parallel randomized trial
ADJUNCT ONE™
The Efficacy and Safety of Liraglutide as Adjunct Therapy to Insulin in the Treatment of Type 1 Diabetes. A 52-week Randomised, Treat-to-target, Placebo-controlled, Double Blinded, 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 | CSII or basal bolus insulin titrated treat to target, reduced 25 percent at randomization; lifestyle: not reported | 351 | 334 | |
| A2 | Liraglutide 1.2 mg subcutaneous once daily Liraglutide 1.2 mg plus insulin | CSII or basal bolus insulin titrated treat to target, reduced 25 percent at randomization; lifestyle: not reported | 350 | 312 | |
| A3 | Liraglutide 1.8 mg subcutaneous once daily Liraglutide 1.8 mg plus insulin | CSII or basal bolus insulin titrated treat to target, reduced 25 percent at randomization; lifestyle: not reported | 349 | 305 | |
| A4 | Placebo Placebo plus insulin | CSII or basal bolus insulin titrated treat to target, reduced 25 percent at randomization; lifestyle: not reported | 348 | 324 |
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) | 43.6 | 43.9 | 43.7 | 43.4 |
| age | sd (years) | 12.78 | 13.06 | 13.33 | 12.57 |
| female | n | 186 | 179 | 181 | 180 |
| hba1c | mean (percent) | 8.18 | 8.16 | 8.14 | 8.15 |
| hba1c | sd (percent) | 0.738 | 0.779 | 0.740 | 0.728 |
| weight | mean (kg) | 86.54 | 85.39 | 86.27 | 86.41 |
| weight | sd (kg) | 17.338 | 17.210 | 17.321 | 17.768 |
Analyses this trial contributes to
- HbA1c changeType 1 diabetes; weeks 12 to 40 (target week 26); descriptive only
- HbA1c changeType 1 diabetes; weeks 12 to 40 (target week 26); descriptive only
- HbA1c changeType 1 diabetes; weeks 40 to 64 (target week 52); descriptive only
- HbA1c changeType 1 diabetes; weeks 40 to 64 (target week 52); descriptive only
- Total daily insulin dose changeType 1 diabetes; weeks 40 to 64 (target week 52); descriptive only
- Total daily insulin dose changeType 1 diabetes; weeks 40 to 64 (target week 52); descriptive only
- Total daily insulin dose changeType 1 diabetes; weeks 12 to 40 (target week 26); descriptive only
- Total daily insulin dose changeType 1 diabetes; weeks 12 to 40 (target week 26); descriptive only
- 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; network meta-analysis
- DiarrheaType 1 diabetes; longest follow-up; pairwise meta-analysis
- ConstipationType 1 diabetes; longest follow-up; pairwise meta-analysis
- ConstipationType 1 diabetes; longest follow-up; network meta-analysis
Results
118 adjudicated result lines, grouped by outcome. Open an outcome to see its values.
HbA1c change (14 lines; O01)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | change | -0.59 percent | while on treatment; full analysis; R0008931:Supplement Table S1 | |||
| 26 | A1 vs A4 | md | -0.11 percent | -0.22 to -0.01 | while on treatment; full analysis; R0008931:Supplement Table S1 | ||
| 26 | A2 | change | -0.72 percent | while on treatment; full analysis; R0008931:Supplement Table S1 | |||
| 26 | A2 vs A4 | md | -0.24 percent | -0.36 to -0.13 | while on treatment; full analysis; R0008931:Supplement Table S1 | ||
| 26 | A3 | change | -0.78 percent | while on treatment; full analysis; R0008931:Supplement Table S1 | |||
| 26 | A3 vs A4 | md | -0.30 percent | -0.41 to -0.19 | while on treatment; full analysis; R0008931:Supplement Table S1 | ||
| 26 | A4 | change | -0.48 percent | while on treatment; full analysis; R0008931:Supplement Table S1 | |||
| 52 | A1 | change | -0.45 percent | 0.741 | 334 | not stated; full analysis; registry:outcomes | |
| 52 | A1 vs A4 | md | -0.09 percent | -0.21 to 0.03 | not stated; full analysis; registry:outcomes | ||
| 52 | A2 | change | -0.50 percent | 0.767 | 312 | not stated; full analysis; registry:outcomes | |
| 52 | A2 vs A4 | md | -0.15 percent | -0.27 to -0.03 | not stated; full analysis; registry:outcomes | ||
| 52 | A3 | change | -0.54 percent | 0.729 | 305 | not stated; full analysis; registry:outcomes | |
| 52 | A3 vs A4 | md | -0.20 percent | -0.32 to -0.07 | not stated; full analysis; registry:outcomes | ||
| 52 | A4 | change | -0.34 percent | 0.707 | 324 | 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 | 80 | 281 / | while on treatment; safety; R0008931:Supplement Table S2 | |||
| A2 | events | 84 | 291 / | while on treatment; safety; R0008931:Supplement Table S2 | |||
| A3 | events | 86 | 299 / | while on treatment; safety; R0008931:Supplement Table S2 | |||
| A4 | events | 81 | 282 / | while on treatment; safety; R0008931:Supplement Table S2 |
Level 2 or 3 hypoglycemia (episode rate) (6 lines; O04B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 vs A4 | rate ratio | 1.17 | 0.97 to 1.43 | not stated; safety; registry:outcomes | |||
| A1 vs A4 | rate ratio | 1.18 | 0.97 to 1.43 | while on treatment; safety; R0008931:Supplement Table S2 | |||
| A2 vs A4 | rate ratio | 1.29 | 1.06 to 1.57 | while on treatment; safety; R0008931:Supplement Table S2 | |||
| A2 vs A4 | rate ratio | 1.27 | 1.03 to 1.55 | not stated; safety; registry:outcomes | |||
| A3 vs A4 | rate ratio | 1.34 | 1.10 to 1.63 | while on treatment; safety; R0008931:Supplement Table S2 | |||
| A3 vs A4 | rate ratio | 1.31 | 1.07 to 1.59 | not stated; safety; registry:outcomes |
Total daily insulin dose change (10 lines; O06)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | percent change | -2 percent | while on treatment; full analysis; R0008931:Supplement Table S1 | |||
| 26 | A1 vs A4 | md | -4 percent | -8 to 0 | while on treatment; full analysis; R0008931:Supplement Table S1 | ||
| 26 | A2 | percent change | -6 percent | while on treatment; full analysis; R0008931:Supplement Table S1 | |||
| 26 | A2 vs A4 | md | -8 percent | -12 to -4 | while on treatment; full analysis; R0008931:Supplement Table S1 | ||
| 26 | A3 vs A4 | md | -12 percent | -16 to -9 | while on treatment; full analysis; R0008931:Supplement Table S1 | ||
| 26 | A3 | percent change | -10 percent | while on treatment; full analysis; R0008931:Supplement Table S1 | |||
| 26 | A4 | percent change | 2 percent | while on treatment; full analysis; R0008931:Supplement Table S1 | |||
| 52 | A1 vs A4 | md | 1.00 ratio | 0.96 to 1.04 | not stated; full analysis; registry:outcomes | ||
| 52 | A2 vs A4 | md | 0.95 ratio | 0.91 to 0.99 | not stated; full analysis; registry:outcomes | ||
| 52 | A3 vs A4 | md | 0.92 ratio | 0.88 to 0.96 | not stated; full analysis; registry:outcomes |
Acute kidney injury (4 lines; O121)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 350 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 0 / 348 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 1 / 348 | 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 | 35 / 350 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 36 / 348 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 29 / 347 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 38 / 348 | 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 | 15 / 351 | not stated; randomized; registry:flow | ||||
| A2 | events | 41 / 350 | not stated; randomized; registry:flow | ||||
| A3 | events | 49 / 349 | not stated; randomized; registry:flow | ||||
| A4 | events | 14 / 348 | not stated; randomized; registry:flow |
Nausea (8 lines; O27A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 112 / 350 | not stated; safety; registry:adverse_events | ||||
| A1 | events | 1 / 350 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 141 / 348 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 1 / 348 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 172 / 347 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 42 / 348 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 348 | not stated; safety; registry:adverse_events |
Vomiting (8 lines; O27B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 24 / 350 | not stated; safety; registry:adverse_events | ||||
| A1 | events | 0 / 350 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 44 / 348 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 1 / 348 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 64 / 347 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 21 / 348 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 348 | not stated; safety; registry:adverse_events |
Diarrhea (4 lines; O27C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 41 / 350 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 50 / 348 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 64 / 347 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 38 / 348 | not stated; safety; registry:adverse_events |
Constipation (4 lines; O27D)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 17 / 350 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 28 / 348 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 26 / 347 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 9 / 348 | not stated; safety; registry:adverse_events |
Gallbladder and biliary disease (12 lines; O28)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 350 | not stated; safety; cholecystitis acute; registry:adverse_events | ||||
| A1 | events | 0 / 350 | not stated; safety; cholecystitis; registry:adverse_events | ||||
| A1 | events | 0 / 350 | not stated; safety; cholelithiasis; registry:adverse_events | ||||
| A2 | events | 0 / 348 | not stated; safety; cholecystitis acute; registry:adverse_events | ||||
| A2 | events | 1 / 348 | not stated; safety; cholecystitis; registry:adverse_events | ||||
| A2 | events | 1 / 348 | not stated; safety; cholelithiasis; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; cholecystitis acute; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; cholecystitis; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; cholelithiasis; registry:adverse_events | ||||
| A4 | events | 0 / 348 | not stated; safety; cholecystitis acute; registry:adverse_events | ||||
| A4 | events | 0 / 348 | not stated; safety; cholelithiasis; registry:adverse_events | ||||
| A4 | events | 0 / 348 | not stated; safety; cholecystitis; registry:adverse_events |
Acute pancreatitis (4 lines; O29)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 350 | not stated; safety; pancreatitis; registry:adverse_events | ||||
| A2 | events | 0 / 348 | not stated; safety; pancreatitis; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; pancreatitis; registry:adverse_events | ||||
| A4 | events | 0 / 348 | not stated; safety; pancreatitis; registry:adverse_events |
Diabetic ketoacidosis (4 lines; O30)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 3 / 350 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 1 / 348 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 3 / 347 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 348 | 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 | 3 / 350 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A1 | events | 1 / 350 | not stated; safety; hypoglycaemic seizure; registry:adverse_events | ||||
| A1 | events | 5 / 350 | not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events | ||||
| A2 | events | 7 / 348 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A2 | events | 1 / 348 | not stated; safety; hypoglycaemic seizure; registry:adverse_events | ||||
| A2 | events | 3 / 348 | not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events | ||||
| A3 | events | 5 / 347 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; hypoglycaemic seizure; registry:adverse_events | ||||
| A3 | events | 6 / 347 | not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events | ||||
| A4 | events | 13 / 348 | not stated; safety; hypoglycaemia; registry:adverse_events | ||||
| A4 | events | 0 / 348 | not stated; safety; hypoglycaemic seizure; registry:adverse_events | ||||
| A4 | events | 6 / 348 | not stated; safety; hypoglycaemic unconsciousness; registry:adverse_events |
Thyroid cancer (any) (4 lines; O32B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 350 | not stated; safety; papillary thyroid cancer; registry:adverse_events | ||||
| A2 | events | 0 / 348 | not stated; safety; papillary thyroid cancer; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; papillary thyroid cancer; registry:adverse_events | ||||
| A4 | events | 1 / 348 | not stated; safety; papillary thyroid cancer; registry:adverse_events |
Suicidal ideation or behavior (8 lines; O35A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 350 | not stated; safety; depression suicidal; registry:adverse_events | ||||
| A1 | events | 1 / 350 | not stated; safety; suicide attempt; registry:adverse_events | ||||
| A2 | events | 0 / 348 | not stated; safety; depression suicidal; registry:adverse_events | ||||
| A2 | events | 0 / 348 | not stated; safety; suicide attempt; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; depression suicidal; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; suicide attempt; registry:adverse_events | ||||
| A4 | events | 0 / 348 | not stated; safety; depression suicidal; registry:adverse_events | ||||
| A4 | events | 1 / 348 | not stated; safety; suicide attempt; registry:adverse_events |
Death by suicide (4 lines; O35B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 350 | not stated; safety; registry:adverse_events | ||||
| A2 | events | 0 / 348 | not stated; safety; registry:adverse_events | ||||
| A3 | events | 0 / 347 | not stated; safety; registry:adverse_events | ||||
| A4 | events | 0 / 348 | not stated; safety; registry:adverse_events |