Carcinogenicity Risk Assessment Supports the Chronic Safety of Dapagliflozin, an Inhibitor of Sodium–Glucose Co-Transporter 2, in the Treatment of Type 2 Diabetes Mellitus

Table 2 Summary of 24-month oral carcinogenicity study with dapagliflozin in rats

Dapagliflozin dose (mg/kg per day):	Males					Females
Dapagliflozin dose (mg/kg per day):	0^a (n = 70)	0^b (n = 70)	0.5 (n = 70)	2 (n = 70)	10 (n = 70)	0^a (n = 70)	0^b (n = 70)	0.5 (n = 70)	2 (n = 70)	10 (n = 70)
C _max at day 184, μg/mL	NA	NA	0.38	1.29	8.05	NA	NA	0.50	1.84	8.84
AUC_(0–24) at day 184^c, μg h/mL	NA	NA	3.12	11.80	60.70	NA	NA	4.04	16.00	86.60
No. survivors at termination, n (%)	20 (29)	22 (31)	31 (44)	30 (43)	22 (31)	28 (40)	33 (47)	31 (44)	25 (36)	27 (39)
Major causes of death^d, %
Chronic progressive nephropathy	48	46	62	50	75	5	3	10	11	12
Mammary tumor	0	0	0	0	0	19	41	36	27	28
Pituitary tumor	4	2	3	0	2	33	30	10	18	21
Other causes	48	52	35	50	23	43	26	44	44	39

AUC _(0–24) area under the plasma concentration–time curve from administration to 24 h, C _max maximum observed plasma concentration, NA not applicable
^aVehicle-control group
^bWater-control group
^cTermination occurred in weeks 89–91 for males and weeks 105–106 for females
^dPercentage of deaths attributed to a specific cause