Why carry out this study?
|
Empagliflozin is a potent sodium-glucose co-transporter-2 (SGLT2) inhibitor indicated for the treatment of type 2 diabetes mellitus (T2DM), including reduction of cardiovascular (CV) mortality in patients with T2DM and CV disease. |
The clinical efficacy and safety profile of empagliflozin in T2DM has been well documented; however, new safety signals of increased lower limb amputations and fractures reported for another SGLT2 inhibitor have prompted a review of the risks associated with this drug class. |
This study examined the safety and tolerability of empagliflozin in patients with T2DM using data pooled from 20 placebo-controlled clinical trials based on over 16,480 patient-years’ exposure to empagliflozin. |
What was learned from the study?
|
This updated pooled analysis confirmed that both empagliflozin 10 mg and 25 mg are well tolerated in patients with T2DM. |
These results reinforce the findings of a favorable benefit–risk profile for empagliflozin from previous clinical trials in patients with T2DM, including trials establishing the effects of empagliflozin on CV and all-cause mortality. |
Introduction
Methods
Patients
ClinicalTrials.gov identifier (BI study number) | Short title | Treatment duration | Dose escalationa |
---|---|---|---|
NCT00558571 (1245.4) | 4 weeks’ treatment in patients with T2DM | 28 days | No |
NCT00789035 (1245.9) | Dose finder versus placebo as monotherapy | 12 weeks | No |
NCT00749190 (1245.10) | Dose finder versus placebo as add-on therapy | 12 weeks | No |
NCT00885118 (1245.15) | Treatment of patients with T2DM in Japan | 4 weeks | No |
NCT01210001 (1245.19) | Efficacy on background TZD ± metformin | 24 weeks | No |
NCT01177813 (1245.20) | Efficacy in drug-naïve patients | 24 weeks | No |
NCT01159600 (metformin) (1245.23) | Efficacy on background metformin | 24 weeks | No |
NCT01159600 (metformin + SU) (1245.23) | Efficacy on background metformin ± SU | 24 weeks | No |
NCT01131676 (1245.25) | Safety cardiovascular outcome trial | Mean: 2.8 years | No |
NCT02182830 (1245.29) | African American patients with T2DM and hypertension | 24 weeks | Yes |
NCT01011868 (1245.33) | Efficacy on background basal insulin | 78 weeks | No |
NCT01947855 (1245.35) | Japanese post-prandial glucose | 4 weeks | No |
NCT01164501 (1245.36) | Renal safety study | 52 weeks | No |
