parallel randomized trial
ADJUNCT TWO™
A 26-weeks Randomised, Insulin Capped, Placebo-controlled, Double-blind, Parallel Group, Multinational, Multi-centre Trial
Design
Conduct and analysis
Arms
| Arm | Treatment | Background | Randomized | Analyzed | Completed treatment |
|---|---|---|---|---|---|
| A1 | Liraglutide 0.6 mg subcutaneous once daily Liraglutide 0.6 mg plus insulin | basal bolus insulin capped at prerandomization dose, reduced 25 percent at randomization; lifestyle: not reported | 212 | 189 | |
| A2 | Liraglutide 1.2 mg subcutaneous once daily Liraglutide 1.2 mg plus insulin | basal bolus insulin capped at prerandomization dose, reduced 25 percent at randomization; lifestyle: not reported | 209 | 176 | |
| A3 | Liraglutide 1.8 mg subcutaneous once daily Liraglutide 1.8 mg plus insulin | basal bolus insulin capped at prerandomization dose, reduced 25 percent at randomization; lifestyle: not reported | 207 | 170 | |
| A4 | Placebo Placebo plus insulin | basal bolus insulin capped at prerandomization dose, reduced 25 percent at randomization; lifestyle: not reported | 207 | 190 |
Baseline characteristics
As printed in the trial reports or registry, per arm or for the whole trial.
| Characteristic | Statistic | Liraglutide 0.6 mg subcutaneous once daily A1 | Liraglutide 1.2 mg subcutaneous once daily A2 | Liraglutide 1.8 mg subcutaneous once daily A3 | Placebo A4 |
|---|---|---|---|---|---|
| age | mean (years) | 43.9 | 42.8 | 43.2 | 42.7 |
| age | sd (years) | 12.88 | 13.31 | 12.9 | 12.97 |
| female | n | 118 | 106 | 113 | 112 |
| hba1c | mean (percent) | 8.09 | 8.07 | 8.04 | 8.12 |
| hba1c | sd (percent) | 0.743 | 0.731 | 0.736 | 0.723 |
| weight | mean (kg) | 83.10 | 84.69 | 83.64 | 84.20 |
| weight | sd (kg) | 16.137 | 18.155 | 17.620 | 16.539 |
Analyses this trial contributes to
- HbA1c changeType 1 diabetes; weeks 12 to 40 (target week 26); network meta-analysis
- HbA1c changeType 1 diabetes; weeks 12 to 40 (target week 26); network meta-analysis
- Serious adverse eventsType 1 diabetes; longest follow-up; network meta-analysis
- Serious adverse eventsType 1 diabetes; longest follow-up; network meta-analysis
- NauseaType 1 diabetes; longest follow-up; network meta-analysis
- NauseaType 1 diabetes; longest follow-up; pairwise meta-analysis
- VomitingType 1 diabetes; longest follow-up; network meta-analysis
- VomitingType 1 diabetes; longest follow-up; pairwise meta-analysis
- DiarrheaType 1 diabetes; longest follow-up; pairwise meta-analysis
- DiarrheaType 1 diabetes; longest follow-up; network meta-analysis
- ConstipationType 1 diabetes; longest follow-up; pairwise meta-analysis
- ConstipationType 1 diabetes; longest follow-up; network meta-analysis
Results
77 adjudicated result lines, grouped by outcome. Open an outcome to see its values.
