Effects of empagliflozin on lipoprotein subfractions in patients with type 2 diabetes: data from a randomized, placebo-controlled study. (August 2021)

• Record Type: Journal Article
• Authors: Rau, Matthias; Thiele, Kirsten; Korbinian Hartmann, Niels-Ulrik; Möllmann, Julia; Wied, Stephanie; Böhm, Michael; Scharnagl, Hubert; März, Winfried; Marx, Nikolaus; Lehrke, Michael
• Is Part Of: Atherosclerosis. Volume 330(2022)
• Page Start: 8
• Page End: 13
• Publication Date: 2021-08
• Subjects: Diabetes -- SGLT2 inhibitors -- Empagliflozin -- LDL cholesterol -- Lipoprotein subfractions -- LDL particle size; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2021.06.915
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Background and aims: Sodium-glucose cotransporter-2 inhibitors, glucose-lowering drugs that increase urinary glucose excretion, have been shown to reduce CV events in patients with type 2 diabetes (T2D), despite the fact that these agents increase blood levels of the proatherogenic low density lipoprotein cholesterol (LDL-C). It has been hypothesized that hemoconcentration due to osmotic diuresis, effects on calculated LDL particle size, or a modulation of lipoprotein subfractions may play a role in this context but to date the underlying mechanisms remain largely unexplored. Therefore, the present study examined effects of empagliflozin on LDL-C and lipoprotein subfractions including calculated LDL particle size and composition. Methods: In this placebo-controlled, randomized, double blind study, patients with T2D were randomized to empagliflozin 10 mg (n = 20) or placebo (n = 22). Composition of lipoprotein subfractions was assessed before and after 3 months of treatment. Lipoproteins were separated using a combined ultracentrifugation-precipitation method (β-quantification). Results: Empagliflozin increased LDL-C after 3 months of treatment (from baseline: 103 ± 36 mg/dL to 112 ± 47 mg/dL; p < 0.001) while no difference was recorded after day 1 or day 3 of treatment. The increase of LDL-C was paralleled by an increase of total cholesterol (baseline: 169 ± 41 mg/dL, 3 months: 185 ± 48 mg/dL; p = 0.001). Analyses of lipoprotein subfractions revealed LDL phospholipids and LDL apolipoprotein B to be increased by empagliflozin after 3 months of treatment while calculated LDL particle size was not affected. In addition empagliflozin increased free fatty acid concentrations. Conclusions: Empagliflozin treatment of patients with T2D increased LDL-C and LDL apolipoprotein B levels but had no effect on calculated LDL particle size. Graphical abstract: Image 1 Highlights: Empagliflozin leads to an increase of low density lipoprotein cholesterol (LDL-C), low density lipoprotein (LDL) subfractions and free fatty acids. Increase of LDL-C seems to be not attributable to hemoconcentration. Empagliflozin does not affect calculated LDL particle size and composition.