NCT01193218 (1245.38) | Japanese dose finder study plus extension | 52 weeks | No |
NCT01370005 (1245.48) | Efficacy in patients with T2DM and hypertension | 12 weeks | No |
NCT01306214 (1245.49) | Efficacy on background MDI insulin ± metformin | 52 weeks | No |
NCT02589639 (1245.107) | Empagliflozin add-on to insulin (Japan) | 52 weeks | No |
NCT01734785 (1275.9) | Empagliflozin add-on to linagliptin | 24 weeks | No |
NCT02453555 (1275.19) | Empagliflozin add-on to linagliptin (Japan) | 52 weeks | Yes |
NCT01649297 (1276.10) | Empagliflozin QD versus BID on background metformin | 16 weeks | No |
Assessments and Data Analyses
Results
Patient Disposition, Exposure and Baseline Characteristics
Placebo (n = 4904) | EMPA 10 mg (n = 4858) | EMPA 25 mg (n = 5057) | EMPA 10/25 mg (n = 10,177) | |
---|---|---|---|---|
Male, n (%) | 3119 (63.6) | 3094 (63.7) | 3249 (64.2) | 6529 (64.2) |
Age, years | 60.5 (9.8) | 60.3 (9.7) | 60.4 (9.8) | 60.3 (9.7) |
Age groups, years (%) | ||||
< 65 | 3197 (65.2) | 3168 (65.2) | 3293 (65.1) | 6639 (65.2) |
65 to < 75 | 1377 (28.1) | 1390 (28.6) | 1426 (28.2) | 2887 (28.4) |
75 to < 85 | 318 (6.5) | 290 (6.0) | 327 (6.5) | 630 (6.2) |
≥ 85 | 12 (0.2) | 10 (0.2) | 11 (0.2) | 21 (0.2) |
Race, n (%) | ||||
White | 3044 (62.1) | 3256 (67.0) | 3346 (66.2) | 6602 (64.9) |
Asian | 1347 (27.5) | 1252 (25.8) | 1349 (26.7) | 2601 (25.6) |
Black/African–American | 279 (5.7) | 213 (4.4) | 219 (4.3) | 512 (5.0) |
Othera | 51 (1.0) | 50 (1.0) | 51 (1.0) | 101 (1.0) |
Missing | 183 (3.7) | 87 (1.8) | 92 (1.8) | 361 (3.5) |
Region, n (%) | ||||
Europe | 1821 (37.1) | 1939 (39.9) | 2013 (39.8) | 3952 (38.8) |
North America | 1057 (21.6) | 1056 (21.7) | 1083 (21.4) | 2219 (21.8) |
Latin America | 474 (9.7) | 503 (10.4) | 505 (10.0) | 1008 (9.9) |
Africa/Middle East | 132 (2.7) | 129 (2.7) | 141 (2.8) | 270 (2.7) |
Asia | 1420 (29.0) | 1231 (25.3) | 1315 (26.0) | 2728 (26.8) |
Time since diabetes diagnosis, years, n (%) | ||||
≤ 1 | 259 (5.3) | 295 (6.1) | 308 (6.1) | 616 (6.1) |
> 1 to ≤ 5 | 1077 (22.0) | 1048 (21.6) | 1100 (21.8) | 2216 (21.8) |
> 5 | 3553 (72.5) | 3500 (72.0) | 3633 (71.8) | 7314 (71.9) |
Missing | 15 (0.3) | 15 (0.3) | 16 (0.3) | 31 (0.3) |
BMI, kg/m2b | 30.4 (5.5) | 30.5 (5.5) | 30.5 (5.5) | 30.5 (5.6) |
eGFR, ml/min/1.73 m2, n (%)c | ||||
≥ 90 | 1933 (39.4) | 1998 (41.1) | 2041 (40.4) | 4177 (41.0) |
≥ 60 to < 90 | 2123 (43.3) | 2203 (45.3) | 2155 (42.6) | 4477 (44.0) |
