ArticleMetabolites2025
LC-MS-Based Untargeted Metabolic Profiling in Plasma Following Dapagliflozin Administration in Healthy Volunteers.
Article in Metabolites, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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9 authors.
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Abstract
Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, treats type 2 diabetes by blocking renal glucose reabsorption and promoting urinary glucose excretion. This mechanism lowers blood glucose concentrations independently of insulin. The resulting caloric loss also contributes to weight reduction. Although these effects are well documented in patients with diabetes, their magnitude and underlying mechanisms in healthy individuals remain poorly understood. BACKGROUND/
objectivesWe investigated metabolic alterations after a single 10 mg dose of dapagliflozin in healthy adults with normal body-mass indices (BMIs) using untargeted metabolomics.
methodsThirteen healthy volunteers completed this study. Plasma was collected before and 24 h after dosing. Untargeted metabolic profiling was performed with ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry.
resultsTwenty-five endogenous metabolites were annotated; ten were putatively identified. Eight metabolites increased significantly, whereas two decreased. Up-regulated metabolites included phosphatidylcholine (PC) species (PC O-36:5, PC 36:3), phosphatidylserine (PS) species (PS 40:2, PS 40:3, PS 36:1, PS 40:4), lysophosphatidylserine 22:1, and uridine. Dehydroepiandrosterone sulfate and bilirubin were down-regulated. According to the Human Metabolome Database, these metabolites participate in glycerophospholipid, branched-chain amino acid, pyrimidine, and steroid-hormone metabolism.
conclusionsDapagliflozin may affect pathways related to energy metabolism and homeostasis beyond glucose regulation. These data provide a reference for future investigations into energy balance and metabolic flexibility in metabolic disorders.
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