Changes in plasma and urine metabolites associated with empagliflozin in patients with type 1 diabetes

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2021-11, Vol.23 (11), p.2466-2475
• Main Authors: Liu, Hongyan, Sridhar, Vikas S., Montemayor, Daniel, Lovblom, Leif Erik, Lytvyn, Yuliya, Ye, Hongping, Kim, Jiwan, Ali, Mir Tariq, Scarr, Daniel, Lawler, Patrick R., Perkins, Bruce A., Sharma, Kumar, Cherney, David Z. I.
• Format: Article
• Language: English
• Subjects: Alanine; Antidiabetics; Diabetes; Diabetes mellitus (insulin dependent); empagliflozin; Fatty acids; Glucose transporter; Hyperglycemia; Hypoxia; Kidney diseases; Metabolic pathways; Metabolism; Metabolites; metabolomics; Mitochondria; Oxidative stress; Plasma; Principal components analysis; SGLT2 inhibition; Tricarboxylic acid cycle; type 1 diabetes; Urine
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.14489

Aim To examine the impact of the sodium‐glucose co‐transporter‐2 inhibitor, empagliflozin, on plasma and urine metabolites in participants with type 1 diabetes. Material and Methods Participants (n = 40, 50% male, mean age 24.3 years) with type 1 diabetes and without overt evidence of diabetic kidney disease had baseline assessments performed under clamped euglycaemia and hyperglycaemia, on two consecutive days. Participants then proceeded to an 8‐week, open‐label treatment period with empagliflozin 25 mg/day, followed by repeat assessments under clamped euglycaemia and hyperglycaemia. Plasma and urine metabolites were first grouped into metabolic pathways using MetaboAnalyst software. Principal component analysis was performed to create a representative value for each sufficiently represented metabolic group (false discovery rate ≤ 0.1) for further analysis. Results Of the plasma metabolite groups, tricarboxylic acid (TCA) cycle (P