Hyeon ji Kim (경북대학교)

Young-Ran Yoon (경북대학교)

Hyeon ji Kim (경북대학교)

Mi-Ri Gwon (경북대학교)

Hae Won Lee (경북대학교병원)

Sook Jin Seong (경북대학교병원)

Young-Ran Yoon (경북대학교)

Dapagliflozin, a sodium-glucose transporter 2 inhibitor, reduces blood glucose levels by inhibiting the reabsorption of filtered glucose in the proximal tubule of the kidneys. Additionally, it induces weight loss while providing glycemic control. Due to these effects, it is anticipated that dapagliflozin will impact lipid metabolism. Nevertheless, there is a scarcity of studies investigating alterations in lipid metabolites following dapagliflozin administration. This study aimed to explore the alterations in lipid metabolites after dapagliflozin administration.

In this study, a single dose of dapagliflozin (10 mg/day) was administered to 13 healthy volunteers with a body mass index of 18.0 to 25.0 kg/m². Plasma samples were collected before and after the single dose administration and analyzed using ultra high-performance liquid chromatography and quadrupole time-of-flight/mass spectrometer for untargeted metabolomics. Multivariate analysis and permutation tests were conducted. Metabolites with variable importance in projection values ≥1.0 and a p-value <0.05 were considered as putative metabolites.

The orthogonal partial least squares-discriminant analysis showed separation between the samples taken before and after administration. Thirteen metabolites were putatively identified: bilirubin, phosphatidylcholine (PC) O-36:5, fatty alcohol 18:4, PC 36:4, PC 36:3, PC 36:5, leucine, uridine, dehydroisoandrosterone sulfate, phosphatidylserine (PS) 18:2_22:0, PS 18:2_22:1, PS 8:0_28:1, and lysophosphatidylserine 22:1. Bilirubin and dehydroisoandrosterone sulfate decreased, while the others increased after the dapagliflozin administration.

This study observed a significant increase in metabolites associated with fatty acid metabolism after dapagliflozin administration, including fatty acyls and the ketogenic amino acid leucine. These findings suggest that the administration of dapagliflozin leads to a decrease in blood glucose levels and a reduction in the availability of glucose as an energy source. Consequently, the utilization of fatty acids and ketone bodies increases, making lipid metabolism the primary energy source. However, research with long-term dapagliflozin administration is needed to comprehensively understand the lipid metabolism changes induced by dapagliflozin.