Effect of empagliflozin on plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with type 2 diabetes

Aim: Cardiovascular benefits of sodium-glucose cotrasporter-2 (SGLT2) inhibitors occur despite a modest in-crease in low-density lipoprotein cholesterol (LDL-c). We tested whether the effects of chronic SGLT2 inhibition on lipid profile composition are mediated by elevation in plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels inhibiting LDL clearance.Methods: 78 patients with type 2 diabetes (T2D) received empagliflozin 25 mg/d in an open-label design. At enrollment and after 4-week therapy, fasting blood samples were collected for the measurement of plasma PCSK9, glucose, total and fractional cholesterol, and triglycerides.Results: Plasma PCSK9 was not significantly affected by empagliflozin (-10.7 [-24.1, 2.7] ng/mL). The treat-ment induced a mild increase in high-density lipoprotein cholesterol (+1.7 [0.5, 3.0] mg/dL), without significant LDL-c alterations (+1.0 [-4.1, 6.0] mg/dl). Changes in LDL-c were associated with changes in fasting glucose levels (beta = 0.320, p = 0.017), but not with plasma PCSK9 (beta = 0.010, p = 0.800), after adjustment for age, sex, baseline LDL-c, and body weight change.Conclusion: In patients with T2D, chronic SGLT2 inhibition with empagliflozin has no potentially harmful effects on circulating PCSK9 levels. This finding does not support a pathogenetic role of plasma PCSK9 in the mild plasma lipid alterations observed during SGLT2i treatment.