Dapagliflozin is a member of a new class of medication called gliflozins indicated for the treatment of diabetes and has recently been also approved for the treatment of kidney and heart diseases. Gliflozins lower blood glucose levels by inhibition of the sodium glucose co-transporter 2 (SGLT2), which is predominantly expressed in the S1 segment of renal proximal tubules and responsible for >90% of renal glucose reabsorption. Renal and cardio protection by gliflozins cannot be solely explained by blood glucose lowering. To gain further mechanistic insights, we determined the metabolomic and proteomic signature of dapagliflozin in a murine model of diabetes. Male C57BL/6 non-diabetic wildtype and littermate Ins2 (Akita) diabetic mice, both fed a Western diet for 5 weeks, were given dapagliflozin (10 mg/kg diet) or vehicle for one week (4 groups, N=8/group). Blood and urine glucose levels confirmed the expected treatment response. We analyzed metabolome, proteome and phosphoproteome for a range of tissues (kidney, liver, heart, smooth muscle, white adipose tissue) and body fluids (serum, urine, erythrocytes), and extended the analysis to the gut metaproteome.