Table 2.
Treatment-emergent AEs
| Dose | Total | SBP | DBP | LDL-C | |||||
|---|---|---|---|---|---|---|---|---|---|
| <130 mmHg | ≥130 mmHg | <80 mmHg | ≥80 mmHg | <120 mg/dL | ≥120 mg/dL | ||||
| 100 mg | Numbers of patients | 584 | 295 | 289 | 334 | 250 | 296 | 288 | |
| Patients with ≥1 AE | 478 (81.8) | 246 (83.4) | 232 (80.3) | 274 (82.0) | 204 (81.6) | 244 (82.4) | 234 (81.3) | ||
| Patients with ≥1 SAE | 30 (5.1) | 14 (4.7) | 16 (5.5) | 20 (6.0) | 10 (4.0) | 18 (6.1) | 12 (4.2) | ||
| Withdrawals because of an AE | 20 (3.4) | 11 (3.7) | 9 (3.1) | 13 (3.9) | 7 (2.8) | 12 (4.1) | 8 (2.8) | ||
| Death | 2 (0.3) | 1 (0.3) | 1 (0.3) | 1 (0.3) | 1 (0.4) | 0 (0.0) | 2 (0.7) | ||
| Hypoglycemia | |||||||||
| Hypoglycemia* | 44 (7.5) | 18 (6.1) | 26 (9.0) | 24 (7.2) | 20 (8.0) | 28 (9.5) | 16 (5.6) | ||
| Asymptomatic hypoglycemia* | 54 (9.2) | 30 (10.2) | 24 (8.3) | 36 (10.8) | 18 (7.2) | 31 (10.5) | 23 (8.0) | ||
| Serious hypoglycemia* | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
| Genital infection (male)†‡ | 3 (0.7) | 1 (0.5) | 2 (0.9) | 2 (0.9) | 1 (0.5) | 2 (0.9) | 1 (0.5) | ||
| Genital infection (female)†¶ | 14 (8.6) | 9 (10.1) | 5 (6.8) | 10 (8.8) | 4 (8.2) | 8 (10.3) | 6 (7.1) | ||
| Urinary tract infection# | 19 (3.3) | 8 (2.7) | 11 (3.8) | 12 (3.6) | 7 (2.8) | 8 (2.7) | 11 (3.8) | ||
| Volume depletion§ | 7 (1.2) | 4 (1.4) | 3 (1.0) | 4 (1.2) | 3 (1.2) | 4 (1.4) | 3 (1.0) | ||
| Osmotic diuresis** | 35 (6.0) | 19 (6.4) | 16 (5.5) | 19 (5.7) | 16 (6.4) | 21 (7.1) | 14 (4.9) | ||
| Skin and subcutaneous tissue disorders†† | 76 (13.0) | 44 (14.9) | 32 (11.1) | 54 (16.2) | 22 (8.8) | 40 (13.5) | 36 (12.5) | ||
| CV events‡‡ | 7 (1.2) | 4 (1.4) | 3 (1.0) | 5 (1.5) | 2 (0.8) | 3 (1.0) | 4 (1.4) | ||
| 200 mg | Numbers of patients | 715 | 378 | 337 | 395 | 320 | 345 | 370 | |
| Patients with ≥1 AE | 592 (82.8) | 316 (83.6) | 276 (81.9) | 333 (84.3) | 259 (80.9) | 279 (80.9) | 313 (84.6) | ||
| Patients with ≥1 SAE | 32 (4.5) | 9 (2.4) | 23 (6.8) | 15 (3.8) | 17 (5.3) | 13 (3.8) | 19 (5.1) | ||
| Withdrawals because of an AE | 30 (4.2) | 12 (3.2) | 18 (5.3) | 18 (4.6) | 12 (3.8) | 12 (3.5) | 18 (4.9) | ||
| Death | 3 (0.4) | 0 (0.0) | 3 (0.9) | 1 (0.3) | 2 (0.6) | 2 (0.6) | 1 (0.3) | ||
| Hypoglycemia | |||||||||
| Hypoglycemia* | 44 (6.2) | 23 (6.1) | 21 (6.2) | 23 (5.8) | 21 (6.6) | 19 (5.5) | 25 (6.8) | ||
| Asymptomatic hypoglycemia* | 63 (8.8) | 32 (8.5) | 31 (9.2) | 43 (10.9) | 20 (6.3) | 29 (8.4) | 34 (9.2) | ||
| Serious hypoglycemia* | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | ||
| Genital infection (male)†‡ | 3 (0.6) | 3 (1.1) | 0 (0.0) | 2 (0.8) | 1 (0.4) | 3 (1.2) | 0 (0.0) | ||
| Genital infection (female)†¶ | 25 (11.8) | 14 (12.2) | 11 (11.3) | 15 (10.2) | 10 (15.4) | 6 (7.0) | 19 (15.1) | ||
| Urinary tract infection# | 16 (2.2) | 15 (4.0) | 1 (0.3) | 14 (3.5) | 2 (0.6) | 8 (2.3) | 8 (2.2) | ||
| Volume depletion§ | 15 (2.1) | 11 (2.9) | 4 (1.2) | 11 (2.8) | 4 (1.3) | 12 (3.5) | 3 (0.8) | ||
| Osmotic diuresis** | 44 (6.2) | 29 (7.7) | 15 (4.5) | 22 (5.6) | 22 (6.9) | 24 (7.0) | 20 (5.4) | ||
| Skin and subcutaneous tissue disorders†† | 87 (12.2) | 45 (11.9) | 42 (12.5) | 49 (12.4) | 38 (11.9) | 33 (9.6) | 54 (14.6) | ||
| CV events‡‡ | 13 (1.8) | 8 (2.1) | 5 (1.5) | 8 (2.0) | 5 (1.6) | 6 (1.7) | 7 (1.9) | ||
Data are presented as the n (%) of patients
AE adverse event, CV cardiovascular, DBP diastolic blood pressure, LDL-C low-density lipoprotein cholesterol, SAE serious adverse event, SBP systolic blood pressure
* Events that occurred during the follow-up period were not included. Hypoglycemia was defined as the presence of typical hypoglycemia symptoms irrespective of the blood glucose. Asymptomatic hypoglycemia was defined as a blood glucose of ≤70 mg/dL in the absence of typical hypoglycemic symptoms
†Percentages are calculated for male and female separately
‡Includes balanoposthitis, posthitis, and balanitis
¶Includes vulvovaginal candidiasis, vulvovaginitis, genital infection fungal, vaginal infection, genital candidiasis, and vulvitis
#Includes cystitis, urinary tract infection, and pyelonephritis
§Includes postural dizziness, syncope, dehydration, orthostatic hypotension, hypotension, and blood pressure decreased
** Includes micturition urgency, nocturia, pollakiuria, polyuria, urine output increased, dry mouth, polydipsia, and thirst
††Includes diabetic ulcer, rash and urticaria
‡‡Includes increased creatine phosphokinase, lacunar infarction, stroke, carotid arterial stenosis, acute myocardial infarction, and myocardial infarction