Abstract 15785: Effects of Empagliflozin on Fatty Acid Binding Protein 4 and Body Composition in Patients Without Diabetes but With Risk Factors for Adverse Cardiac Remodeling From the Empa-Heart 2 Cardiolink-7 Randomized Clinical Trial

Background: Prevention of the progression from stage B to C heart failure is an unmet need. Increased fat composition in skeletal muscle is one of the mechanisms associated with heart failure with preserved ejection fraction. Fatty acid binding protein 4 (FABP4) is known to facilitate the transport of fatty acid to tissue mitochondria for lipid oxidation. Knockdown of FABP4 gene is associated with increased body weight and fat mass in animal models. We sought to determine if Sodium-glucose co-transporter 2 (SGLT2) inhibition with empagliflozin leads to change in blood FABP4 levels and improvement in body composition in patients without diabetes and significant heart failure but with risk factors for adverse cardiac remodeling. Hypothesis: Empagliflozin increases blood FABP4 concentration and lowers body fat composition without changes in skeletal muscle mass. Methods: A total of 42 individuals between 40 and 80 years of age without diabetes but with risk factors for adverse cardiac remodeling were randomized to empagliflozin (10 mg/day; n=21) and placebo (n=21) groups for 6 months. Body composition parameters measured by bio-impedance analysis (InBody-720) included body weight (BW), skeletal muscle mass (SMM) and body fat mass (BFM) at baseline and 6 months follow up. Blood FABP4 concentrations were measured at the same time points. Results: There were no significant differences between two groups in baseline characteristics, BW, SMM, BFM, or FABP4. From baseline to 6 months, empagliflozin compared to placebo significantly increased blood FABP4 concentrations (6067.3 ± 7591.4 pg/ml vs 2714.9 ± 11232.6 pg/ml, p = 0.002), but decreased BW (-1.19 ± 1.01 kg vs 0.34 ± 2.59 kg, p = 0.018) and BFM (-0.68 ± 1.27 kg vs 0.53 ± 2.01 kg, p = 0.024). However, empagliflozin did not significantly affect changes in SMM from baseline to 6 months (-4.01 ± 0.70 kg vs -0.17 ± 0.96 kg, p = 0.387). Conclusions: SGLT2 inhibition with empagliflozin, in patients with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, increased blood FABP4 concentrations and ameliorated BW and body fat composition with no effect on skeletal muscle mass following 6 months of treatment.