parallel randomized trial
PIONEER 1
Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes Mellitus Treated With Diet and Exercise Only.
Design
Conduct and analysis
Arms
| Arm | Treatment | Background | Randomized | Analyzed | Completed treatment |
|---|---|---|---|---|---|
| A1 | Semaglutide 3 mg oral once daily (original tablet) Oral semaglutide 3 mg | diet and exercise; lifestyle: not reported | 175 | 175 | |
| A2 | Semaglutide 7 mg oral once daily (original tablet) Oral semaglutide 7 mg | diet and exercise; lifestyle: not reported | 175 | 175 | |
| A3 | Semaglutide 14 mg oral once daily (original tablet) Oral semaglutide 14 mg | diet and exercise; lifestyle: not reported | 175 | 175 | |
| A4 | Placebo Placebo | diet and exercise; lifestyle: not reported | 178 | 178 |
Baseline characteristics
As printed in the trial reports or registry, per arm or for the whole trial.
| Characteristic | Statistic | Semaglutide 3 mg oral once daily (original tablet) A1 | Semaglutide 7 mg oral once daily (original tablet) A2 | Semaglutide 14 mg oral once daily (original tablet) A3 | Placebo A4 | Whole trial ALL |
|---|---|---|---|---|---|---|
| age | mean (years) | 55 | 56 | 54 | 54 | |
| age | sd (years) | 11 | 11 | 11 | 11 | |
| asian | n | 31 | 30 | 29 | 31 | |
| black | n | 6 | 11 | 10 | 10 | |
| bmi: 25 to less than 30 | n | 198 | ||||
| bmi: 30 to less than 35 | n | 223 | ||||
| bmi: 35 or more | n | 187 | ||||
| bmi: less than 25 | n | 95 | ||||
| diabetes duration: 10 or more | n | 66 | ||||
| diabetes duration: 5 to less than 10 | n | 108 | ||||
| diabetes duration: less than 5 | n | 529 | ||||
| female | n | 86 | 82 | 89 | 89 | |
| hba1c: 8 or less | n | 409 | ||||
| hba1c: more than 8 to 9 | n | 244 | ||||
| hba1c: more than 9 | n | 50 | ||||
| hispanic | n | 52 | 31 | 46 | 51 | |
| other race american indian alaska native | n | 1 | 1 | 1 | 1 | |
| other race native hawaiian pacific islander | n | 0 | 0 | 1 | 0 | |
| other race other | n | 2 | 2 | 4 | 4 | |
| white | n | 135 | 131 | 130 | 132 |
Analyses this trial contributes to
- HbA1c changeType 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- HbA1c changeType 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- HbA1c changeType 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- HbA1c changeType 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- Body weight change in kilograms (diabetes)Type 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- Body weight change in kilograms (diabetes)Type 2 diabetes (adults); weeks 20 to 36 (target week 26); pairwise meta-analysis
- Body weight change in kilograms (diabetes)Type 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- Body weight change in kilograms (diabetes)Type 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- HbA1c below 7 percentType 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- HbA1c below 7 percentType 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- Level 2 or 3 hypoglycemia (participants)Type 2 diabetes (adults); longest follow-up; network meta-analysis
- Level 2 or 3 hypoglycemia (participants)Type 2 diabetes (adults); longest follow-up; network meta-analysis
- Systolic blood pressure changeType 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- Systolic blood pressure changeType 2 diabetes (adults); weeks 20 to 36 (target week 26); network meta-analysis
- Percent body weight changeType 2 diabetes (adults); weeks 20 to 40 (target week 26); network meta-analysis
- Percent body weight changeType 2 diabetes (adults); weeks 20 to 40 (target week 26); network meta-analysis
- Weight loss of 5 percent or moreType 2 diabetes (adults); weeks 20 to 40 (target week 26); network meta-analysis
- Weight loss of 5 percent or moreType 2 diabetes (adults); weeks 20 to 40 (target week 26); network meta-analysis
- Weight loss of 10 percent or moreType 2 diabetes (adults); weeks 20 to 40 (target week 26); network meta-analysis
- Weight loss of 10 percent or moreType 2 diabetes (adults); weeks 20 to 40 (target week 26); network meta-analysis
- SF-36 physical component summary changeType 2 diabetes (adults); weeks 20 to 130 (target week 52); network meta-analysis
- SF-36 physical component summary changeType 2 diabetes (adults); weeks 20 to 130 (target week 52); network meta-analysis
- Serious adverse eventsType 2 diabetes (adults); longest follow-up; network meta-analysis
- Serious adverse eventsType 2 diabetes (adults); longest follow-up; network meta-analysis
- NauseaType 2 diabetes (adults); longest follow-up; network meta-analysis
- NauseaType 2 diabetes (adults); longest follow-up; network meta-analysis
- VomitingType 2 diabetes (adults); longest follow-up; network meta-analysis
- VomitingType 2 diabetes (adults); longest follow-up; network meta-analysis
- DiarrheaType 2 diabetes (adults); longest follow-up; network meta-analysis
- DiarrheaType 2 diabetes (adults); longest follow-up; network meta-analysis
Results
132 adjudicated result lines, grouped by outcome. Open an outcome to see its values.
