Empagliflozin exerts null effect on myocardial reserve flow in T2DM

Empagliflozin falls short of improving myocardial reserve flow in type 2 diabetes mellitus (T2DM) patients at high risk of cardiovascular disease, according to data from the SIMPLE trial*.

SIMPLE randomized 90 patients (80 percent male, mean HbA1c 7.6 percent, mean blood pressure 139/81 mm Hg) to receive either empagliflozin 25 mg (n=45) or placebo (n=45) once daily for 13 weeks. Treatment was given in addition to standard therapy.

Half of the population (51 percent) had a history of coronary disease, defined as either previous myocardial infarction, significant stenosis of a coronary artery, or coronary artery bypass graft. Baseline myocardial flow reserve (MFR) values were normal in 29 patients, in the intermediate range in 22, and impaired in 36. Mean left ventricular ejection fraction was 58 percent. T2DM was well controlled. 

Mean MFR at baseline was 2.21 (95 percent confidence interval [CI], 2.08–2.35). At week 13, the primary outcome of change in MFR, as quantified by Rubidium‐82 positron emission tomography/computed tomography, was not significant in either the empagliflozin or the placebo group (0.01 vs 0.06; difference, −0.05, 95 percent CI, −0.33 to 0.23).

Moreover, empagliflozin conferred no effects on the secondary outcomes, such as resting rate‐pressure product adjusted MFR, changes in myocardial flow during rest and stress, and reversible cardiac ischaemia parameters.

Compared with placebo, treatment with empagliflozin yielded a 0.76-percent reduction in HbA1c (p<0.001) and a 1.69-percent increase in haematocrit (p<0.001).

The findings challenge the notion that a short‐term improvement in MFR explains the reduction in cardiovascular events observed in the outcome trials.

*The Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus