Download Introduction - Diabetes In Control

Safety and tolerability
David Fitchett, MD
Cardiologist, St Michael’s Hospital
Associate Professor of Medicine, University of Toronto,
Toronto, Canada
1
Disclosures
• Consultations
– Boehringer Ingelheim, Novo Nordisk, AstraZeneca, Sanofi, Merck
2
Adverse events
Placebo
(n=2333)
Empagliflozin
10 mg
(n=2345)
Empagliflozin
25 mg
(n=2342)
n (%)
Rate
n (%)
Rate
n (%)
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
Rate = per100 patient-years
*As reported by the investigator
Patients treated with ≥1 dose of study drug
3
Adverse events consistent with urinary tract
infection
Placebo
(n=2333)
Empagliflozin
10 mg
(n=2345)
Empagliflozin
25 mg
(n=2342)
n (%)
Rate
n (%)
Rate
n (%)
Rate
423
(18.1%)
8.21
426
(18.2%)
8.02
416
(17.8%)
7.75
10
(0.4%)
0.17
22
(0.9%)
0.37
19
(0.8%)
0.31
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
Events consistent with UTI
Events leading to
discontinuation
By sex
Rate = per100 patient-years
Patients treated with ≥1 dose of study drug
Based on 79 MedDRA preferred terms
4
Complicated urinary tract infection
Placebo
(n=2333)
Empagliflozin
10 mg
(n=2345)
Empagliflozin
25 mg
(n=2342)
n (%)
Rate
n (%)
Rate
n (%)
Rate
41
(1.8%)
0.71
34
(1.4%)
0.57
48
(2.0%)
0.80
16
(0.7%)
0.28
13
(0.6%)
0.22
16
(0.7%)
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
Complicated urinary tract
infection*
Urinary tract infection
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
5
Adverse events consistent with genital infection
Placebo
(n=2333)
Empagliflozin
10 mg
(n=2345)
Empagliflozin
25 mg
(n=2342)
n (%)
Rate
n (%)
Rate
n (%)
Rate
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
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
Events consistent with
genital infection
By sex
Rate = per100 patient-years
Patients treated with ≥1 dose of study drug
Based on 88 MedDRA preferred terms
6
Confirmed hypoglycaemic adverse events
Placebo
(n=2333)
Empagliflozin
10 mg
(n=2345)
Empagliflozin
25 mg
(n=2342)
n (%)
Confirmed hypoglycaemic
adverse events
Events requiring
assistance
650 (27.9%)
656 (28.0%)
647 (27.6%)
36 (1.5%)
33 (1.4%)
30 (1.3%)
483 (42.6%)
494 (43.6%)
464 (41.4%)
28 (2.5%)
27 (2.4%)
25 (2.2%)
Patients taking insulin at
baseline
Total
Events requiring
assistance
Patients treated with ≥1 dose of study drug
Plasma glucose <3.9 mmol/L (70 mg/dL) and/or requiring assistance
7
Other adverse events (1)
Placebo
(n=2333)
Empagliflozin
10 mg
(n=2345)
Empagliflozin
25 mg
(n=2342)
n (%)
Rate
n (%)
Rate
n (%)
Rate
1
(<0.1%)
0.02
3
(0.1%)
0.05
1
(<0.1%)
0.02
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
115
(4.9%)
1.97
124
(5.3%)
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
1
(<0.1%)
0.02
4
(0.2%)
0.07
20
(0.9%)
0.35
9
(0.4%)
0.15
21
(0.9%)
0.35
Diabetic ketoacidosis*
Venous thrombotic events**
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
8
Other adverse events (2)
Placebo
(n=2333)
Empagliflozin
10 mg
(n=2345)
Empagliflozin
25 mg
(n=2342)
n (%)
Rate
n (%)
Rate
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
(3.9%)
1.57
87
(3.7%)
1.46
Rate = per100 patient-years
Patients treated with ≥1 dose of study drug
*Based on standardised MedDRA queries
†Based on 62 MedDRA preferred terms
9
Changes in clinical laboratory parameters
Placebo
(n=2333)
Empagliflozin 10 mg
(n=2345)
Empagliflozin 25 mg
(n=2342)
Baseline
Change
from
baseline
Baseline
Change
from
baseline
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)
13.4 (1.5)
0.8 (1.3)
13.5 (1.5)
0.8 (1.3)
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)
74.8 (20.6)
-4.5 (12.9)
75.2 (21.1)
-2.5 (13.1)
75.0 (21.4)
-2.8 (13.4)
Sodium, mEq/L
141 (2)
0 (2)
141 (2)
0 (2)
141 (2)
0 (2)
Potassium, mEq/L
4.3 (0.4)
0.0 (0.4)
4.3 (0.4)
0.0 (0.4)
4.3 (0.4)
0.0 (0.4)
Calcium, mg/dL
9.7 (0.5)
0.0 (0.5)
9.7 (0.4)
0.0 (0.5)
9.7 (0.4)
0.0 (0.5)
Magnesium, mEq/L
1.7 (0.2)
0.0 (0.2)
1.7 (0.2)
0.1 (0.2)
1.7 (0.2)
0.1 (0.2)
Phosphate, mg/dL
3.7 (0.3)
0.0 (0.3)
3.7 (0.3)
0.1 (0.3)
3.7 (0.3)
0.1 (0.3)
eGFR mL/min/1.73m2
Electrolytes
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
10