≥ 45 to < 60 | 519 (10.6) | 464 (9.6) | 535 (10.6) | 1003 (9.9) |
≥ 30 to < 45 | 277 (5.6) | 182 (3.7) | 262 (5.2) | 445 (4.4) |
< 30 | 52 (1.1) | 10 (0.2) | 61 (1.2) | 71 (0.7) |
Missing | 0 | 1 (< 0.1) | 3 (0.1) | 4 (< 0.1) |
General Safety
Placebo (n = 4904) | EMPA 10 mg (n = 4858) | EMPA 25 mg (n = 5057) | EMPA 10/25 mg (n = 10,177) | |
---|---|---|---|---|
≥ 1 AE | 197.62 | 170.01 | 168.59 | 168.89 |
≥ 1 drug-related AEa | 15.45 | 19.57 | 19.38 | 19.54 |
≥ 1 AE leading to discontinuation | 7.40 | 6.57 | 6.38 | 6.43 |
≥ 1 severe AEb | 10.43 | 8.80 | 9.51 | 9.04 |
≥ 1 serious AEc | 18.61 | 15.29 | 16.07 | 15.52 |
Fatal | 1.57 | 1.24 | 1.01 | 1.12 |
Placebo (n = 4904) | EMPA 10 mg (n = 4858) | EMPA 25 mg (n = 5057) | EMPA 10/25 mg (n = 10,177) | |
---|---|---|---|---|
≥ 1 AE | 3942 (80.4) | 3740 (77.0) | 3896 (77.0) | 7805 (76.7) |
≥ 1 drug-related AEa | 1028 (21.0) | 1247 (25.7) | 1279 (25.3) | 2571 (25.3) |
≥ 1 AE leading to discontinuation | 565 (11.5) | 514 (10.6) | 512 (10.1) | 1033 (10.2) |
≥ 1 severe AEb | 747 (15.2) | 651 (13.4) | 718 (14.2) | 1371 (13.5) |
≥ 1 serious AEc | 1204 (24.6) | 1046 (21.5) | 1104 (21.8) | 2161 (21.2) |
Fatal | 125 (2.5) | 101 (2.1) | 84 (1.7) | 186 (1.8) |
Immediately life-threatening | 53 (1.1) | 54 (1.1) | 64 (1.3) | 118 (1.2) |
Disability/incapacitation | 29 (0.6) | 20 (0.4) | 27 (0.5) | 47 (0.5) |
Requiring hospitalization | 1044 (21.3) | 898 (18.5) | 986 (19.5) | 1891 (18.6) |
Prolonged hospitalization | 79 (1.6) | 57 (1.2) | 76 (1.5) | 133 (1.3) |
Congenital anomaly | 0 | 0 | 0 | 0 |
Other | 193 (3.9) | 170 (3.5) | 175 (3.5) | 348 (3.4) |
Placebo (n = 4904) | EMPA 10 mg (n = 4858) | EMPA 25 mg (n = 5057) | EMPA 10/25 mg (n = 10,177) | |
---|---|---|---|---|
Number of patients | 1044 (21.3) | 898 (18.5) | 986 (19.5) | 1891 (18.6) |
SOC | ||||
Infections and infestations | 225 (4.6) | 187 (3.8) | 200 (4.0) | 387 (3.8) |
Neoplasms benign, malignant and unspecified (incl. cysts and polyps) | 45 (0.9) | 65 (1.3) | 75 (1.5) | 142 (1.4) |
Blood and lymphatic system disorders | 18 (0.4) | 16 (0.3) | 14 (0.3) | 30 (0.3) |
Immune system disorders | 4 (0.1) | 3 (0.1) | 4 (0.1) | 7 (0.1) |
Endocrine disorders | 3 (0.1) | 3 (0.1) | 8 (0.2) | 11 (0.1) |
Metabolism and nutrition disorders | 66 (1.3) | 42 (0.9) | 40 (0.8) | 82 (0.8) |
Psychiatric disorders | 19 (0.4) | 11 (0.2) | 7 (0.1) | 18 (0.2) |
