TABLE 2.
Key Efficacy and Safety Results from Global PIONEER Trials of Oral Semaglutide Versus Placebo or Active Comparators
| Study | Comparator | Background Regimen | Study Duration/Time of Primary End Point | ETD for Change in A1C at Time of Primary End Point, %*†‡ | ETD for Change in Body Weight at Time of Primary End Point, kg†§ | Frequency of On-Treatment AEs/Serious AEs, % | Frequency of On-Treatment GI AEs: Nausea/Diarrhea/Vomiting, % |
|---|---|---|---|---|---|---|---|
| PIONEER 1 (59) | Placebo | Diet and exercise | 26 weeks/ week 26 | 3 mg: −0.6∥ | 3 mg: −0.1 | 3 mg: 57.7/2.9 | 3 mg: 8.0/8.6/2.9 |
| 7 mg: −0.9∥ | 7 mg: −0.9 | 7 mg: 53.1/1.7 | 7 mg: 5.1/5.1/4.6 | ||||
| 14 mg: −1.1∥ | 14 mg: −2.3∥ | 14 mg: 56.6/1.1 | 14 mg: 16.0/5.1/6.9 | ||||
| Placebo: 55.6/4.5 | Placebo: 5.6/2.2/2.2 | ||||||
| PIONEER 2 (62) | Empagliflozin 25 mg/day | Metformin | 52 weeks/ week 26 | 14 mg: −0.4∥ | 14 mg: −0.1 | 14 mg: 70.5/6.6 | 14 mg: 19.8/9.3/7.3 |
| Empagliflozin: 69.2/9.0 | Empagliflozin: 2.4/3.2/1.7 | ||||||
| PIONEER 3 (63) | Sitagliptin 100 mg/day | Metformin ± sulfonylurea | 78 weeks/ week 26 | 3 mg: 0.2¶ | 3 mg: −0.6#** | 3 mg: 79.4/13.7 | 3 mg: 7.3/9.7/2.8 |
| 7 mg: −0.3∥ | 7 mg: −1.6∥ | 7 mg: 78.2/10.1 | 7 mg: 13.4/11.4/6.0 | ||||
| 14 mg: −0.5∥ | 14 mg: −2.5∥ | 14 mg: 79.6/9.5 | 14 mg: 15.1/12.3/9.0 | ||||
| Sitagliptin: 83.3/12.4 | Sitagliptin: 6.9/7.9/4.1 | ||||||
| PIONEER 4 (61) | Liraglutide 1.8 mg/day or placebo | Metformin ± SGLT2 inhibitor | 52 weeks/ week 26 | 14 mg vs. liraglutide: −0.1 | 14 mg vs. liraglutide: −1.2∥ | 14 mg: 80/11 | 14 mg: 20/15/9 |
| 14 mg vs. placebo: | 14 mg vs. placebo: | Liraglutide: 74/8 | Liraglutide: 18/11/5 | ||||
| −1.1∥ | −3.8∥ | Placebo: 67/11 | Placebo: 4/8/2 | ||||
| PIONEER 5 (moderate renal impairment††) (65) | Placebo | Metformin and/or sulfonylurea, or basal insulin ± metformin | 26 weeks/ week 26 | 14 mg: −0.8∥ | 14 mg: −2.5∥ | 14 mg: 74/10 | 14 mg: 19/10/12 |
| Placebo: 65/11 | Placebo: 7/4/1 | ||||||
| PIONEER 7 (60) | Sitagliptin 100 mg/day | 1–2 oral antidiabetic drugs: metformin, sulfonylurea, thiazolidinedione, SGLT2 inhibitor | 52 weeks/ week 52 | Flex: −0.5∥ | Flex: −1.9∥ | Flex: 78/9 | Flex: 21/9/6 |
| Sitagliptin: 69/10 | Sitagliptin: 2/3/1 | ||||||
| PIONEER 8 (64) | Add-on to insulin vs. placebo | Any basal, basal-bolus, or premixed insulin ± metformin | 52 weeks/ week 26 | 3 mg: −0.5∥ | 3 mg: −0.9# | 3 mg: 74.5/13.6 | 3 mg: 11.4/8.7/6.0 |
| 7 mg: −0.9∥ | 7 mg: −2.0∥ | 7 mg: 78.5/10.5 | 7 mg: 16.6/12.2/7.7 | ||||
| 14 mg: −1.2∥ | 14 mg: −3.3∥ | 14 mg: 83.4/6.6 | 14 mg: 23.2/14.9/9.9 | ||||
| Placebo: 75.5/9.2 | Placebo: 7.1/6.0/3.8 |
Primary end point at week 26 for all trials except PIONEER 7, for which the primary end point was proportion of patients who achieved A1C <7.0% at week 52.
Efficacy outcomes shown for the treatment policy estimand, which evaluated the treatment effect for all randomized patients regardless of trial product discontinuation or use of rescue medication.
ETD for change in A1C was statistically significant by the end of the treatment period for all trials.
Key secondary end point at week 26 (PIONEER 1–5 and 8) or week 52 (PIONEER 7).
P <0.001 in favor of oral semaglutide.
P = 0.008 in favor of sitagliptin.
P <0.05.
Because noninferiority with respect to A1C was not demonstrated for oral semaglutide 3 mg versus sitagliptin, superiority with respect to body weight was not tested.
Based on an estimated glomerular filtration rate of 30–59 mL/min/1.73 m2. AE, adverse event; ETD, estimated treatment difference; Flex, flexible dose adjustment.