TABLE 3.
On‐treatment adverse events (AEs) (A) and most frequent gastrointestinal AEs (B) in Japanese patients in PIONEER 1, 3, 4 and 8
| (A) | Treatment group | Patients, N | Any AE, n (%) | Serious AE, n (%) | Severity, n (%) | AE leading to trial product discontinuation, n (%) | Severe or BG‐confirmed a symptomatic hypoglycaemia, n (%) | ||
|---|---|---|---|---|---|---|---|---|---|
| Trial (background regimen) | Mild | Moderate | Severe | ||||||
| PIONEER 1 (diet and exercise) | Oral semaglutide 3 mg | 29 | 15 (51.7) | 0 | 15 (51.7) | 1 (3.4) | 0 | 0 | 0 |
| Oral semaglutide 7 mg | 29 | 16 (55.2) | 0 | 15 (51.7) | 2 (6.9) | 0 | 1 (3.4) | 0 | |
| Oral semaglutide 14 mg | 28 | 18 (64.3) | 0 | 17 (60.7) | 3 (10.7) | 0 | 2 (7.1) | 0 | |
| Placebo | 30 | 12 (40.0) | 1 (3.3) | 10 (33.3) | 3 (10.0) | 0 | 1 (3.3) | 0 | |
| PIONEER 3 (metformin ± SU) | Oral semaglutide 3 mg | 52 | 39 (75.0) | 4 (7.7) | 36 (69.2) | 9 (17.3) | 1 (1.9) | 2 (3.8) | 0 |
| Oral semaglutide 7 mg | 52 | 46 (88.5) | 7 (13.5) | 42 (80.8) | 11 (21.2) | 3 (5.8) | 5 (9.6) | 1 (1.9) | |
| Oral semaglutide 14 mg | 51 | 43 (84.3) | 6 (11.8) | 42 (82.4) | 10 (19.6) | 3 (5.9) | 8 (15.7) | 2 (3.9) | |
| Sitagliptin 100 mg | 52 | 47 (90.4) | 2 (3.8) | 45 (86.5) | 7 (13.5) | 2 (3.8) | 1 (1.9) | 2 (3.8) | |
| PIONEER 4 (metformin ± SGLT2i) | Oral semaglutide 14 mg | 31 | 28 (90.3) | 1 (3.2) | 28 (90.3) | 3 (9.7) | 1 (3.2) | 1 (3.2) | 1 (3.2) |
| Liraglutide 1.8 mg | 29 | 26 (89.7) | 1 (3.4) | 26 (89.7) | 0 | 1 (3.4) | 1 (3.4) | 1 (3.4) | |
| Placebo | 15 | 10 (66.7) | 0 | 10 (66.7) | 1 (6.7) | 0 | 0 | 0 | |
| PIONEER 8 (insulin ± metformin) | Oral semaglutide 3 mg | 49 | 39 (79.6) | 7 (14.3) | 39 (79.6) | 9 (18.4) | 1 (2.0) | 1 (2.0) | 13 (26.5) |
| Oral semaglutide 7 mg | 48 | 44 (91.7) | 5 (10.4) | 44 (91.7) | 9 (18.8) | 0 | 4 (8.3) | 10 (20.8) | |
| Oral semaglutide 14 mg | 47 | 41 (87.2) | 0 | 37 (78.7) | 7 (14.9) | 1 (2.1) | 8 (17.0) | 11 (23.4) | |
| Placebo | 50 | 44 (88.0) | 6 (12.0) | 42 (84.0) | 8 (16.0) | 2 (4.0) | 1 (2.0) | 14 (28.0) | |
| (B) | Treatment group | Patients, N | Any GI AE, n (%) | Most common GI AEs, n (%) b | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Trial (background regimen) | Nausea | Diarrhoea | Constipation | Vomiting | Abdominal distension | Abdominal discomfort | Abdominal pain upper | |||
| PIONEER 1 (diet and exercise) | Oral semaglutide 3 mg | 29 | 6 (20.7) | 2 (6.9) | 1 (3.4) | 0 | 0 | 0 | 1 (3.4) | 1 (3.4) |
| Oral semaglutide 7 mg | 29 | 2 (6.9) | 1 (3.4) | 0 | 0 | 1 (3.4) | 0 | 0 | 0 | |
| Oral semaglutide 14 mg | 28 | 9 (32.1) | 5 (17.9) | 0 | 0 | 1 (3.6) | 3 (10.7) | 2 (7.1) | 1 (3.6) | |
| Placebo | 30 | 4 (13.3) | 0 | 0 | 1 (3.3) | 0 | 0 | 0 | 1 (3.3) | |
| PIONEER 3 (metformin ± SU) | Oral semaglutide 3 mg | 52 | 23 (44.2) | 3 (5.8) | 6 (11.5) | 4 (7.7) | 2 (3.8) | 1 (1.9) | 5 (9.6) | 1 (1.9) |
| Oral semaglutide 7 mg | 52 | 25 (48.1) | 8 (15.4) | 8 (15.4) | 3 (5.8) | 2 (3.8) | 0 | 2 (3.8) | 2 (3.8) | |
| Oral semaglutide 14 mg | 51 | 33 (64.7) | 8 (15.7) | 11 (21.6) | 8 (15.7) | 6 (11.8) | 3 (5.9) | 7 (13.7) | 1 (2.0) | |
| Sitagliptin 100 mg | 52 | 20 (38.5) | 1 (1.9) | 3 (5.8) | 3 (5.8) | 1 (1.9) | 0 | 3 (5.8) | 2 (3.8) | |
| PIONEER 4 (metformin ± SGLT2i) | Oral semaglutide 14 mg | 31 | 14 (45.2) | 1 (3.2) | 0 | 7 (22.6) | 2 (6.5) | 0 | 3 (9.7) | 0 |
| Liraglutide 1.8 mg | 29 | 13 (44.8) | 6 (20.7) | 5 (17.2) | 4 (13.8) | 2 (6.9) | 1 (3.4) | 1 (3.4) | 0 | |
| Placebo | 15 | 4 (26.7) | 0 | 1 (6.7) | 2 (13.3) | 1 (6.7) | 0 | 0 | 2 (13.3) | |
| PIONEER 8 (insulin ± metformin) | Oral semaglutide 3 mg | 49 | 17 (34.7) | 5 (10.2) | 1 (2.0) | 4 (8.2) | 2 (4.1) | 1 (2.0) | 2 (4.1) | 1 (2.0) |
| Oral semaglutide 7 mg | 48 | 29 (60.4) | 8 (16.7) | 5 (10.4) | 10 (20.8) | 3 (6.3) | 3 (6.3) | 6 (12.5) | 3 (6.3) | |
| Oral semaglutide 14 mg | 47 | 27 (57.4) | 9 (19.1) | 7 (14.9) | 4 (8.5) | 6 (12.8) | 1 (2.1) | 2 (4.3) | 5 (10.6) | |
| Placebo | 50 | 21 (42.0) | 3 (6.0) | 7 (14.0) | 4 (8.0) | 2 (4.0) | 1 (2.0) | 1 (2.0) | 1 (2.0) | |
Abbreviations: AE, adverse event; BG, blood glucose; GI, gastrointestinal; n, number of patients with at least one event; N, number of randomized patients; SGLT2i, sodium‐glucose cotransporter‐2 inhibitor; SU, sulphonylurea.
a
Severe according to the American Diabetes Association classification and/or confirmed by a BG value <3.1 mmol/L (<56 mg/dL), and symptoms consistent with hypoglycaemia.
b
≥10% in any treatment group in any trial.