Introduction
Methods
Study Design and Patients
Treatment
Vital Signs and Laboratory Variables
Safety
Effectiveness
Liver Function
Statistical Analysis
Results
Patient Disposition
Patient Characteristics
Number of patients (%) or mean ± SD | ||
---|---|---|
Safety analysis set | Efficacy analysis set | |
Total | 11,051 (100.0) | 8788 (100.0) |
Sex | ||
Male | 6712 (60.7) | 5384 (61.3) |
Female | 4339 (39.3) | 3404 (38.7) |
Age, years | ||
n | 11,051 | 8788 |
56.9 ± 12.2 | 56.4 ± 12.0 | |
Body weight, kg | ||
n | 8170 | 6901 |
78.1 ± 17.3 | 78.5 ± 17.2 | |
BMI, kg/m2 | ||
n | 7489 | 6336 |
29.1 ± 5.3 | 29.2 ± 5.3 | |
Inpatient/outpatient | ||
Inpatient | 183 (1.7) | 153 (1.7) |
Outpatient | 10,868 (98.3) | 8635 (98.3) |
Duration of diabetes, years | ||
n | 7247 | 5942 |
8.0 ± 6.5 | 8.0 ± 6.4 | |
Duration of diabetes, category | ||
< 5 years | 2593 (23.5) | 2116 (24.1) |
≥ 5 years to < 10 years | 2171 (19.6) | 1775 (20.2) |
≥ 10 years to < 15 years | 1425 (12.9) | 1179 (13.4) |
≥ 15 years | 1058 (9.6) | 872 (9.9) |
Unknown | 3804 (34.4) | 2846 (32.4) |
Complications | ||
No | 1637 (14.8) | 1293 (14.7) |
Yes | 9321 (84.3) | 7443 (84.7) |
Unknown | 93 (0.8) | 52 (0.6) |
Type of complication (some patients had more than one complication) | ||
Diabetic neuropathy | 956 (8.7) | 787 (9.0) |
Diabetic nephropathy | 1819 (16.5) | 1516 (17.3) |
Diabetic retinopathy | 884 (8.0) | 741 (8.4) |
Cardiovascular and cerebrovascular disease | 1027 (9.3) | 748 (8.5) |
Myocardial infarction | 146 (1.3) | 118 (1.3) |
Angina pectoris | 467 (4.2) | 323 (3.7) |
Heart failure | 230 (2.1) | 161 (1.8) |
Arteriosclerosis obliterans | 139 (1.3) | 99 (1.1) |
Cerebrovascular disease | 261 (2.4) | 201 (2.3) |
Hypertension | 6183 (55.9) | 4921 (56.0) |
Dyslipidemia (hyperlipidemia) | 7055 (63.8) | 5657 (64.4) |
Osteoporosis | 184 (1.7) | 142 (1.6) |
Hyperuricemia | 1042 (9.4) | 812 (9.2) |
Urinary tract infection | 21 (0.2) | 18 (0.2) |
Genital infection | 8 (0.1) | 6 (0.1) |
Malignant tumor | 79 (0.7) | 62 (0.7) |
Other | 4050 (36.6) | 3264 (37.1) |
Hepatic function status* | ||
Normal | 8320 (75.3) | 6525 (74.2) |
Mild impairment | 2110 (19.1) | 1761 (20.0) |
Moderate impairment | 299 (2.7) | 252 (2.9) |
Severe impairment | 10 (0.1) | 9 (0.1) |
Unknown | 312 (2.8) | 241 (2.7) |
Renal function status* | ||
Normal | 9215 (83.4) | 7338 (83.7) |
Mild impairment | 1396 (12.6) | 1110 (12.6) |
Moderate impairment | 125 (1.1) | 98 (1.1) |
Severe impairment | 10 (0.1) | 7 (0.1) |
Unknown | 305 (2.8) | 235 (2.7) |
eGFR, mL/min/1.73 m2 | ||
n | 6757 | 5682 |
82.1 ± 21.7 | 82.4 ± 21.5 | |
eGFR, category, mL/min/1.73 m2 | ||