HbA1c change (32 lines; O01)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | change | -0.9 percent | 1.2 | 175 | treatment policy; full analysis; registry:outcomes | |
| 26 | A1 | change | -0.9 percent | 1.2 | 175 | hypothetical; full analysis; registry:outcomes | |
| 26 | A1 vs A4 | md | -0.7 percent | -0.9 to -0.5 | hypothetical; full analysis; registry:outcomes | ||
| 26 | A1 vs A4 | md | -0.6 percent | -0.8 to -0.4 | treatment policy; full analysis; registry:outcomes | ||
| 26 | A2 | change | -1.4 percent | 0.9 | 175 | hypothetical; full analysis; registry:outcomes | |
| 26 | A2 | change | -1.3 percent | 1.0 | 175 | treatment policy; full analysis; registry:outcomes | |
| 26 | A2 vs A4 | md | -0.9 percent | -1.1 to -0.6 | treatment policy; full analysis; registry:outcomes | ||
| 26 | A2 vs A4 | md | -1.2 percent | -1.5 to -1.0 | hypothetical; full analysis; registry:outcomes | ||
| 26 | A3 | change | -1.5 percent | 31 | hypothetical; other; age:65_or_more; R0021795:Figure 1 | ||
| 26 | A3 | change | -1.6 percent | 1.0 | 175 | hypothetical; full analysis; registry:outcomes | |
| 26 | A3 vs A4 | md | -1.4 percent | -1.7 to -1.2 | hypothetical; full analysis; registry:outcomes | ||
| 26 | A3 | change | -1.5 percent | 1.0 | 175 | treatment policy; full analysis; registry:outcomes | |
| 26 | A3 vs A4 | md | -1.1 percent | -1.3 to -0.9 | treatment policy; full analysis; registry:outcomes | ||
| 26 | A3 | change | -1.5 percent | 111 | hypothetical; other; age:45_to_65; R0021795:Figure 1 | ||
| 26 | A3 | change | -1.6 percent | 33 | hypothetical; other; age:less_than_45; R0021795:Figure 1 | ||
| 26 | A3 | change | -1.3 percent | 13 | hypothetical; other; diabetes_duration:10_or_more; R0021795:Figure 2 | ||
| 26 | A3 | change | -1.4 percent | 32 | hypothetical; other; diabetes_duration:5_to_10; R0021795:Figure 2 | ||
| 26 | A3 | change | -1.6 percent | 130 | hypothetical; other; diabetes_duration:less_than_5; R0021795:Figure 2 | ||
| 26 | A3 | change | -1.8 percent | 58 | hypothetical; other; hba1c:8.0_to_9.0; R0021795:Figure 3 | ||
| 26 | A3 | change | -2.6 percent | 16 | hypothetical; other; hba1c:9.0_or_more; R0021795:Figure 3 | ||
| 26 | A3 | change | -1.2 percent | 101 | hypothetical; other; hba1c:less_than_8.0; R0021795:Figure 3 | ||
| 26 | A4 | change | 0.3 percent | 15 | hypothetical; other; diabetes_duration:10_or_more; R0021795:Figure 2 | ||
| 26 | A4 | change | -0.1 percent | 60 | hypothetical; other; hba1c:8.0_to_9.0; R0021795:Figure 3 | ||
| 26 | A4 | change | 0.6 percent | 26 | hypothetical; other; diabetes_duration:5_to_10; R0021795:Figure 2 | ||
| 26 | A4 | change | -0.3 percent | 1.2 | 178 | treatment policy; full analysis; registry:outcomes | |
| 26 | A4 | change | 0.0 percent | 105 | hypothetical; other; hba1c:less_than_8.0; R0021795:Figure 3 | ||
| 26 | A4 | change | -0.2 percent | 111 | hypothetical; other; age:45_to_65; R0021795:Figure 1 | ||
| 26 | A4 | change | -0.3 percent | 1.2 | 178 | hypothetical; full analysis; registry:outcomes | |
| 26 | A4 | change | 0.0 percent | 33 | hypothetical; other; age:65_or_more; R0021795:Figure 1 | ||
| 26 | A4 | change | -0.3 percent | 137 | hypothetical; other; diabetes_duration:less_than_5; R0021795:Figure 2 | ||
| 26 | A4 | change | 0.1 percent | 33 | hypothetical; other; age:less_than_45; R0021795:Figure 1 | ||
| 26 | A4 | change | -0.6 percent | 9 | hypothetical; other; hba1c:9.0_or_more; R0021795:Figure 3 |