Nervous system disorders | 152 (3.1) | 136 (2.8) | 153 (3.0) | 289 (2.8) |
Eye disorders | 26 (0.5) | 29 (0.6) | 22 (0.4) | 51 (0.5) |
Ear and labyrinth disorders | 17 (0.3) | 7 (0.1) | 16 (0.3) | 23 (0.2) |
Cardiac disorders | 347 (7.1) | 282 (5.8) | 296 (5.9) | 580 (5.7) |
Vascular disorders | 115 (2.3) | 74 (1.5) | 109 (2.2) | 183 (1.8) |
Respiratory, thoracic and mediastinal disorders | 69 (1.4) | 43 (0.9) | 52 (1.0) | 95 (0.9) |
Gastrointestinal disorders | 93 (1.9) | 94 (1.9) | 93 (1.8) | 187 (1.8) |
Hepatobiliary disorders | 25 (0.5) | 28 (0.6) | 30 (0.6) | 59 (0.6) |
Skin and subcutaneous tissue disorders | 28 (0.6) | 20 (0.4) | 34 (0.7) | 54 (0.5) |
Musculoskeletal and connective tissue disorders | 98 (2.0) | 79 (1.6) | 81 (1.6) | 160 (1.6) |
Renal and urinary disorders | 69 (1.4) | 43 (0.9) | 41 (0.8) | 84 (0.8) |
Pregnancy, puerperium and perinatal conditions | 0 | 0 | 1 (< 0.1) | 1 (< 0.1) |
Reproductive system and breast disorders | 10 (0.2) | 18 (0.4) | 19 (0.4) | 37 (0.4) |
Congenital, familial and genetic disorders | 6 (0.1) | 4 (0.1) | 2 (< 0.1) | 6 (0.1) |
General disorders and administration site conditions | 75 (1.5) | 58 (1.2) | 62 (1.2) | 121 (1.2) |
Investigations | 18 (0.4) | 8 (0.2) | 15 (0.3) | 23 (0.2) |
Injury, poisoning and procedural complications | 83 (1.7) | 69 (1.4) | 80 (1.6) | 151 (1.5) |
Surgical and medical procedures | 15 (0.3) | 14 (0.3) | 16 (0.3) | 30 (0.3) |
Social circumstances | 0 | 1 (< 0.1) | 0 | 1 (< 0.1) |
Product issues | 4 (0.1) | 0 | 2 (< 0.1) | 2 (< 0.1) |
Safety Topics of Interest
Hypoglycemia
Placebo (n = 4904) | EMPA 10 mg (n = 4858) | EMPA 25 mg (n = 5057) | EMPA 10/25 mg (n = 10,177) | |||||
---|---|---|---|---|---|---|---|---|
n (%) or n/N (%) | Rate/100 pt-yrs | n (%) or n/N (%) | Rate/100 pt-yrs | n (%) or n/N (%) | Rate/100 pt-yrs | n (%) or n/N (%) | Rate/100 pt-yrs | |
UTIs (BIcMQ) | 691 (14.1) | 9.70 | 684 (14.1) | 9.45 | 675 (13.3) | 9.04 | 1382 (13.6) | 9.27 |
Sex | ||||||||
Male | 204/3119 (6.5) | 3.97 | 225/3094 (7.3) | 4.33 | 224/3249 (6.9) | 4.11 | 455/6529 (7.0) | 4.21 |
Female | 487/1785 (27.3) | 24.50 | 459/1764 (26.0) | 22.43 | 451/1808 (24.9) | 22.35 | 927/3648 (25.4) | 22.55 |
Age, years | ||||||||
< 65 | 401/3197 (12.5) | 9.00 | 389/3168 (12.3) | 8.58 | 360/3293 (10.9) | 7.71 | 762/6639 (11.5) | 8.16 |