≥ 90 | 2162 (19.6) | 1841 (20.9) |
≥ 60 to < 90 | 3685 (33.3) | 3117 (35.5) |
≥ 45 to < 60 | 722 (6.5) | 582 (6.6) |
≥ 30 to < 45 | 155 (1.4) | 120 (1.4) |
< 30 | 33 (0.3) | 22 (0.3) |
Unknown | 4294 (38.9) | 3106 (35.3) |
Number of patients (%) or mean ± SD | ||
---|---|---|
Safety analysis set | Efficacy analysis set | |
Total | ||
– | 11,051 (100.0) | 8788 (100.0) |
Initial dose of ipragliflozin, mg | ||
25 | 1421 (12.9) | 0 |
50 | 9612 (87.0) | 8788 (100.0) |
75 | 0 | 0 |
100 | 14 (0.1) | 0 |
Other | 4 (0.0) | 0 |
Daily dose of ipragliflozin, mg | ||
n | 11,051 | 8788 |
47.5 ± 8.5 | 50.3 ± 2.8 | |
Concomitant treatment | ||
Concomitant antidiabetic drugs | ||
No | 1964 (17.8) | 1489 (16.9) |
Yes | 9006 (81.5) | 7248 (82.5) |
Unknown | 81 (0.7) | 51 (0.6) |
Number of concomitant antidiabetic drugs | ||
n | 11,051 | 8788 |
1.6 ± 1.2 | 1.6 ± 1.2 | |
Max | 6 | 6 |
Min | 0 | 0 |
0 | 2189 (19.8) | 1680 (19.1) |
1 | 3129 (28.3) | 2441 (27.8) |
2 | 3195 (28.9) | 2613 (29.7) |
3 | 1837 (16.6) | 1487 (16.9) |
≥ 4 | 619 (5.6) | 515 (5.9) |
Unknown | 82 (0.7) | 52 (0.6) |
Type of concomitant antidiabetic drugs (some patients had more than one concomitant drug) | ||
DPP-4 inhibitor | 6222 (56.3) | 5028 (57.2) |
Metformin | 4670 (42.3) | 3891 (44.3) |
Sulfonylurea | 3117 (28.2) | 2474 (28.2) |
Insulin injection | 1213 (11.0) | 1003 (11.4) |
α-Glucosidase inhibitor | 1150 (10.4) | 918 (10.4) |
Thiazolidinedione | 949 (8.6) | 774 (8.8) |
GLP-1 receptor agonist | 380 (3.4) | 333 (3.8) |
Fast-acting insulin secretagogue | 340 (3.1) | 279 (3.2) |
Others | 840 (7.6) | 657 (7.5) |
Concomitant diuretics | ||
No | 10,108 (91.5) | 8065 (91.8) |
Yes | 839 (7.6) | 643 (7.3) |
Unknown | 104 (0.9) | 80 (0.9) |
Type of concomitant diuretics (some patients had more than one concomitant drug) | ||
Thiazide diuretic | 215 (1.9) | 168 (1.9) |
Loop diuretic | 204 (1.8) | 151 (1.7) |
Potassium-sparing diuretic | 172 (1.6) | 133 (1.5) |
Vasopressin antagonist | 6 (0.1) | 5 (0.1) |
Osmotic diuretic | 1 (0.0) | 0 |
Carbonate dehydratase inhibitor | 0 | 0 |
Others | 365 (3.3) | 287 (3.3) |
Other concomitant drugs | ||
No | 3051 (27.6) | 2436 (27.7) |
Yes | 7876 (71.3) | 6275 (71.4) |
Unknown | 124 (1.1) | 77 (0.9) |
Type of other concomitant drugs (some patients had more than one concomitant drug) | ||
Antihypertensive drug | 4934 (44.6) | 3923 (44.6) |
ARB | 2519 (22.8) | 2019 (23.0) |
CCB | 2306 (20.9) | 1790 (20.4) |
ARB + CCB | 1373 (12.4) | 1107 (12.6) |
Statin | 4151 (37.6) | 3280 (37.3) |
Antiplatelet drug | 974 (8.8) | 737 (8.4) |
Antipeptic ulcer drug | 989 (8.9) | 790 (9.0) |