Body weight change in kilograms (diabetes) (32 lines; O02)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 vs A4 | md | -0.2 kg | -1.0 to 0.6 | hypothetical; full analysis; registry:outcomes | ||
| 26 | A1 | change | -1.8 kg | 3.3 | 175 | hypothetical; full analysis; registry:outcomes | |
| 26 | A1 | change | -1.5 kg | 3.3 | 175 | treatment policy; full analysis; registry:outcomes | |
| 26 | A1 vs A4 | md | -0.1 kg | -0.9 to 0.8 | treatment policy; full analysis; registry:outcomes | ||
| 26 | A2 vs A4 | md | -0.9 kg | -1.9 to 0.1 | treatment policy; full analysis; registry:outcomes | ||
| 26 | A2 | change | -2.6 kg | 4.1 | 175 | treatment policy; full analysis; registry:outcomes | |
| 26 | A2 vs A4 | md | -1.0 kg | -1.8 to -0.2 | hypothetical; full analysis; registry:outcomes | ||
| 26 | A2 | change | -2.8 kg | 4.0 | 175 | hypothetical; full analysis; registry:outcomes | |
| 26 | A3 | change | -4.3 kg | 4.2 | 175 | hypothetical; full analysis; registry:outcomes | |
| 26 | A3 vs A4 | md | -2.6 kg | -3.4 to -1.8 | hypothetical; full analysis; registry:outcomes | ||
| 26 | A3 | change | -4.0 kg | 4.2 | 175 | treatment policy; full analysis; registry:outcomes | |
| 26 | A3 vs A4 | md | -2.3 kg | -3.1 to -1.5 | treatment policy; full analysis; registry:outcomes | ||
| 26 | A3 | change | -4.3 kg | 111 | hypothetical; other; age:45_to_65; R0021795:Figure 1 | ||
| 26 | A3 | change | -3.2 kg | 31 | hypothetical; other; age:65_or_more; R0021795:Figure 1 | ||
| 26 | A3 | change | -4.6 kg | 33 | hypothetical; other; age:less_than_45; R0021795:Figure 1 | ||
| 26 | A3 | change | -3.6 kg | 13 | hypothetical; other; diabetes_duration:10_or_more; R0021795:Figure 2 | ||
| 26 | A3 | change | -3.8 kg | 32 | hypothetical; other; diabetes_duration:5_to_10; R0021795:Figure 2 | ||
| 26 | A3 | change | -4.3 kg | 130 | hypothetical; other; diabetes_duration:less_than_5; R0021795:Figure 2 | ||
| 26 | A3 | change | -3.7 kg | 58 | hypothetical; other; hba1c:8.0_to_9.0; R0021795:Figure 3 | ||
| 26 | A3 | change | -4.3 kg | 16 | hypothetical; other; hba1c:9.0_or_more; R0021795:Figure 3 | ||
| 26 | A3 | change | -4.4 kg | 101 | hypothetical; other; hba1c:less_than_8.0; R0021795:Figure 3 | ||
| 26 | A4 | change | -1.2 kg | 15 | hypothetical; other; diabetes_duration:10_or_more; R0021795:Figure 2 | ||
| 26 | A4 | change | -0.3 kg | 9 | hypothetical; other; hba1c:9.0_or_more; R0021795:Figure 3 | ||
| 26 | A4 | change | -1.5 kg | 60 | hypothetical; other; hba1c:8.0_to_9.0; R0021795:Figure 3 | ||
| 26 | A4 | change | -1.6 kg | 33 | hypothetical; other; age:less_than_45; R0021795:Figure 1 | ||
| 26 | A4 | change | -1.8 kg | 26 | hypothetical; other; diabetes_duration:5_to_10; R0021795:Figure 2 | ||
| 26 | A4 | change | -1.6 kg | 3.6 | 178 | hypothetical; full analysis; registry:outcomes | |
| 26 | A4 | change | -1.4 kg | 3.5 | 178 | treatment policy; full analysis; registry:outcomes | |
| 26 | A4 | change | -1.5 kg | 137 | hypothetical; other; diabetes_duration:less_than_5; R0021795:Figure 2 | ||
| 26 | A4 | change | -1.4 kg | 111 | hypothetical; other; age:45_to_65; R0021795:Figure 1 | ||
| 26 | A4 | change | -1.6 kg | 105 | hypothetical; other; hba1c:less_than_8.0; R0021795:Figure 3 | ||
| 26 | A4 | change | -1.8 kg | 33 | hypothetical; other; age:65_or_more; R0021795:Figure 1 |
