1. Safety and tolerability
David Fitchett, MD
Cardiologist, St Michael’s Hospital Associate Professor of Medicine, University of Toronto, Toronto, Canada

2. Disclosures Consultations
Boehringer Ingelheim, Novo Nordisk, AstraZeneca, Sanofi, Merck

3. Adverse events Placebo (n=2333) Empagliflozin 10 mg (n=2345)
Rate
One or more AEs
2139 (91.7%)
178.67
2112 (90.1%)
150.34
2118 (90.4%)
148.36
One or more drug-related* AEs
549 (23.5%)
11.33
666 (28.4%)
14.15
643 (27.5%)
13.38
One or more AEs leading to discontinuation
453 (19.4%)
8.26
416 (17.7%)
7.28
397 (17.0%)
6.89
One or more serious AEs
988 (42.3%)
22.34
876 (37.4%)
18.20
913 (39.0%)
19.39
tlr-1245_0025final— Table : 1 Demographic data − treated set.
Rate = per100 patient-years
*As reported by the investigator Patients treated with ≥1 dose of study drug

4. Adverse events consistent with urinary tract infection
Placebo (n=2333)
Empagliflozin 10 mg (n=2345)
Empagliflozin
25 mg (n=2342)
n (%)
Rate
Events consistent with UTI
423 (18.1%)
8.21
426 (18.2%)
8.02
416 (17.8%)
7.75
Events leading to discontinuation 10
(0.4%)
0.17 22
(0.9%)
0.37 19
(0.8%)
0.31
By sex
Male
158 (9.4%)
3.96
180 (10.9%)
4.49
170 (10.1%)
4.09
Female
265 (40.6%)
22.81
246 (35.5%)
18.83
246 (37.3%)
20.38
Total: Table : 1
Rate = per100 patient-years
Patients treated with ≥1 dose of study drug
Based on 79 MedDRA preferred terms

5. Complicated urinary tract infection
Placebo (n=2333)
Empagliflozin 10 mg (n=2345)
Empagliflozin 25 mg (n=2342)
n (%)
Rate
Complicated urinary tract infection*
41 (1.8%)
0.71
34 (1.4%)
0.57
48 (2.0%)
0.80
Urinary tract infection
16 (0.7%)
0.28
13 (0.6%)
0.22
0.27
Pyelonephritis†
22 (0.9%)
0.38
15 (0.6%)
0.25
20 (0.9%)
0.33
Urosepsis
3 (0.1%)
0.05
6 (0.3%)
0.10
11 (0.5%)
0.18
Rate = per100 patient-years
Patients treated with ≥1 dose of study drug Events reported in >0.1% of patients in any group are shown *Pyelonephritis, urosepsis or serious adverse event consistent with urinary tract infection †Based on 15 MedDRA preferred terms

6. Adverse events consistent with genital infection
Placebo (n=2333)
Empagliflozin 10 mg (n=2345)
Empagliflozin 25 mg (n=2342)
n (%)
Rate
Events consistent with genital infection
42 (1.8%)
0.73
153 (6.5%)
2.66
148 (6.3%)
2.55
Serious events
3 (0.1%)
0.05
5 (0.2%)
0.08
4 (0.2%)
0.07
Events leading to discontinuation
2 (0.1%)
0.03
19 (0.8%)
0.32
14 (0.6%)
0.23
By sex
Male 25
(1.5%)
0.60
89 (5.4%)
2.16
77 (4.6%)
1.78
Female 17
(2.6%)
1.09 64
(9.2%)
3.93 71
(10.8%)
4.81
Overall: table : 1
Serious: table : 4
Leading to discontinuation: table : 5
Rate = per100 patient-years
Patients treated with ≥1 dose of study drug Based on 88 MedDRA preferred terms