Antihyperuricemic drug | 726 (6.6) | 564 (6.4) |
Others | 3801 (34.4) | 3002 (34.2) |
Vital Signs
Parameters | Actual value | Change from baseline | ||||
---|---|---|---|---|---|---|
Baseline | 12 months | 1 month | 3 months | 6 months | 12 months | |
SBP (mmHg) | 133.3 ± 15.1 (n = 7161) | 129.3 ± 13.5 (n = 5418) | − 3.8 ± 13.3* (n = 5185) | − 3.8 ± 14.0* (n = 6303) | − 3.4 ± 14.6* (n = 5315) | − 4.3 ± 14.6* (n = 4973) |
DBP (mmHg) | 78.4 ± 11.0 (n = 7159) | 75.9 ± 10.2 (n = 5414) | − 1.9 ± 9.4* (n = 5184) | − 2.0 ± 9.7* (n = 6300) | − 1.7 ± 10.1* (n = 5309) | − 2.6 ± 10.0* (n = 4968) |
Heart rate (beats/min)a | 77.9 ± 12.3 (n = 5191) | 76.5 ± 11.6 (n = 4040) | − 0.6 ± 8.7* (n = 3481) | − 0.8 ± 9.1* (n = 4270) | − 0.9 ± 9.4* (n = 3593) | − 0.9 ± 9.4* (n = 3325) |
AST (GOT) (U/L) | 30.2 ± 19.4 (n = 5823) | 25.5 ± 14.3 (n = 4381) | − 1.9 ± 12.1* (n = 3253) | − 3.4 ± 14.0* (n = 4652) | − 4.5 ± 15.1* (n = 3998) | − 4.6 ± 16.3* (n = 3799) |
ALT (GPT) (U/L) | 38.2 ± 29.1 (n = 5892) | 30.3 ± 22.8 (n = 4439) | − 3.2 ± 14.7* (n = 3280) | − 5.8 ± 18.7* (n = 4735) | − 7.4 ± 20.2* (n = 4053) | − 7.9 ± 21.1* (n = 3868) |
γ-GTP (U/L) | 58.7 ± 70.8 (n = 5433) | 47.2 ± 65.8 (n = 4082) | − 7.9 ± 29.9* (n = 2990) | − 9.2 ± 40.0* (n = 4308) | − 10.6 ± 40.6* (n = 3655) | − 10.9 ± 42.2* (n = 3493) |
Total cholesterol (mg/dL) | 196.8 ± 40.0 (n = 3732) | 192.5 ± 34.8 (n = 2750) | − 4.8 ± 28.8* (n = 2018) | − 1.9 ± 28.6* (n = 2941) | − 0.8 ± 30.9 (n = 2457) | − 2.5 ± 30.7* (n = 2309) |
LDL-C (mg/dL) | 114.6 ± 31.9 (n = 5349) | 110.1 ± 28.5 (n = 4073) | − 3.3 ± 23.1* (n = 2937) | − 1.7 ± 24.5* (n = 4238) | − 2.4 ± 26.0* (n = 3631) | − 4.0 ± 26.7* (n = 3436) |
HDL-C (mg/dL) | 50.8 ± 13.6 (n = 5592) | 53.9 ± 14.7 (n = 4239) | 0.3 ± 7.0* (n = 3152) | 1.4 ± 8.3* (n = 4498) | 3.1 ± 8.8* (n = 3867) | 2.9 ± 9.2* (n = 3660) |
Triglyceride (mg/dL) | 197.0 ± 184.3 (n = 5861) | 175.5 ± 164.9 (n = 4411) | − 18.1 ± 156.2* (n = 3321) | − 16.6 ± 156.2* (n = 4722) | − 18.9 ± 143.1* (n = 4070) | − 16.3 ± 143.2* (n = 3847) |
Uric acid (mg/dL) | 5.3 ± 1.3 (n = 5191) | 5.0 ± 1.2 (n = 3905) | − 0.35 ± 0.91* (n = 2809) | − 0.29 ± 0.90* (n = 4077) | − 0.32 ± 0.93* (n = 3461) | − 0.29 ± 0.95* (n = 3297) |
Hematocrit (%)a | 43.1 ± 4.3 (n = 6078) | 45.1 ± 4.3 (n = 4711) | 1.0 ± 2.2* (n = 3176) | 1.6 ± 2.6* (n = 4609) | 1.9 ± 2.7* (n = 3907) | 1.9 ± 2.8* (n = 3753) |
BUN (mg/dL)a | 14.8 ± 4.5 (n = 5853) | 16.0 ± 4.4 (n = 4497) | 0.7 ± 3.5* (n = 3125) | 0.8 ± 3.6* (n = 4491) | 1.0 ± 3.7* (n = 3781) | 1.2 ± 3.7* (n = 3645) |
Serum Cr (mg/dL)a | 0.74 ± 0.22 (n = 6757) | 0.75 ± 0.23 (n = 5232) | 0.03 ± 0.09* (n = 3620) | 0.02 ± 0.09* (n = 5300) | 0.02 ± 0.10* (n = 4462) | 0.02 ± 0.10* (n = 4292) |
