parallel randomized trial
SUSTAIN™ 2
Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin and/or TZD in Subjects With Type 2 Diabetes (SUSTAIN™ 2 - vs. DPP-4 Inhibitor)
Design
Conduct and analysis
Arms
| Arm | Treatment | Background | Randomized | Analyzed | Completed treatment |
|---|---|---|---|---|---|
| A1 | Semaglutide 0.5 mg subcutaneous once weekly Semaglutide 0.5 mg plus sitagliptin placebo | metformin and/or thiazolidinedione; lifestyle: not reported | 409 | ||
| A2 | Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg plus sitagliptin placebo | metformin and/or thiazolidinedione; lifestyle: not reported | 409 | ||
| A3 | Sitagliptin Sitagliptin 100 mg plus semaglutide placebo | metformin and/or thiazolidinedione; lifestyle: not reported | 407 |
Baseline characteristics
As printed in the trial reports or registry, per arm or for the whole trial.
| Characteristic | Statistic | Semaglutide 0.5 mg subcutaneous once weekly A1 | Semaglutide 1.0 mg subcutaneous once weekly A2 | Sitagliptin A3 | Whole trial ALL |
|---|---|---|---|---|---|
| age | mean (years) | 54.8 | 56.0 | 54.6 | |
| age | sd (years) | 10.2 | 9.4 | 10.4 | |
| asian | n | 307 | |||
| asian | percent | 25.1 | |||
| black | n | 59 | |||
| black | percent | 4.8 | |||
| bmi | mean (kg/m2) | 32.5 | |||
| bmi | sd (kg/m2) | 6.2 | |||
| diabetes duration | mean (years) | 6.6 | |||
| diabetes duration | sd (years) | 5.1 | |||
| egfr | mean (mL/min/1.73 m2) | 97.5 | |||
| egfr | sd (mL/min/1.73 m2) | 22.4 | |||
| female | n | 202 | 204 | 199 | |
| female | percent | 49.4 | |||
| hba1c | mean (percent) | 8.01 | 8.04 | 8.17 | |
| hba1c | sd (percent) | 0.92 | 0.93 | 0.92 | |
| other metformin alone | percent | 94.0 | |||
| other race other | n | 20 | |||
| other retinopathy history | n | 94 | |||
| other retinopathy history | percent | 7.7 | |||
| sbp | mean (mmHg) | 132.73 | 132.56 | 132.66 | |
| sbp | sd (mmHg) | 16.09 | 13.93 | 14.58 | |
| weight | mean (kg) | 89.93 | 89.21 | 89.29 | |
| weight | sd (kg) | 20.39 | 20.74 | 19.67 | |
| white | n | 839 | |||
| white | percent | 68.5 |
Analyses this trial contributes to
- HbA1c changeType 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- HbA1c changeType 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- Body weight change in kilograms (diabetes)Type 2 diabetes (adults); weeks 36 to 64 (target week 52); network meta-analysis
- Body weight change in kilograms (diabetes)Type 2 diabetes (adults); weeks 36 to 64 (target week 52); 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 36 to 64 (target week 52); network meta-analysis
- Systolic blood pressure changeType 2 diabetes (adults); weeks 36 to 64 (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
- Discontinuation due to adverse eventsType 2 diabetes (adults); longest follow-up; network meta-analysis
- Discontinuation due to adverse eventsType 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
- DiarrheaType 2 diabetes (adults); longest follow-up; network meta-analysis
- ConstipationType 2 diabetes (adults); longest follow-up; network meta-analysis
- Discontinuation due to gastrointestinal adverse eventsType 2 diabetes (adults); longest follow-up; network meta-analysis
- Discontinuation due to gastrointestinal adverse eventsType 2 diabetes (adults); longest follow-up; network meta-analysis
Results
84 adjudicated result lines, grouped by outcome. Open an outcome to see its values.
HbA1c change (5 lines; O01)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 56 | A1 vs A3 | md | -0.92 percent | -1.21 to -0.62 | not stated; full analysis; registry:outcomes | ||
| 56 | A1 | change | -1.32 percent | 0.05 | 409 | not stated; full analysis; registry:outcomes | |
| 56 | A2 | change | -1.61 percent | 0.05 | 409 | not stated; full analysis; registry:outcomes | |
| 56 | A2 vs A3 | md | -1.06 percent | -1.21 to -0.91 | not stated; full analysis; registry:outcomes | ||
| 56 | A3 | change | -0.55 percent | 0.05 | 407 | not stated; full analysis; registry:outcomes |
Body weight change in kilograms (diabetes) (3 lines; O02)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 56 | A1 | change | -4.28 kg | 0.25 | 409 | not stated; full analysis; registry:outcomes | |
| 56 | A2 | change | -6.13 kg | 0.25 | 409 | not stated; full analysis; registry:outcomes | |
| 56 | A3 | change | -1.93 kg | 0.26 | 407 | not stated; full analysis; registry:outcomes |
Level 2 or 3 hypoglycemia (participants) (3 lines; O04)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 409 | while on treatment; safety; R0021710:Table 2 | ||||
| A2 | events | 0 / 409 | while on treatment; safety; R0021710:Table 2 | ||||
| A3 | events | 2 / 407 | while on treatment; safety; R0021710:Table 2 |
Systolic blood pressure change (3 lines; O05)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 56 | A1 | change | -5.07 mmHg | 0.64 | 409 | not stated; full analysis; registry:outcomes | |
| 56 | A2 | change | -5.61 mmHg | 0.63 | 409 | not stated; full analysis; registry:outcomes | |
| 56 | A3 | change | -2.29 mmHg | 0.67 | 407 | not stated; full analysis; registry:outcomes |
All cause mortality (3 lines; O20)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 2 / 409 | not stated; full analysis; registry:flow | ||||
| A2 | events | 1 / 409 | not stated; full analysis; registry:flow | ||||
| A3 | events | 3 / 407 | not stated; full analysis; registry:flow |
Health related quality of life total score (any instrument) (6 lines; O24C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 56 | A1 | change | 5.3 points | not stated; full analysis; R0012485:Figure 1 | |||
| 56 | A1 | change | 5.28 points | 0.23 | 333 | not stated; full analysis; registry:outcomes | |
| 56 | A2 | change | 5.9 points | not stated; full analysis; R0012485:Figure 1 | |||
| 56 | A2 | change | 5.91 points | 0.23 | 333 | not stated; full analysis; registry:outcomes | |
| 56 | A3 | change | 4.5 points | not stated; full analysis; R0012485:Figure 1 | |||
| 56 | A3 | change | 4.45 points | 0.24 | 294 | not stated; full analysis; registry:outcomes |
Serious adverse events (3 lines; O25)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 30 / 409 | while on treatment; safety; R0021710:Table 2 | ||||
| A2 | events | 30 / 409 | while on treatment; safety; R0021710:Table 2 | ||||
| A3 | events | 29 / 407 | while on treatment; safety; R0021710:Table 2 |
Discontinuation due to adverse events (3 lines; O26)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 33 / 409 | while on treatment; safety; R0021710:Table 2 | ||||
| A2 | events | 39 / 409 | while on treatment; safety; R0021710:Table 2 | ||||
| A3 | events | 12 / 407 | while on treatment; safety; R0021710:Table 2 |
Nausea (4 lines; O27A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 73 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 72 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 17 / 203 | while on treatment; safety; placebo_volume:0.5mg; registry:adverse_events | ||||
| A3 | events | 13 / 204 | while on treatment; safety; placebo_volume:1.0mg; registry:adverse_events |
Vomiting (4 lines; O27B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 33 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 41 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 5 / 203 | while on treatment; safety; placebo_volume:0.5mg; registry:adverse_events | ||||
| A3 | events | 6 / 204 | while on treatment; safety; placebo_volume:1.0mg; registry:adverse_events |
Diarrhea (8 lines; O27C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 53 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A1 | events | 1 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 53 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 0 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 0 / 203 | while on treatment; safety; placebo_volume:0.5mg; registry:adverse_events | ||||
| A3 | events | 16 / 203 | while on treatment; safety; placebo_volume:0.5mg; registry:adverse_events | ||||
| A3 | events | 13 / 204 | while on treatment; safety; placebo_volume:1.0mg; registry:adverse_events | ||||
| A3 | events | 0 / 204 | while on treatment; safety; placebo_volume:1.0mg; registry:adverse_events |
Constipation (4 lines; O27D)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 18 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 23 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 3 / 203 | while on treatment; safety; placebo_volume:0.5mg; registry:adverse_events | ||||
| A3 | events | 5 / 204 | while on treatment; safety; placebo_volume:1.0mg; registry:adverse_events |
Discontinuation due to gastrointestinal adverse events (3 lines; O27E)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 27 / 409 | while on treatment; safety; R0021710:Table 2 | ||||
| A2 | events | 31 / 409 | while on treatment; safety; R0021710:Table 2 | ||||
| A3 | events | 3 / 407 | while on treatment; safety; R0021710:Table 2 |
Gallbladder and biliary disease (12 lines; O28)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 409 | while on treatment; safety; cholecystitis acute; registry:adverse_events | ||||
| A1 | events | 0 / 409 | while on treatment; safety; cholecystitis; registry:adverse_events | ||||
| A1 | events | 1 / 409 | while on treatment; safety; cholelithiasis; registry:adverse_events | ||||
| A2 | events | 2 / 409 | while on treatment; safety; cholecystitis acute; registry:adverse_events | ||||
| A2 | events | 1 / 409 | while on treatment; safety; cholecystitis; registry:adverse_events | ||||
| A2 | events | 2 / 409 | while on treatment; safety; cholelithiasis; registry:adverse_events | ||||
| A3 | events | 0 / 204 | while on treatment; safety; placebo_volume:1.0mg; cholecystitis acute; registry:adverse_events | ||||
| A3 | events | 0 / 204 | while on treatment; safety; placebo_volume:1.0mg; cholecystitis; registry:adverse_events | ||||
| A3 | events | 0 / 203 | while on treatment; safety; placebo_volume:0.5mg; cholecystitis acute; registry:adverse_events | ||||
| A3 | events | 0 / 204 | while on treatment; safety; placebo_volume:1.0mg; cholelithiasis; registry:adverse_events | ||||
| A3 | events | 1 / 203 | while on treatment; safety; placebo_volume:0.5mg; cholelithiasis; registry:adverse_events | ||||
| A3 | events | 0 / 203 | while on treatment; safety; placebo_volume:0.5mg; cholecystitis; registry:adverse_events |
Acute pancreatitis (12 lines; O29)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A1 | events | 1 / 409 | while on treatment; safety; pancreatitis necrotising; registry:adverse_events | ||||
| A1 | events | 2 / 409 | while on treatment; safety; pancreatitis; registry:adverse_events | ||||
| A2 | events | 0 / 409 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 0 / 409 | while on treatment; safety; pancreatitis necrotising; registry:adverse_events | ||||
| A2 | events | 0 / 409 | while on treatment; safety; pancreatitis; registry:adverse_events | ||||
| A3 | events | 0 / 203 | while on treatment; safety; placebo_volume:0.5mg; registry:adverse_events | ||||
| A3 | events | 0 / 203 | while on treatment; safety; placebo_volume:0.5mg; pancreatitis necrotising; registry:adverse_events | ||||
| A3 | events | 0 / 203 | while on treatment; safety; placebo_volume:0.5mg; pancreatitis; registry:adverse_events | ||||
| A3 | events | 0 / 204 | while on treatment; safety; placebo_volume:1.0mg; registry:adverse_events | ||||
| A3 | events | 0 / 204 | while on treatment; safety; placebo_volume:1.0mg; pancreatitis necrotising; registry:adverse_events | ||||
| A3 | events | 0 / 204 | while on treatment; safety; placebo_volume:1.0mg; pancreatitis; registry:adverse_events |
Thyroid cancer (any) (4 lines; O32B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 409 | while on treatment; safety; papillary thyroid cancer; registry:adverse_events | ||||
| A2 | events | 1 / 409 | while on treatment; safety; papillary thyroid cancer; registry:adverse_events | ||||
| A3 | events | 0 / 203 | while on treatment; safety; placebo_volume:0.5mg; papillary thyroid cancer; registry:adverse_events | ||||
| A3 | events | 0 / 204 | while on treatment; safety; placebo_volume:1.0mg; papillary thyroid cancer; registry:adverse_events |
Intestinal obstruction or ileus (4 lines; O37B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 409 | while on treatment; safety; intestinal obstruction; registry:adverse_events | ||||
| A2 | events | 1 / 409 | while on treatment; safety; intestinal obstruction; registry:adverse_events | ||||
| A3 | events | 0 / 203 | while on treatment; safety; placebo_volume:0.5mg; intestinal obstruction; registry:adverse_events | ||||
| A3 | events | 0 / 204 | while on treatment; safety; placebo_volume:1.0mg; intestinal obstruction; registry:adverse_events |