65 to < 75 | 220/1377 (16.0) | 10.35 | 216/1390 (15.5) | 9.64 | 243/1426 (17.0) | 10.59 | 466/2887 (16.1) | 10.14 |
75 to < 85 | 69/318 (21.7) | 13.39 | 79/290 (27.2) | 17.38 | 71/327 (21.7) | 14.72 | 153/630 (24.3) | 16.13 |
≥ 85 | 1/12 (8.3) | 4.61 | 0/10 | – | 1/11 (9.1) | 4.48 | 1/21 (4.8) | 2.98 |
Complicated UTIs (BIcMQ) | 59 (1.2) | 0.75 | 39 (0.8) | 0.48 | 54 (1.1) | 0.65 | 93 (0.9) | 0.56 |
Genital infections (BIcMQ) | 75 (1.5) | 0.95 | 278 (5.7) | 3.57 | 281 (5.6) | 3.52 | 565 (5.6) | 3.54 |
Sex | ||||||||
Male | 35/3119 (1.1) | 0.66 | 139/3094 (4.5) | 2.62 | 116/3249 (3.6) | 2.07 | 255/6529 (3.9) | 2.30 |
Female | 40/1785 (2.2) | 1.58 | 139/1764 (7.9) | 5.61 | 165/1808 (9.1) | 6.98 | 310/3648 (8.5) | 6.33 |
Age, years | ||||||||
< 65 | 50/3197 (1.6) | 1.03 | 192/3168 (6.1) | 4.01 | 192/3293 (5.8) | 3.93 | 386/6639 (5.8) | 3.93 |
65 to < 75 | 21/1377 (1.5) | 0.88 | 69/1390 (5.0) | 2.81 | 71/1426 (5.0) | 2.82 | 144/2887 (5.0) | 2.86 |
75 to < 85 | 4/318 (1.3) | 0.68 | 17/290
(5.9) | 3.21 | 17/327 (5.2) | 3.13 | 34/630 (5.4) | 3.13 |
≥ 85 | 0/12 | – | 0/10 | – | 1/11 (9.1) | 4.35 | 1/21 (4.8) | 2.92 |
Complicated genital infections (BIcMQ) | 24 (0.5) | 0.30 | 29 (0.6) | 0.36 | 26 (0.5) | 0.31 | 55 (0.5) | 0.33 |
Hypoglycemia (narrow SMQ) | 1045 (21.3) | 16.32 | 1009 (20.8) | 15.79 | 1053 (20.8) | 16.02 | 2067 (20.3) | 15.69 |
Confirmed hypoglycemic AEs | 987 (20.1) | 945 (19.5) | 1000 (19.8) | 1948 (19.1) | ||||
Confirmed hypoglycemiaa with baseline use of insulin and/or SU | 915 (30.2) | 20.36 | 889 (31.9) | 20.92 | 942 (31.2) | 20.84 | 1,833 (31.5) | 20.88 |
Confirmed hypoglycemia without baseline use of insulin and/or SU | 54 (2.9) | 2.66 | 38 (1.8) | 1.67 | 46 (2.3) | 2.13 | 85 (2.0) | 1.83 |
Diabetic ketoacidosis (narrow BIcMQb) | 4 (0.1) | 0.05 | 4 (0.1) | 0.05 | 2 (< 0.1) | 0.02 | 6 (0.1) | 0.04 |
Urinary tract carcinogenicityc (BIcMQ) | 9 (0.2) | 0.11 | 10 (0.2) | 0.12 | 13 (0.3) | 0.16 | 23 (0.2) | 0.14 |
Onset after 6 months’ treatment | 7 (0.2) | 0.12 | 8 (0.2) | 0.13 | 10 (0.3) | 0.16 | 18 (0.3) | 0.15 |
Liver injury (SMQ) | 157 (3.2) | 2.02 | 109 (2.2) | 1.36 | 135 (2.7) | 1.65 | 247 (2.4) | 1.51 |
Bone fractures (BIcMQ) | 134 (2.7) | 1.72 | 121 (2.5) | 1.52 | 107 (2.1) | 1.30 | 233 (2.3) | 1.42 |
Pancreatitis (SMQ) | 11 (0.2) | 0.14 | 8 (0.2) | 0.10 | 7 (0.1) | 0.08 | 15 (0.1) | 0.09 |
Amputation risk (ITT population) | 46 (0.9) | 0.52 | 46 (0.9) | 0.51 | 49 (1.0) | 0.54 | 95 (0.9) | 0.52 |