Laboratory Variables
Safety
STELLA-LONG TERM | Pre-approval clinical trials | |
---|---|---|
Number of patients | 11,051 | 1669 |
Number of patients with ADRs | 1616 | 549 |
Number of ADRs | 2239 | 887 |
Incidence rate ADRs | 14.6% | 32.9% |
System organ class | ||
Infections and infestations | 201 (1.8) | 64 (3.8) |
Neoplasms benign, malignant, and unspecified (incl. cysts and polyps) | 25 (0.23) | 4 (0.24) |
Blood and lymphatic system disorders | 9 (0.08) | 8 (0.48) |
Immune system disorders | 1 (0.01) | 0 |
Endocrine disorders | 1 (0.01) | 0 |
Metabolism and nutrition disorders | 161 (1.5) | 20 (1.2) |
Psychiatric disorders | 9 (0.08) | 3 (0.18) |
Nervous system disorders | 74 (0.67) | 42 (2.5) |
Eye disorders | 8 (0.07) | 17 (1.0) |
Ear and labyrinth disorders | 1 (0.01) | 5 (0.30) |
Cardiac disorders | 31 (0.28) | 10 (0.60) |
Vascular disorders | 34 (0.31) | 7 (0.42) |
Respiratory, thoracic, and mediastinal disorders | 11 (0.10) | 7 (0.42) |
Gastrointestinal disorders | 100 (0.90) | 101 (6.1) |
Hepatobiliary disorders | 70 (0.63) | 8 (0.48) |
Skin and subcutaneous tissue disorders | 147 (1.3) | 48 (2.9) |
Musculoskeletal and connective tissue disorders | 23 (0.21) | 13 (0.78) |
Renal and urinary disorders | 644 (5.8) | 176 (10.6) |
Reproductive system and breast disorders | 88 (0.80) | 25 (1.5) |
General disorders and administration site conditions | 72 (0.65) | 101 (6.1) |
Investigations | 205 (1.9) | 133 (8.0) |
Injury, poisoning, and procedural complications | 10 (0.09) | 0 |
STELLA-LONG TERM | Pre-approval clinical trials | |
---|---|---|
Number of patients with serious ADRs | 107 | 14 |
Number of serious ADRs | 121 | 15 |
Incidence rate of serious ADRs | 0.97% | 0.84% |
System organ class MedDRA preferred term | ||
Infections and infestations | 9 (0.08) | 2 (0.12) |
Escherichia sepsis | 1 (0.01) | 0 |
Liver abscess | 1 (0.01) | 0 |
Peritonsillar abscess | 1 (0.01) | 0 |
Pneumonia | 1 (0.01) | 0 |
Pyelonephritis | 0 | 2 (0.12) |
Pyelonephritis acute | 2 (0.02) | 0 |
Urinary tract infection | 3 (0.03) | 0 |
Genital herpes simplex | 1 (0.01) | 0 |
Neoplasms benign, malignant, and unspecified (incl. cysts and polyps) | 20 (0.18) | 3 (0.18) |
Colon cancer | 5 (0.05) | 1 (0.06) |
Metastases to lymph nodes | 1 (0.01) | 0 |
Pancreatic carcinoma | 6 (0.05) | 0 |
Pancreatic carcinoma metastatic | 1 (0.01) | 0 |
Squamous cell carcinoma of skin | 1 (0.01) | 0 |
Uterine cancer | 0 | 1 (0.06) |
Breast cancer female | 2 (0.02) | 0 |
Lung neoplasm malignant | 1 (0.01) | 0 |
Prostate cancer | 1 (0.01) | 1 (0.06) |
