New Debate About Flozins for Diabetes

Whenever possible, I like to link my article thematically. Back on July 19 of this year, I published a Talking Therapeutics article discussing dapagliflozin vs empagliflozin in patients with heart failure. As you regular readers may recall, that nonrandomized study found a signal for superiority with empagliflozin.

SGLT2 inhibitors are now indicated for so many diseases that it’s easy to forget that they were originally developed to treat diabetes. Although there is a plethora of data supporting the benefits of various SGLT2 inhibitors in patients with diabetes, data comparing one drug vs another within the class are sparce. In this week’s installment of Talking Therapeutics, we discuss new data that attempt to address this unmet question.

Talking Point: A Stalemate

This provocative study used large health registries to emulate a hypothetical target trial comparing empagliflozin vs dapagliflozin initiation in patients with diabetes from 2014 through 2020. The primary outcome was a composite of myocardial infarction, ischemic stroke, heart failure, or cardiovascular death.

In a group of over 50 000 patients the adjusted 6-year absolute risk of major adverse cardiovascular event was not different between empagliflozin and dapagliflozin initiators (10.0% versus 10.0%; risk difference, 0.0% [95% CI, −0.9% to 1.0%]; risk ratio, 1.00 [95% CI, 0.91 to 1.11]). These results were consistent regardless of the presence of atherosclerotic heart disease and heart failure.

Talking Point: More Data Would Be Helpful

Given the overall similarity between the 2 drugs studied, it’s not overly surprising that no difference was identified. Still, given that there was a signal for difference when these 2 drugs were studied in a heart failure cohort, I think that a randomized trial comparing these two drugs would be very valuable.

Additionally, data comparing either empagliflozin or dapagliflozin to sotagliflozin would be very useful, given that sotagliflozin has a different mechanism of action and blocks both SGLT1 and SGLT2.