HbA1c below 7 percent (4 lines; O03)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | responders | 92 / 167 | not stated; full analysis; registry:outcomes | |||
| 26 | A2 | responders | 110 / 160 | not stated; full analysis; registry:outcomes | |||
| 26 | A3 | responders | 123 / 160 | not stated; full analysis; registry:outcomes | |||
| 26 | A4 | responders | 52 / 168 | not stated; full analysis; registry:outcomes |
Level 2 or 3 hypoglycemia (participants) (4 lines; O04)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 5 / 175 | while on treatment; safety; registry:outcomes | ||||
| A2 | events | 2 / 175 | while on treatment; safety; registry:outcomes | ||||
| A3 | events | 1 / 175 | while on treatment; safety; registry:outcomes | ||||
| A4 | events | 1 / 178 | while on treatment; safety; registry:outcomes |
Systolic blood pressure change (4 lines; O05)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | change | -3 mmHg | 14 | 161 | not stated; full analysis; registry:outcomes | |
| 26 | A2 | change | -5 mmHg | 13 | 154 | not stated; full analysis; registry:outcomes | |
| 26 | A3 | change | -5 mmHg | 14 | 151 | not stated; full analysis; registry:outcomes | |
| 26 | A4 | change | -3 mmHg | 14 | 158 | not stated; full analysis; registry:outcomes |
Percent body weight change (4 lines; O10)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | percent change | -1.67 percent | 4.08 | 168 | not stated; full analysis; registry:outcomes | |
| 26 | A2 | percent change | -2.85 percent | 4.57 | 160 | not stated; full analysis; registry:outcomes | |
| 26 | A3 | percent change | -4.71 percent | 5.00 | 160 | not stated; full analysis; registry:outcomes | |
| 26 | A4 | percent change | -1.37 percent | 3.58 | 168 | not stated; full analysis; registry:outcomes |
Weight loss of 5 percent or more (4 lines; O11A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | responders | 33 / 168 | not stated; full analysis; registry:outcomes | |||
| 26 | A2 | responders | 43 / 160 | not stated; full analysis; registry:outcomes | |||
| 26 | A3 | responders | 66 / 160 | not stated; full analysis; registry:outcomes | |||
| 26 | A4 | responders | 25 / 168 | not stated; full analysis; registry:outcomes |
Weight loss of 10 percent or more (4 lines; O11B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | responders | 4 / 168 | not stated; full analysis; registry:outcomes | |||
| 26 | A2 | responders | 13 / 160 | not stated; full analysis; registry:outcomes | |||
| 26 | A3 | responders | 23 / 160 | not stated; full analysis; registry:outcomes | |||
| 26 | A4 | responders | 2 / 168 | not stated; full analysis; registry:outcomes |
All cause mortality (4 lines; O20)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 175 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 0 / 175 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 1 / 175 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 178 | not stated; safety; registry:adverse_events |
SF-36 physical component summary change (4 lines; O24A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | change | 0.52 points | 6.04 | 165 | not stated; full analysis; registry:outcomes | |
| 26 | A2 | change | 0.61 points | 5.86 | 158 | not stated; full analysis; registry:outcomes | |
| 26 | A3 | change | 0.89 points | 5.66 | 158 | not stated; full analysis; registry:outcomes | |
| 26 | A4 | change | 0.65 points | 5.44 | 167 | not stated; full analysis; registry:outcomes |
