Table 3.
Summary of safety data across the PIONEER trials
| Trial | Treatment (n) | Adverse events (n) | Discontinuation due to adverse events % (n) | Severe hypoglycemia episodesb % (n) | |
|---|---|---|---|---|---|
| Total % (n) | Seriousa % (n) | ||||
| PIONEER 1 | Sema 3 mg (175) | 57.7 (101) | 2.9 (5) | 2.3 (4) | 0 |
| Sema 7 mg (175) | 53.1 (93) | 1.7 (3) | 4.0 (7) | 0.6 (1) | |
| Sema 14 mg (175) | 56.6 (99) | 1.1 (2) | 7.4 (13) | 0 | |
| Pbo (178) | 56.6 (99) | 4.5 (8) | 2.2 (4) | 0 | |
| PIONEER 2 | Sema 14 mg (410) | 70.5 (289) | 6.6 (27) | 10.7 (44) | 1.7 (7) |
| Empa 25 mg (409) | 69.2 (283) | 9.0 (37) | 4.4 (18) | 2.0 (8) | |
| PIONEER 3 | Sema 3 mg (466) | 79.4 (370) | 13.7 (64) | 5.6 (26) | 4.9 (23) |
| Sema 7 mg (464) | 78.2 (363) | 10.1 (47) | 5.8 (27) | 5.2 (24) | |
| Sema 14 mg (465) | 79.6 (370) | 9.5 (44) | 11.6 (54) | 7.7 (36) | |
| Sita 100 mg (466) | 83.3 (388) | 12.4 (58) | 5.2 (24) | 8.4 (39) | |
| PIONEER 4 | Sema 14 mg (285) | 80.0 (229) | 11.0 (31) | 11.0 (31) | 1.0 (2) |
| Lira 1.8 mg (284) | 74.0 (211) | 8.0 (22) | 9.0 (26) | 2.0 (7) | |
| Pbo (142) | 67.0 (95) | 11.0 (15) | 4.0 (5) | 2.0 (3) | |
| PIONEER 5 | Sema 14 mg (163) | 75.0 (122) | 12.0 (20) | 15.0 (24) | 6.0 (9) |
| Pbo (161) | 68.0 (109) | 11.0 (18) | 5.0 (8) | 2.0 (3) | |
| PIONEER 6 | Sema 14 mg (1591) | – | 18.9 (301) | 11.6 (184) | 1.4 (23) |
| Pbo (1592) | – | 22.5 (358) | 6.5 (104) | 0.8 (13) | |
| PIONEER 7 | Sema Flex (253) | 78.0 (197) | 9.0 (24) | 9.0 (22) | 0 |
| Sita 100 mg (250) | 69.0 (172) | 10.0 (24) | 3.0 (8) | 0 | |
| PIONEER 8 | Sema 3 mg (184) | 74.5 (137) | 13.6 (25) | 7.1 (13) | 28.3 (52) |
| Sema 7 mg (181) | 78.5 (142) | 10.5 (19) | 8.8 (16) | 26.0 (47) | |
| Sema 14 mg (181) | 83.4 (151) | 6.6 (12) | 13.3 (24) | 26.5 (48) | |
| Pbo (184) | 75.5 (139) | 9.2 (17) | 2.7 (5) | 29.3 (54) | |
Dula dulaglutide; Empa empagliflozin; Flex flexible dose adjustment; GI gastrointestinal; Lira liraglutide; N number; Pbo placebo; Sema oral semaglutide; Sita sitagliptin
aSerious adverse events are based on patient/event outcome or action criteria usually associated with events that pose a threat to the patient’s life or functioning
bHypoglycemic episodes were considered severe and defined as blood glucose lower than 56 mg/dL (< 3.1 mmol/L) associated with symptoms consistent with hypoglycemia (defined according to the American Diabetes Association classification)