98-LB: Effects of SGLT2 Inhibition on Skeletal Muscle Bioenergetics and Myocellular Lipids in Patients with T2D and HFrEF Free

Background: The CV benefits of SGLT2i are well established. However, how skeletal muscle (SkM) bioenergetics respond to SGLT2i in T2D and HFrEF remains largely unknown.

Objective: To explore the effects of empagliflozin on SkM bioenergetics (phosphorus metabolites & myocellular lipid content) at rest and post-exercise (³¹P & ¹H MRS) and cardiac function (MRI). Methods: Subjects with T2D & HFrEF (<40%) (n=6) were randomized 2:1 to empagliflozin 25mg (SGLT2i) or placebo for 12 wks (Age=59±2.6, BMI=33.3±1.1, A1c=7.1±0.3, EF 28±4%). A cardiac MRI, & static/dynamic ³¹P & ¹H SkM by MRS, were performed before & after treatment.

Results: In the empagliflozin group, SkM ³¹P MRS at rest, showed decrease in phosphodiesterase [PDE]. ³¹P MRS post-exercise, showed significant improvement in Phosphocreatinine (PCr) recovery, expressed by the K value. ¹H MRS showed a reduction of saturated intramyocellular lipids (IMCL-CH2:CH3 ratio).

Conclusion: Empagliflozin in subjects with T2D and HFrEF had beneficial effects in SkM energy utilization and muscle recovery post-exercise as determined by a decrease in PDE and increase in K value. Additionally, empagliflozin decreased saturated IMCL, which could be expected to improve mitochondrial function and energy utilization. If similar findings were to occur in cardiac muscle, this could provide a novel mechanism for the beneficial CV effects of SGLT2i.

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