Lung neoplasm | 1 (0.01) | 0 |
Thyroid cancer | 1 (0.01) | 0 |
Intraductal proliferative breast lesion | 1 (0.01) | 0 |
Blood and lymphatic system disorders | 0 | 1 (0.06) |
Hemolytic anemia | 0 | 1 (0.06) |
Endocrine disorders | 1 (0.01) | 0 |
Hypothyroidism | 1 (0.01) | 0 |
Metabolism and nutrition disorders | 6 (0.05) | 0 |
Dehydration | 2 (0.02) | 0 |
Hyperglycemia | 1 (0.01) | 0 |
Hyperphagia | 1 (0.01) | 0 |
Hypoglycemia | 2 (0.02) | 0 |
Psychiatric disorders | 2 (0.02) | 0 |
Depression | 2 (0.02) | 0 |
Nervous system disorders | 21 (0.19) | 1 (0.06) |
Cerebral hemorrhage | 2 (0.02) | 0 |
Cerebral infarction | 11 (0.10) | 1 (0.06) |
Depressed level of consciousness | 1 (0.01) | 0 |
Dizziness | 1 (0.01) | 0 |
Somnolence | 1 (0.01) | 0 |
Transient ischemic attack | 1 (0.01) | 0 |
Lacunar infarction | 3 (0.03) | 0 |
Putamen hemorrhage | 1 (0.01) | 0 |
Eye disorders | 3 (0.03) | 0 |
Diabetic retinopathy | 1 (0.01) | 0 |
Retinal hemorrhage | 2 (0.02) | 0 |
Ear and labyrinth disorders | 1 (0.01) | 0 |
Sudden hearing loss | 1 (0.01) | 0 |
Cardiac disorders | 19 (0.17) | 2 (0.12) |
Acute myocardial infarction | 5 (0.05) | 1 (0.06) |
Angina pectoris | 2 (0.02) | 0 |
Angina unstable | 3 (0.03) | 1 (0.06) |
Atrial fibrillation | 1 (0.01) | 0 |
Cardiac failure congestive | 2 (0.02) | 0 |
Cardiovascular disorder | 1 (0.01) | 0 |
Coronary artery disease | 1 (0.01) | 0 |
Myocardial infarction | 5 (0.05) | 0 |
Vascular disorders | 3 (0.03) | 0 |
Hypertension | 2 (0.02) | 0 |
Varicose vein | 1 (0.01) | 0 |
Gastrointestinal disorders | 3 (0.03) | 1 (0.06) |
Duodenal ulcer | 1 (0.01) | 0 |
Gastric ulcer hemorrhage | 1 (0.01) | 0 |
Gastroesophageal reflux disease | 1 (0.01) | 0 |
Pancreatitis acute | 1 (0.01) | 0 |
Upper gastrointestinal hemorrhage | 0 | 1 (0.06) |
Hepatobiliary disorders | 7 (0.06) | 0 |
Cholecystitis | 2 (0.02) | 0 |
Cholecystitis acute | 1 (0.01) | 0 |
Cholelithiasis | 1 (0.01) | 0 |
Hepatic cirrhosis | 2 (0.02) | 0 |
Jaundice cholestatic | 1 (0.01) | 0 |
Liver disorder | 1 (0.01) | 0 |
Skin and subcutaneous tissue disorders | 4 (0.04) | 0 |
Drug eruption | 1 (0.01) | 0 |
Eczema | 1 (0.01) | 0 |
Skin ulcer | 1 (0.01) | 0 |
Urticaria | 1 (0.01) | 0 |
Renal and urinary disorders | 6 (0.05) | 3 (0.18) |
Hematuria | 1 (0.01) | 0 |
Nephrolithiasis | 0 | 1 (0.06) |
Neurogenic bladder | 1 (0.01) | 0 |
Renal disorder | 2 (0.02) | 1 (0.06) |
Renal vessel disorder | 1 (0.01) | 0 |
Ureterolithiasis | 1 (0.01) | 1 (0.06) |
Reproductive system and breast disorders | 1 (0.01) | 0 |
Prostatitis | 1 (0.01) | 0 |
General disorders and administration site conditions | 1 (0.01) | 2 (0.12) |
