Potential contribution of haemoconcentration to changes in lipid variables with empagliflozin in patients with type 2 diabetes: A post hoc analysis of pooled data from four phase 3 randomized clinical trials

AIM: To examine the association between changes in lipids and markers of haemoconcentration (haematocrit and serum albumin) with empagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, in patients with type 2 diabetes (T2D) using pooled data from four phase 3 randomized trials. MATERIALS AND METHODS: Patients with T2D received placebo (n = 825), empagliflozin 10 mg (n = 830) or 25 mg (n = 822) for 24 weeks. In post hoc mediation analyses, we assessed total changes in LDL‐cholesterol, HDL‐cholesterol, triglycerides, apolipoprotein (Apo) B, and Apo A‐I, and changes in these variables associated with, and independent of, changes in haematocrit and serum albumin at week 24 using ANCOVA models. RESULTS: Empagliflozin versus placebo increased serum LDL‐cholesterol, HDL‐cholesterol, and Apo A‐I, decreased triglycerides (empagliflozin 10 mg only), and (non‐significantly) increased Apo B. Empagliflozin modestly increased haematocrit and serum albumin. In mediation analyses, haematocrit changes (increases) with empagliflozin were associated with significant changes (increases) in all lipid variables, including Apo B. Except for triglycerides (non‐significant), similar lipid variable associations were observed with serum albumin changes. Haematocrit‐ and serum albumin‐independent changes in lipids with empagliflozin were significant for HDL‐cholesterol (increases), mostly significant for triglycerides (decreases), and less so for other lipid fractions. CONCLUSION: Haematocrit and serum albumin increases were associated with increases in lipid fractions with empagliflozin. Empagliflozin‐associated changes in serum lipids, particularly LDL‐cholesterol increases, may be partly attributable to haemoconcentration resulting from increased urinary volume and subsequent volume contraction.