Physical functioning (any instrument) (4 lines; O24B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | change | 0.14 points | 6.25 | 165 | not stated; full analysis; registry:outcomes | |
| 26 | A2 | change | 1.18 points | 6.36 | 158 | not stated; full analysis; registry:outcomes | |
| 26 | A3 | change | 1.05 points | 5.75 | 158 | not stated; full analysis; registry:outcomes | |
| 26 | A4 | change | 0.66 points | 6.18 | 167 | not stated; full analysis; registry:outcomes |
Serious adverse events (4 lines; O25)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 5 / 175 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 3 / 175 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 2 / 175 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 8 / 178 | not stated; safety; registry:adverse_events |
Nausea (4 lines; O27A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 14 / 175 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 9 / 175 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 28 / 175 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 10 / 178 | not stated; safety; registry:adverse_events |
Vomiting (4 lines; O27B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 5 / 175 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 8 / 175 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 12 / 175 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 4 / 178 | not stated; safety; registry:adverse_events |
Diarrhea (4 lines; O27C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 15 / 175 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 9 / 175 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 9 / 175 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 4 / 178 | not stated; safety; registry:adverse_events |
Gallbladder and biliary disease (8 lines; O28)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 175 | not stated; safety; cholecystitis acute; registry:adverse_events | ||||
| A1 | events | 1 / 175 | not stated; safety; cholelithiasis; registry:adverse_events | ||||
| A2 | events | 0 / 175 | not stated; safety; cholelithiasis; registry:adverse_events | ||||
| A2 | events | 0 / 175 | not stated; safety; cholecystitis acute; registry:adverse_events | ||||
| A3 | events | 0 / 175 | not stated; safety; cholecystitis acute; registry:adverse_events | ||||
| A3 | events | 0 / 175 | not stated; safety; cholelithiasis; registry:adverse_events | ||||
| A4 | events | 0 / 178 | not stated; safety; cholecystitis acute; registry:adverse_events | ||||
| A4 | events | 0 / 178 | not stated; safety; cholelithiasis; registry:adverse_events |
Acute pancreatitis (4 lines; O29)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 175 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 0 / 175 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 175 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 178 | not stated; safety; registry:adverse_events |
Thyroid cancer (any) (4 lines; O32B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 175 | not stated; safety; papillary thyroid cancer; registry:adverse_events | ||||
| A2 | events | 0 / 175 | not stated; safety; papillary thyroid cancer; registry:adverse_events | ||||
| A3 | events | 0 / 175 | not stated; safety; papillary thyroid cancer; registry:adverse_events | ||||
| A4 | events | 0 / 178 | not stated; safety; papillary thyroid cancer; registry:adverse_events |