Death | 0 | 1 (0.06) |
Pain | 0 | 1 (0.06) |
Thirst | 1 (0.01) | 0 |
Investigations | 1 (0.01) | 0 |
Gamma-glutamyl transferase increased | 1 (0.01) | 0 |
Injury, poisoning, and procedural complications | 4 (0.04) | 0 |
Fall | 1 (0.01) | 0 |
Femoral neck fracture | 1 (0.01) | 0 |
Foot fracture | 1 (0.01) | 0 |
Ligament sprain | 1 (0.01) | 0 |
Road traffic accident | 1 (0.01) | 0 |
Subarachnoid hemorrhage | 1 (0.01) | 0 |
Contusion | 1 (0.01) | 0 |
Brain contusion | 1 (0.01) | 0 |
STELLA-LONG TERM (safety analysis set n = 11,051) | Pre-approval clinical trials | ||||||
---|---|---|---|---|---|---|---|
Total number of patients experiencing an ADR | Serious | Non-serious | Total (n = 1669) | ||||
All ADRs | 1616 | (14.6) | 107 | (0.97) | 1539 | (13.9) | (32.9) |
ADRs of special interest | |||||||
Polyuria/pollakiuria | 571 | (5.2) | 1 | (0.01) | 570 | (5.2) | (10.0) |
Volume depletion-related events, including dehydration | 196 | (1.8) | 9 | (0.08) | 189 | (1.7) | (4.5) |
Skin complications | 166 | (1.5) | 4 | (0.04) | 162 | (1.5) | (4.0) |
Genital infection | 135 | (1.2) | 2 | (0.02) | 133 | (1.2) | (2.0) |
Urinary tract infection | 115 | (1.0) | 5 | (0.05) | 110 | (1.0) | (1.8) |
Renal disorder | 115 | (1.0) | 3 | (0.03) | 112 | (1.0) | (4.8) |
Hepatic disorder | 82 | (0.74) | 6 | (0.05) | 78 | (0.71) | (1.0) |
Hypoglycemia | 39 | (0.35) | 3 | (0.03) | 36 | (0.33) | (1.4) |
Cardiovascular diseasea | 30 | (0.27) | 19 | (0.17) | 11 | (0.10) | (1.0) |
Cerebrovascular diseaseb | 23 | (0.21) | 20 | (0.18) | 3 | (0.03) | (0.2) |
Malignant tumor | 22 | (0.20) | 19 | (0.17) | 3 | (0.03) | (0.2) |
Ketoacidosis, events related to ketone-body increase | 3 | (0.03) | 0 | (0.00) | 3 | (0.03) | (1.0) |
Fracture | 2 | (0.02) | 1 | (0.01) | 1 | (0.01) | 0 |
< 7 days | 7–< 15 days | 15–< 30 days | 30–< 45 days | 45–< 60 days | 60–< 90 days | 90–< 180 days | 180–< 270 days | 270–< 360 days | 360–< 720 days | Unknown | |
---|---|---|---|---|---|---|---|---|---|---|---|
All ADRs (2239 events) | 448 (20.0) | 212 (9.5) | 315 (14.1) | 195 (8.7) | 101 (4.5) | 176 (7.9) | 317 (14.2) | 201 (8.0) | 185 (7.4) | 72 (3.5) | 30 (1.3) |
ADRs of special interest | |||||||||||
Hypoglycemia (42 events) | 7 (16.7) | 6 (14.3) | 3 (7.1) | 1 (2.4) | 3 (7.1) | 7 (16.7) | 3 (7.1) | 4 (9.5) | 5 (11.9) | 3 (7.1) | 0 |
Genital infection (140 events) | 14 (10.0) | 15 (10.7) | 21 (15.0) | 10 (7.1) | 9 (6.4) | 17 (12.1) | 23 (16.4) | 17 (12.1) | 11 (7.9) | 3 (2.1) | 0 |
Urinary tract infection (117 events) | 3 (2.6) | 9 (7.7) | 23 (19.7) | 4 (3.4) | 7 (6.0) | 16 (13.7) | 30 (25.6) | 15 (12.8) | 9 (7.7) | 1 (0.9) | 0 |