Minor | 27 (0.6) | 0.30 | 36 (0.7) | 0.40 | 40 (0.8) | 0.44 | 76 (0.8) | 0.41 |
Major | 19 (0.4) | 0.21 | 10 (0.2) | 0.11 | 9 (0.2) | 0.10 | 19 (0.2) | 0.10 |
Urinary Tract Infections
Placebo (n = 4904) | EMPA 10 mg (n = 4858) | EMPA 25 mg (n = 5057) | EMPA 10/25 mg (n = 10,177) | |||||
---|---|---|---|---|---|---|---|---|
n (%) | Rate/100 pt-yrs | n (%) | Rate/100 pt-yrs | n (%) | Rate/100 pt-yrs | n (%) | Rate/100 pt-yrs | |
UTIs (BIcMQ)a | ||||||||
Serious UTIs | 39 (0.8) | 0.49 | 27 (0.6) | 0.33 | 39 (0.8) | 0.47 | 66 (0.6) | 0.40 |
Requires or prolongs hospitalization | 38 (0.8) | 0.5 | 26 (0.5) | 0.3 | 39 (0.8) | 0.5 | 65 (0.6) | 0.4 |
Treatment discontinued | 15 (0.3) | 0.19 | 27 (0.6) | 0.33 | 25 (0.5) | 0.30 | 52 (0.5) | 0.31 |
History of chronic or recurrent UTIb | ||||||||
Yes | 100/277 (36.1) | 32.46 | 98/280 (35.0) | 28.58 | 102/313 (32.6) | 28.41 | 205/615 (33.5) | 28.82 |
No | 573/4267 (13.4) | 8.71 | 559/4221 (13.2) | 8.39 | 550/4402 (12.5) | 7.98 | 1126/8863 (12.7) | 8.20 |
Complicated UTIsc | 59 (1.2) | 0.75 | 39 (0.8) | 0.48 | 54 (1.1) | 0.65 | 93 (0.9) | 0.56 |
Genital infections (BIcMQ)d | ||||||||
Serious genital infections | 3 (0.1) | 0.04 | 8 (0.2) | 0.10 | 4 (0.1) | 0.05 | 12 (0.1) | 0.07 |
Requires or prolongs hospitalization | 3 (0.1) | < 0.1 | 8 (0.2) | 0.1 | 4 (0.1) | < 0.1 | 12 (0.1) | 0.1 |
Treatment discontinued | 2 (< 0.1) | 0.03 | 26 (0.5) | 0.32 | 21 (0.4) | 0.25 | 47 (0.5) | 0.28 |
History of chronic or recurrent genital infectione | ||||||||
Yes | 6/76 (7.9) | 5.25 | 17/76 (22.4) | 17.93 | 22/92 (23.9) | 23.47 | 39/172 (22.7) | 20.30 |
No | 66/4468 (1.5) | 0.88 | 243/4425 (5.5) | 3.27 | 249/4623 (5.4) | 3.25 | 498/9306 (5.4) | 3.25 |
Complicated genital infectionsf | 24 (0.5) | 0.30 | 29 (0.6) | 0.36 | 26 (0.5) | 0.31 | 55 (0.5) | 0.33 |
Genital Infections
Volume Depletion
Placebo (n = 4904) | EMPA 10 mg (n = 4858) | EMPA 25 mg (n = 5057) | EMPA 10/25 mg (n = 10,177) | |
---|---|---|---|---|
Volume depletiona (BIcMQ) | 147 (3.0) | 150 (3.1) | 169 (3.3) | 320 (3.1) |
Age (years) | ||||
< 65 | 62/3197 (1.9) | 59/3168 (1.9) | 73/3293 (2.2) | 132/6639 (2.0) |
65 to < 75 | 67/1377 (4.9) | 73/1390 (5.3) | 75/1426 (5.3) | 149/2887 (5.2) |
75 to < 85 | 16/318 (5.0) | 18/290 (6.2) | 19/327 (5.8) | 37/630 (5.9) |
≥ 85 | 2/12 (16.7) | 0/10 | 2/11 (18.2) | 2/21 (9.5) |
Hypotension at baseline | ||||
