Table 1.
Summary of design and primary endpoints across the PIONEER trials considering trial product without rescue medication (trial product estimand)
| Trial | Populationa | Primary endpoint | Treatment | Results primary endpoint (%) | EDT (95% CI) | p |
|---|---|---|---|---|---|---|
| PIONEER 1 | 703 adults with T2D uncontrolled with diet and exercise | Change in HbA1c from baseline to week 26 | Sema 3 mg | − 0.8 | − 0.7% (− 0.9 to − 0.5) | < 0.001 |
| Sema 7 mg | − 1.3 | − 1.2% (− 1.5 to − 1.0) | < 0.001 | |||
| Sema 14 mg | − 1.5 | − 1.4% (− 1.7 to − 1.2) | < 0.001 | |||
| Pbo | − 0.1 | – | – | |||
| PIONEER 2 | 822 adults with T2D uncontrolled on metformin | Change in HbA1c from baseline to week 26 | Sema 14 mg | − 1.4 | − 0.5% (− 0.7 to − 0.4) | < 0.0001 |
| Empa 25 mg | − 0.9 | – | – | |||
| PIONEER 3 | 1864 adults with T2D uncontrolled with metformin and/or sulfonylurea | Change in HbA1c from baseline to week 26 | Sema 3 mg | − 0.5 | 0.2% (0.1–0.4) | < 0.001 |
| Sema 7 mg | − 1.1 | − 0.3% (− 0.4 to − 0.2) | < 0.001 | |||
| Sema 14 mg | − 1.4 | − 0.6% (− 0.7 to − 0.5) | < 0.001 | |||
| Sita 100 mg | − 0.8 | – | – | |||
| PIONEER 4 | 711 adults with T2D on metformin with or without an SGLT2 inhibitor | Change in HbA1c from baseline to week 26 | Sema 14 mg | − 1.3 | − 0.2% (− 0.3 to − 0.1)b | 0.0056b |
| − 1.2% (− 1.4 to − 1.0)c | < 0.001c | |||||
| Lira 1.8 mg | − 1.1 | – | – | |||
| Pbo | − 0.1 | – | – | |||
| PIONEER 5 | 324 adults with T2D and moderate renal impairment on metformin and/or sulfonylurea, or basal insulin | Change in HbA1c from baseline to week 26 | Sema 14 mg | − 1.1 | 1.0% (− 1.2 to − 0.8) | < 0.0001 |
| Pbo | − 0.1 | – | – | |||
| PIONEER 7 | 504 adults with T2D inadequately controlled on one of two oral glucose-lowering drugs | Proportion of patients with HbA1c less than 7.0% at week 52 | Sema flex | 63 | – | < 0.0001 |
| Sita 100 mg | 28 | – | – | |||
| PIONEER 8 | 731 adults with T2D under insulin therapy with or without metformin | Change in HbA1c from baseline to week 26 | Sema 3 mg | − 0.6 | − 0.6 (− 0.7 to − 0.4) | < 0.0001 |
| Sema 7 mg | − 1.0 | − 1.0 (− 1.2 to − 0.8) | < 0.0001 | |||
| Sema 14 mg | − 1.4 | − 1.4 (− 1.6 to − 1.2) | < 0.0001 | |||
| Pbo | − 0.0 | – | – |
CI confidence interval; Dula dulaglutide; EDT estimated treatment differences; Empa empagliflozin; Flex flexible dose (3, 7 or 14 mg); Lira liraglutide; Pbo placebo; Sema oral semaglutide; Sita sitagliptin; T2D type 2 diabetes
aRandomized
bVersus liraglutide
cVersus placebo