Polyuria/pollakiuria (784 events) | 320 (40.8) | 97 (12.4) | 142 (18.1) | 86 (11.0) | 31 (4.0) | 25 (3.2) | 46 (5.9) | 17 (2.2) | 10 (1.3) | 4 (0.5) | 6 (0.8) |
Volume depletion (238 events) | 33 (13.9) | 7 (2.9) | 40 (16.8) | 30 (12.6) | 8 (3.4) | 27 (11.3) | 42 (17.6) | 19 (8.0) | 12 (5.0) | 11 (4.6) | 9 (3.8) |
Renal disorder (123 events) | 1 (0.8) | 5 (4.1) | 17 (13.8) | 11 (8.9) | 7 (5.7) | 16 (13.0) | 27 (22.0) | 16 (13.0) | 10 (8.1) | 12 (9.8) | 1 (0.8) |
Hepatic disorder (87 events) | 1 (1.1) | 1 (1.1) | 12 (13.8) | 10 (11.5) | 6 (6.9) | 9 (10.3) | 22 (25.3) | 10 (11.5) | 7 (8.0) | 8 (9.2) | 1 (1.1) |
Fracture (3 events) | 0 | 0 | 0 | 0 | 0 | 1 (33.3) | 0 | 1 (33.3) | 1 (33.3) | 0 | 0 |
Malignant tumor (23 events) | 0 | 0 | 0 | 0 | 0 | 1 (4.3) | 5 (21.7) | 7 (30.4) | 3 (13.0) | 2 (8.7) | 5 (21.7) |
Cardiovascular disease (32 events) | 1 (3.1) | 0 | 3 (9.4) | 1 (3.1) | 4 (12.5) | 2 (6.3) | 4 (12.5) | 5 (15.6) | 8 (25.0) | 4 (12.5) | 0 |
Cerebrovascular disease (23 events) | 0 | 2 (8.7) | 0 | 1 (4.3) | 1 (4.3) | 3 (13.0) | 5 (21.7) | 4 (17.4) | 5 (21.7) | 2 (8.7) | 0 |
Skin complications (170 events) | 48 (28.2) | 31 (18.2) | 18 (10.6) | 5 (2.9) | 9 (5.3) | 16 (9.4) | 22 (12.9) | 11 (6.5) | 7 (4.1) | 1 (0.6) | 2 (1.2) |
Ketone body-related events (3 events) | 0 | 0 | 1 (33.3) | 0 | 0 | 0 | 0 | 1 (33.3) | 1 (33.3) | 0 | 0 |
Total number of patients experiencing an ADR | Ipragliflozin treatment status | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Continued | Dose reduction | Interruption or discontinuation due to the event | Interruption or discontinuation for other reasons | Completion of treatment before ADR | Unknown | ||||||||
All ADRs | 1616 | 986 | (61.0) | 20 | (1.2) | 622 | (38.5) | 57 | (3.5) | 7 | (0.4) | 7 | (0.4) |
ADRs of special interest | |||||||||||||
Skin complications | 166 | 30 | (18.1) | 1 | (0.6) | 135 | (81.3) | 0 | (0.0) | 0 | (0.0) | 0 | (0.0) |
Ketoacidosis, events related to ketone-body increase | 3 | 1 | (33.3) | 0 | (0.0) | 2 | (66.7) | 0 | (0.0) | 0 | (0.0) | 0 | (0.0) |
Genital infection | 135 | 58 | (43.0) | 1 | (0.7) | 77 | (57.0) | 0 | (0.0) | 1 | (0.7) | 0 | (0.0) |
Fracture | 2 | 2 | (100.0) | 0 | (0.0) | 1 | (50.0) | 0 | (0.0) | 0 | (0.0) | 0 | (0.0) |
Hypoglycemia | 39 | 20 | (51.3) | 2 | (5.1) | 18 | (46.2) | 1 | (2.6) | 0 | (0.0) | 0 | (0.0) |
Urinary tract infection | 115 | 64 | (55.7) | 0 | (0.0) | 53 | (46.1) | 1 | (0.9) | 0 | (0.0) | 0 | (0.0) |
Cerebrovascular disease | 23 | 8 | (34.8) | 1 | (4.4) | 10 | (43.5) | 2 | (8.7) | 0 | (0.0) | 2 | (8.7) |
