Table 2 Adverse events in the Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58), CANagliflozin CardioVascular Assessment Study (CANVAS) Program, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose (EMPA–REG OUTCOME), and Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trials

Male genital infection^b

76 (0.9)

9 (0.1)

+^c

8.36 (4.19–16.68)^c

0.001^c

34.9

10.8

+^c

< 0.001^c

166 (5.0)

25 (1.5)

+^c

< 0.001^c

28 (0.2)

3 (0.0)

8.4

0.9

+^c

9.30 (2.83–30.60)^c

Female genital infection^b

68.8

17.5

+^c

< 0.001^c

135 (10.0)

17 (2.6)

+^c

< 0.001^c

22 (0.3)

10 (0.0)

12.6

6.1

+

2.10 (1.00–4.45)

Any AE

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

N/A

4230 (90.2)

2139 (91.7)

−^c

< 0.001^c

1784 (8.1)

1860 (0.8)

351.4

379.3

−^c

0.87 (0.82–0.93)^c

Serious AE

2925 (34.1)

3100 (36.2)

−^c

0.91 (0.87–0.96)^c

< 0.001^c

104.3

120

−^c

0.04^c

1789 (38.2)

988 (42.3)

−^c

< 0.001^c

737 (3.3)

806 (0.4)

145.2

164.4

−^c

0.87 (0.79–0.97)^c

AE leading to discontinuation

693 (8.1)

592 (6.9)

+^c

1.15 (1.03–1.28)^c

0.01^c

35.5

32.8

+

0.07

813 (17.3)

453 (19.4)

−^c

< 0.001^c

N/A

N/A

N/A

N/A

N/A

N/A

Hypoglycemia

58 (0.7)

83 (1.0)

−^c

0.68 (0.49–0.95)^c

0.02^c

50

46.4

+

0.20

1303 (27.8)

650 (27.9)

−

N/A

225 (1.0)

240 (0.1)

44.3

48.9

−

0.92 (0.77–1.11)

UTI

127 (1.5)

133 (1.6)

−

0.93 (0.73–1.18)

0.54

40

37

+

0.38

842 (18.0)

423 (18.1)

−

N/A

245 (1.1)

221 (0.1)

48.3

45.1

+

1.08 (0.90–1.29)

Fracture

457 (5.3)

440 (5.1)

+

1.04 (0.91–1.18)

0.59

15.4

11.9

+^c

0.02^c

179 (3.8)

91 (3.9)

−

N/A

67 (0.3)

68 (0.0)

11.8

12.1

−

0.98 (0.70–1.37)

Hyperkalemia

N/A

N/A

N/A

N/A

N/A

6.9

4.4

+

0.10

N/A

N/A

N/A

N/A

151

181

29.7

36.9

−

0.80

Amputation

123 (1.4)

113 (1.3)

+

1.09 (0.84–1.40)

0.53

6.3

3.4

+^c

< 0.001^c

N/A

N/A

N/A

N/A

70 (0.3)

63 (0.0)

12.3

11.2

+

1.11 (0.79–1.56)

AKI

125 (1.5)

113 (1.3)

−^c

0.69 (0.55–0.87)^c

0.002^c

3

4.1

−

0.33

45 (1.0)

37 (1.6)

−^c

< 0.05^c

86 (0.4)

98 (0.0)

16.9

20

−

0.85 (0.64–1.13)

Breast cancer

36 (0.4)

113 (1.3)

0

1.02 (0.64–1.63)

0.92

3.1

2.6

+

0.65

N/A

N/A

N/A

N/A

8 (0.1)

3 (0.0)

4.1

1.6

+

2.59 (0.69–9.76)

Bladder cancer

26 (0.3)

45 (0.5)

−^c

0.57 (0.35–0.93)^c

0.02^c

1

1.1

−

0.74

N/A

N/A

N/A

N/A

10 (0.0)

9 (0.0)

1.7

1.6

+

1.10 (0.45–2.72)

DKA

27 (0.3)

12 (0.1)

+^c

2.18 (1.10–4.30)^c

0.02^c

0.6

0.3

+

0.14

4 (0.1)

1 (<  0.1)

+

N/A

11 (0.0)

1 (0.0)

2.2

0.2

+^c

10.80 (1.39–83.65)^c