davis Center for Diabetes
University of Colorado Denver
Disclosures: Garg reports he has served on advisory boards for Dexcom, Eli Lilly, Lexicon, Mannkind, Medtronic, Merck, Roche and Sanofi, and received research grants through his institution from Animas, Dario, Dexcom, Eli Lilly, JDRF, Lexicon, Medtronic, Merck, NIDDK, Novo Nordisk, Sanofi and T1D Exchange.