Diabetes mellitus (DM) is characterized by the appearance of progressive kidney damage, which may progress to end-stage kidney disease. The control of hyperglycemia is usually not sufficient to halt this progression. The kidney damage is quantitatively and qualitatively different in the two forms of diabetes; the typical nodular fibrosis (Kimmelstiel Wilson nodules) appears mostly in type 1 DM, whereas glomerulomegaly is primarily present in type 2 obese DM. An analysis of the different metabolites and hormones in type 1 and type 2 DM and their differential pharmacological treatments might be helpful to advance the hypotheses on the different histopathological patterns of the kidneys and their responses to sodium/glucose transporter type 2 inhibitors (SGLT2i).