SGLT2 inhibitors improve kidney function and morphology by regulating renal metabolic reprogramming in mice with diabetic kidney disease.

Furthermore, we found that dihydroorotate levels were significantly increased, whereas the levels of its downstream metabolites were increased, including orotate (despite P = 0.052, it had an increasing trend, with VIP = 1.28 and FC = 1.45), uridine monophosphate (UMP), uracil dinucleotide (UDP) and cytidine monophosphate (CMP).

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In these significantly enriched pathways, the overall levels of metabolites in ‘glycine, serine and threonine metabolism’ (log2[FC] = 0.765) and ‘aminoacyl-tRNA biosynthesis’ (log2[FC] = 0.688) pathways showed a trend opposite to that of the db/db group after EMPA intervention (Figs. 4 E and 6 G).

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