Yes | 17/244 (7.0) | 15/254 (5.9) | 9/276 (3.3) | 24/542 (4.4) |
No | 130/4602 (2.8) | 135/4548 (3.0) | 160/4727 (3.4) | 296/9525 (3.1) |
Use of diuretics at baseline | ||||
Yes | 83/1660 (5.0) | 79/1602 (4.9) | 96/1703 (5.6) | 175/3349 (5.2) |
No | 64/3244 (2.0) | 71/3256 (2.2) | 73/3354 (2.2) | 145/6828 (2.1) |
Use of loop diuretics at baseline | ||||
Yes | 36/488 (7.4) | 42/415 (10.1) | 47/489 (9.6) | 89/909 (9.8) |
No | 111/4416 (2.5) | 108/4443 (2.4) | 122/4568 (2.7) | 231/9268 (2.5) |
Use of ACE inhibitor/ARB at baseline | ||||
Yes | 121/3256 (3.7) | 126/3261 (3.9) | 142/3360 (4.2) | 269/6733 (4.0) |
No | 26/1648 (1.6) | 24/1597 (1.5) | 27/1697 (1.6) | 51/3444 (1.5) |
Use of antihypertensive drugs at baseline | ||||
Yes | 140/3922 (3.6) | 142/3857 (3.7) | 158/3986 (4.0) | 301/7996 (3.8) |
No | 7/982 (0.7) | 8/1001 (0.8) | 11/1071 (1.0) | 19/2181 (0.9) |
Diabetic Ketoacidosis
Urinary Tract Carcinogenicity
Liver Injury
Placebo (n = 4904) | EMPA 10 mg (n = 4858) | EMPA 25 mg (n = 5057) | EMPA 10/25 mg (n = 10,177) | |
---|---|---|---|---|
ALT and/or AST ≥ 3 × ULN | 65 (1.3) | 50 (1.0) | 45 (0.9) | 99 (1.0) |
ALT and/or AST ≥ 5 × ULN | 11 (0.2) | 18 (0.4) | 21 (0.4) | 40 (0.4) |
ALT and/or AST ≥ 3 × ULN with total bilirubin ≥ 2 × ULNb | 2 (< 0.1) | 5 (0.1) | 5 (0.1) | 10 (0.1) |
Bone Fractures
Pancreatitis
Lower Limb Amputation Risk
Renal Impairment
Placebo (n = 4904) | EMPA 10 mg (n = 4858) | EMPA 25 mg (n = 5057) | EMPA 10/25 mg (n = 10,177) | |||||
---|---|---|---|---|---|---|---|---|
n (%) | Rate/100 pt-yrs | n (%) | Rate/100 pt-yrs | n (%) | Rate/100 pt-yrs | n (%) | Rate/100 pt-yrs | |
Renal impairment | 169 (3.4) | 2.18 | 139 (2.9) | 1.75 | 152 (3.0) | 1.86 | 291 (2.9) | 1.78 |
Acute kidney injurya | 44 (0.9) | 0.56 | 29 (0.6) | 0.36 | 28 (0.6) | 0.34 | 57 (0.6) | 0.34 |
Renal impairment by baseline eGFR (CKD-EPI), ml/min/1.73 m2, n (%) | ||||||||
≥ 90 | 15/1933 (0.8) | 0.57 | 12/1998 (0.6) | 0.43 | 10/2041 (0.5) | 0.35 | 22/4177 (0.5) | 0.39 |
60 to < 90 | 63/2123 (3.0) | 1.73 | 57/2203 (2.6) | 1.48 | 60/2155 (2.8) | 1.56 | 117/4477 (2.6) | 1.50 |
45 to < 60 | 48/519 (9.2) | 4.92 | 46/464 (9.9) | 4.80 | 40/535 (7.5) | 4.09 | 86/1003 (8.6) | 4.44 |
30 to < 45 | 37/277 (13.4) | 7.85 | 21/182 (11.5) | 5.83 | 36/262 (13.7) | 8.38 | 57/445 (12.8) | 7.22 |
< 30 | 6/52 (11.5) | 13.87 | 3/10 (30.0) | 20.63 | 6/61 (9.8) | 8.77 | 9/71 (12.7) | 10.85 |