7. Confirmed hypoglycaemic adverse events
Placebo (n=2333)
Empagliflozin 10 mg (n=2345)
Empagliflozin 25 mg (n=2342)
n (%)
Confirmed hypoglycaemic adverse events
650 (27.9%)
656 (28.0%)
647 (27.6%)
Events requiring assistance
36 (1.5%)
33 (1.4%)
30 (1.3%)
Patients taking insulin at baseline
Total
483 (42.6%)
494 (43.6%)
464 (41.4%)
28 (2.5%)
27 (2.4%)
25 (2.2%)
Overall n(%): table : 4
Requiring assistance n (%): table : 4
Patients treated with ≥1 dose of study drug Plasma glucose <3.9 mmol/L (70 mg/dL) and/or requiring assistance

8. Other adverse events (1)
Placebo (n=2333)
Empagliflozin
10 mg (n=2345)
Empagliflozin 25 mg (n=2342)
n (%)
Rate
Diabetic ketoacidosis* 1
(<0.1%)
0.02 3
(0.1%)
0.05
Acute kidney injury†
155
(6.6%)
2.77
121
(5.2%)
2.07
125
(5.3%)
2.12
Events consistent with volume depletion§
115
(4.9%)
2.04
1.97
124
2.11
Serious events 24
(1.0%)
0.42 19
(0.8%)
0.32 26
(1.1%)
0.43
Events leading to discontinuation 7
(0.3%)
0.12 4
(0.2%)
0.07
Venous thrombotic events** 20
(0.9%)
0.35 9
(0.4%)
0.15 21
Table : 1 (tir), n(%)
Rate = per100 patient-years
Patients treated with ≥1 dose of study drug *Based on 4 MedDRA preferred terms. †Based on 1 standardised MedDRA query §Based on 8 MedDRA preferred terms. **Based on 1 standardised MedDRA query

9. Other adverse events (2)
Placebo (n=2333)
Empagliflozin 10 mg (n=2345)
Empagliflozin 25 mg (n=2342)
n (%)
Rate
Hepatic injury*
108
(4.6%)
1.91 80
(3.4%)
1.35 88
(3.8%)
1.48
Hypersensitivity*
197
(8.4%)
3.59
158
(6.7%)
2.75
181
(7.7%)
3.14
Bone fractures† 91
(3.9%)
1.61 92
1.57 87
(3.7%)
1.46
Rate = per100 patient-years
Table : 1 (tir), n(%)
Patients treated with ≥1 dose of study drug *Based on standardised MedDRA queries †Based on 62 MedDRA preferred terms

10. Changes in clinical laboratory parameters
Electrolytes 
Sodium, mEq/L
141 (2)
0 (2)
Potassium, mEq/L
4.3 (0.4)
0.0 (0.4)
Calcium, mg/dL
9.7 (0.5)
0.0 (0.5)
9.7 (0.4)
Magnesium, mEq/L
1.7 (0.2)
0.0 (0.2)
0.1 (0.2)
Phosphate, mg/dL
3.7 (0.3)
0.0 (0.3)
0.1 (0.3)
Serum creatinine, mg/dL
1.04 (0.24)
0.07 (0.25)
1.03 (0.23)
0.04 (0.2)
1.04 (0.25)
0.04 (0.19)
eGFR mL/min/1.73m2  
74.8 (20.6)
-4.5 (12.9)
75.2 (21.1)
-2.5 (13.1)
75.0 (21.4)
-2.8 (13.4)
Placebo (n=2333)
Empagliflozin 10 mg (n=2345)
Empagliflozin 25 mg (n=2342)
Baseline
Change from baseline
Haematocrit, %
41.1 (5.7)
0.9 (4.7)
41.2 (5.6)
4.8 (5.5)
41.3 (5.7)
5.0 (5.3)
Haemoglobin, g/dL
13.4 (1.5)
-0.1 (1.2)
0.8 (1.3)
13.5 (1.5)
Data are mean (SD) in patients treated with ≥1 dose of study drug Changes from baseline are at last value on treatment, defined as the last measurement ≤3 days after the last intake of study drug