Cardiovascular disease | 30 | 16 | (53.3) | 0 | (0.0) | 13 | (43.3) | 0 | (0.0) | 0 | (0.0) | 1 | (3.3) |
Volume depletion-related events, including dehydration | 196 | 121 | (61.7) | 2 | (1.0) | 72 | (36.7) | 7 | (3.6) | 0 | (0.0) | 0 | (0.0) |
Polyuria/pollakiuria | 571 | 413 | (72.3) | 10 | (1.8) | 132 | (23.1) | 19 | (3.3) | 0 | (0.0) | 0 | (0.0) |
Malignant tumor | 22 | 14 | (63.6) | 0 | (0.0) | 4 | (18.2) | 1 | (4.5) | 1 | (4.5) | 2 | (9.1) |
Renal disorder | 115 | 92 | (80.0) | 0 | (0.0) | 17 | (14.8) | 6 | (5.2) | 0 | (0.0) | 1 | (0.9) |
Hepatic disorder | 82 | 65 | (79.3) | 0 | (0.0) | 11 | (13.4) | 5 | (6.1) | 2 | (2.4) | 1 | (1.2) |
Total | Outcome | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Resolved | Remission | Not recovered | Sequelae | Death | Unknown | ||||||||
All ADRs | 2239 | 1206 | (53.9) | 707 | (31.6) | 202 | (9.0) | 8 | (0.4) | 9 | (0.4) | 107 | (4.8) |
ADRs of special interest | |||||||||||||
Hypoglycemia | 42 | 38 | (90.5) | 4 | (9.5) | 0 | 0 | 0 | 0 | ||||
Genital infection | 140 | 98 | (70.0) | 33 | (23.6) | 6 | (4.3) | 0 | 0 | 3 | (2.1) | ||
Urinary tract infection | 117 | 96 | (82.1) | 19 | (16.2) | 1 | (0.9) | 0 | 0 | 1 | (0.9) | ||
Polyuria/pollakiuria | 784 | 313 | (39.9) | 353 | (45.0) | 88 | (11.2) | 0 | 0 | 30 | (3.8) | ||
Volume depletion | 238 | 152 | (63.9) | 70 | (29.4) | 10 | (4.2) | 1 | (0.4) | 0 | 5 | (2.1) | |
Renal disorder | 123 | 59 | (48.0) | 31 | (25.2) | 17 | (13.8) | 0 | 0 | 16 | (13.0) | ||
Hepatic disorder | 87 | 43 | (49.4) | 12 | (13.8) | 16 | (18.4) | 0 | 1 | (1.1) | 15 | (17.2) | |
Fracture | 3 | 1 | (33.3) | 2 | (66.7) | 0 | 0 | 0 | 0 | ||||
Malignant tumor | 23 | 4 | (17.4) | 6 | (26.1) | 3 | (13.0) | 0 | 5 | (21.7) | 5 | (21.7) | |
Cardiovascular disease | 32 | 15 | (46.9) | 11 | (34.4) | 3 | (9.4) | 0 | 2 | (6.3) | 1 | (3.1) | |
Cerebrovascular disease | 23 | 8 | (34.8) | 6 | (26.1) | 0 | 8 | (34.8) | 0 | 1 | (4.3) | ||
Skin complications | 170 | 121 | (71.2) | 42 | (24.7) | 7 | (4.1) | 0 | 0 | 0 | |||
Ketone body-related events | 3 | 2 | (66.7) | 1 | (33.3) | 0 | 0 | 0 | 0 |
Effectiveness
Liver Function
n | Pearson correlation coefficient | P value | |
---|---|---|---|
Changes in HbA1c | 2145 | 0.149 | < 0.001 |
Changes in fasting plasma glucose | 1198 | 0.106 | < 0.001 |
Changes in fasting insulin | 103 | 0.103 | 0.302 |
Changes in body weight | 1837 | 0.206 | < 0.001 |
Changes in waist circumference | 351 | 0.006 | 0.918 |
Changes in systolic blood pressure | 1886 | 0.032 | 0.171 |
Changes in diastolic blood pressure | 1884 | 0.081 | < 0.001 |
Changes in total bilirubin | 904 | 0.102 | 0.002 |
Changes in triglycerides | 2018 | 0.050 | 0.023 |