HbA1c change (7 lines; O01)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 vs A4 | md | -0.24 percent | -0.39 to -0.1 | not stated; full analysis; registry:outcomes | ||
| 26 | A1 | change | -0.23 percent | 0.744 | 189 | not stated; full analysis; registry:outcomes | |
| 26 | A2 | change | -0.23 percent | 0.731 | 176 | not stated; full analysis; registry:outcomes | |
| 26 | A2 vs A4 | md | -0.23 percent | -0.38 to -0.08 | not stated; full analysis; registry:outcomes | ||
| 26 | A3 vs A4 | md | -0.35 percent | -0.5 to -0.2 | not stated; full analysis; registry:outcomes | ||
| 26 | A3 | change | -0.32 percent | 0.73 | 170 | not stated; full analysis; registry:outcomes | |
| 26 | A4 | change | 0.01 percent | 0.674 | 190 | not stated; full analysis; registry:outcomes |
Level 2 or 3 hypoglycemia (episode rate) (1 lines; O04B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A2 vs A4 | rate ratio | 1.3 | while on treatment; safety; R0008931:Results |
Total daily insulin dose change (1 lines; O06)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A3 vs A4 | md | -10 percent | not stated; full analysis; R0008931:Results |
Acute kidney injury (4 lines; O121)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 211 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 1 / 209 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 206 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 206 | not stated; safety; registry:adverse_events |
Serious adverse events (4 lines; O25)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 20 / 211 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 21 / 209 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 14 / 206 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 14 / 206 | not stated; safety; registry:adverse_events |
Discontinuation due to adverse events (4 lines; O26)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 12 / 212 | not stated; randomized; registry:flow | ||||
| A2 | events | 19 / 209 | not stated; randomized; registry:flow | ||||
| A3 | events | 34 / 207 | not stated; randomized; registry:flow | ||||
| A4 | events | 2 / 207 | not stated; randomized; registry:flow |
Nausea (8 lines; O27A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 211 | not stated; safety; registry:adverse_events | ||||
| A1 | events | 68 / 211 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 1 / 209 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 97 / 209 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 102 / 206 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 206 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 34 / 206 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 206 | not stated; safety; registry:adverse_events |
Vomiting (8 lines; O27B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 19 / 211 | not stated; safety; registry:adverse_events | ||||
| A1 | events | 0 / 211 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 29 / 209 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 2 / 209 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 35 / 206 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 206 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 7 / 206 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 1 / 206 | not stated; safety; registry:adverse_events |
Diarrhea (8 lines; O27C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 211 | not stated; safety; registry:adverse_events | ||||
| A1 | events | 14 / 211 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 25 / 209 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 2 / 209 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 30 / 206 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 206 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 17 / 206 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 206 | not stated; safety; registry:adverse_events |
Constipation (4 lines; O27D)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 6 / 211 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 23 / 209 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 14 / 206 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 9 / 206 | 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 | 0 / 211 | not stated; safety; bile duct stone; registry:adverse_events | ||||
| A1 | events | 0 / 211 | not stated; safety; cholecystitis; registry:adverse_events | ||||
| A2 | events | 0 / 209 | not stated; safety; cholecystitis; registry:adverse_events | ||||
| A2 | events | 0 / 209 | not stated; safety; bile duct stone; registry:adverse_events | ||||
| A3 | events | 0 / 206 | not stated; safety; bile duct stone; registry:adverse_events | ||||
| A3 | events | 0 / 206 | not stated; safety; cholecystitis; registry:adverse_events | ||||
| A4 | events | 1 / 206 | not stated; safety; cholecystitis; registry:adverse_events | ||||
| A4 | events | 1 / 206 | not stated; safety; bile duct stone; registry:adverse_events |
Diabetic ketoacidosis (4 lines; O30)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 211 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 1 / 209 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 206 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 206 | not stated; safety; registry:adverse_events |
Severe hypoglycemia (type 1 diabetes) (12 lines; O31)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 5 / 211 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A1 | events | 0 / 211 | not stated; safety; hypoglycaemic coma; registry:adverse_events | ||||
| A1 | events | 3 / 211 | not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events | ||||
| A2 | events | 2 / 209 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A2 | events | 1 / 209 | not stated; safety; hypoglycaemic coma; registry:adverse_events | ||||
| A2 | events | 6 / 209 | not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events | ||||
| A3 | events | 1 / 206 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A3 | events | 0 / 206 | not stated; safety; hypoglycaemic coma; registry:adverse_events | ||||
| A3 | events | 2 / 206 | not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events | ||||
| A4 | events | 1 / 206 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A4 | events | 0 / 206 | not stated; safety; hypoglycaemic coma; registry:adverse_events | ||||
| A4 | events | 1 / 206 | not stated; safety; hypoglycaemic unconsciousness; 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 / 211 | not stated; safety; volvulus; registry:adverse_events | ||||
| A2 | events | 0 / 209 | not stated; safety; volvulus; registry:adverse_events | ||||
| A3 | events | 1 / 206 | not stated; safety; volvulus; registry:adverse_events | ||||
| A4 | events | 0 / 206 | not stated; safety; volvulus; registry:adverse_events |