Effect of empagliflozin on plasma lipids and lipoproteins in type 2 diabetes and heart failure – Empire HF and SIMPLE

OBJECTIVE: Beyond glucose-lowering, sodium-glucose co-transporter 2 (SGLT2) inhibitors have cardioprotective effects with unclear mechanisms. We examined changes in an extensive panel of plasma lipids, lipoproteins, and apolipoproteins and whether these changes were independent of weight loss, hemoglobin A1c, and hematocrit in patients treated with empagliflozin vs placebo to better understand the observed cardioprotective effects. METHODS: Post-hoc analyses of 2 double-blind, placebo-controlled trials, the Empire HF trial including 190 patients with heart failure and reduced ejection fraction and the SIMPLE trial including 90 patients with type 2 diabetes randomized to, respectively, 10 mg and 25 mg empagliflozin daily or placebo for 12 weeks. RESULTS: In studies combined, empagliflozin reduced age and sex adjusted body weight by 1.40 kg (SEM: 0.10; P < .001) and hemoglobin A1c by 2.71 mmol/mol (SEM: 0.24; P < .001); and increased hematocrit by 1.9% (SEM: 0.12; P < .001) compared to placebo. No mean changes were seen in concentrations of total cholesterol, low-density lipoprotein (LDL) cholesterol, small dense LDL cholesterol, very low-density lipoprotein cholesterol, triglyceride rich lipoprotein cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, apolipoprotein B, lipoprotein(a), HDL cholesterol, and triglycerides adjusted for body weight, hemoglobin A1c, and hematocrit with empagliflozin compared to placebo. CONCLUSION: Empagliflozin treatment reduced body weight and hemoglobin A1c, and increased hematocrit. No changes were seen in concentrations of lipids and lipoproteins with empagliflozin compared to placebo. This suggests that the cardioprotective effects of SGLT2 inhibitors are independent of lipid and lipoprotein concentrations.