parallel randomized trial
NCT01272219
Effect of Liraglutide on Body Weight in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities: A Randomised, Double-blind, Placebo Controlled, Parallel Group, Multi-centre, Multinational Trial With Stratification of Subject to Either 56 or 160 Weeks of Treatment Based on Pre-diabetes Status at Randomisation
Overweight or obesity without diabetes (adults)Weight maintenance after a GLP-1 receptor agonist containing run inNCT01272219S000492
Design
Conduct and analysis
Arms
| Arm | Treatment | Background | Randomized | Analyzed | Completed treatment |
|---|---|---|---|---|---|
| A1 | Liraglutide 3.0 mg subcutaneous once daily Liraglutide 3.0 mg | lifestyle: standard | 2,487 | 2,432 | |
| A2 | Placebo Placebo | lifestyle: standard | 1,244 | 1,220 | |
| A3 | Liraglutide 3.0 mg subcutaneous once daily Liraglutide then liraglutide (weeks 56 to 68) | lifestyle: standard | 351 | 349 | |
| A4 | Placebo Liraglutide then placebo (weeks 56 to 68) | lifestyle: standard | 350 | 346 |
Baseline characteristics
As printed in the trial reports or registry, per arm or for the whole trial.
| Characteristic | Statistic | Liraglutide 3.0 mg subcutaneous once daily A1 | Placebo A2 | Liraglutide 3.0 mg subcutaneous once daily A3 | Placebo A4 |
|---|---|---|---|---|---|
| age: 18 to 39 | n | 856 | 415 | ||
| age: 18 to 39 | percent | 34.4 | 33.4 | ||
| age: 40 to 64 | n | 1495 | 760 | ||
| age: 40 to 64 | percent | 60.1 | 61.1 | ||
| age: 65 to 74 | n | 130 | 68 | ||
| age: 65 to 74 | percent | 5.2 | 5.5 | ||
| age: 75 or more | n | 6 | 1 | ||
| age: 75 or more | percent | 0.2 | |||
| age | mean (years) | 45.2 | 45.0 | ||
| age | sd (years) | 12.1 | 12.0 | ||
| asian | percent | 3.6 | 3.7 | ||
| bmi: 27.0 to 29.9 | n | 66 | 44 | ||
| bmi: 27.0 to 29.9 | percent | 2.7 | 3.5 | ||
| bmi: 30.0 to 34.9 | n | 806 | 388 | ||
| bmi: 30.0 to 34.9 | percent | 32.4 | 31.2 | ||
| bmi: 35.0 to 39.9 | n | 787 | 398 | ||
| bmi: 35.0 to 39.9 | percent | 31.6 | 32.0 | ||
| bmi: more than 40 | n | 828 | 414 | ||
| bmi: more than 40 | percent | 33.3 | 33.3 | ||
| bmi | mean (kg/m2) | 38.3 | 38.3 | ||
| bmi | sd (kg/m2) | 6.4 | 6.3 | ||
| established cvd | n | 216 | 105 | ||
| established cvd | percent | 8.7 | 8.5 | ||
| female | n | 1957 | 971 | ||
| female | percent | 78.7 | 78.1 | ||
| hba1c | mean (percent) | 5.6 | 5.6 | ||
| hba1c | sd (percent) | 0.4 | 0.4 | ||
| sbp | mean (mmHg) | 123.0 | 123.2 | ||
| sbp | sd (mmHg) | 12.9 | 12.8 | ||
| waist | mean (cm) | 115.0 | 114.5 | ||
| waist | sd (cm) | 14.4 | 14.3 | ||
| weight | mean (kg) | 106.2 | 106.2 | ||
| weight | sd (kg) | 21.2 | 21.7 |
Analyses this trial contributes to
- Percent body weight changeOverweight or obesity without diabetes (adults); weeks 40 to 104 (target week 68); network meta-analysis
- Percent body weight changeOverweight or obesity without diabetes (adults); weeks 40 to 104 (target week 68); network meta-analysis
- Three point MACEOverweight or obesity without diabetes (adults); longest follow-up; descriptive only
- Three point MACEOverweight or obesity without diabetes (adults); longest follow-up; descriptive only
- SF-36 physical component summary changeOverweight or obesity without diabetes (adults); weeks 20 to 130 (target week 52); network meta-analysis
- SF-36 physical component summary changeOverweight or obesity without diabetes (adults); weeks 20 to 130 (target week 52); network meta-analysis
- Serious adverse eventsOverweight or obesity without diabetes (adults); longest follow-up; network meta-analysis
- Serious adverse eventsOverweight or obesity without diabetes (adults); longest follow-up; network meta-analysis
Results
107 adjudicated result lines, grouped by outcome. Open an outcome to see its values.
Percent body weight change (5 lines; O10)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 56 | A1 vs A2 | md | -5.39 percent | -5.82 to -4.95 | not stated; full analysis; registry:outcomes | ||
| 56 | A1 | percent change | -7.98 percent | 6.67 | 2432 | not stated; full analysis; registry:outcomes | |
| 56 | A2 | percent change | -2.62 percent | 5.74 | 1220 | not stated; full analysis; registry:outcomes | |
| 160 | A1 | percent change | -6.14 percent | 7.34 | 1467 | not stated; full analysis; prediabetes:yes; registry:outcomes | |
| 160 | A2 | percent change | -1.89 percent | 6.27 | 734 | not stated; full analysis; prediabetes:yes; registry:outcomes |
Weight loss of 5 percent or more (5 lines; O11A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 56 | A1 | responders | 63.2 | 2432 | not stated; full analysis; registry:outcomes | ||
| 56 | A1 vs A2 | or | 4.80 | 4.12 to 5.60 | not stated; full analysis; registry:outcomes | ||
| 56 | A2 | responders | 27.1 | 1220 | not stated; full analysis; registry:outcomes | ||
| 160 | A1 | responders | 49.6 | 1467 | not stated; full analysis; prediabetes:yes; registry:outcomes | ||
| 160 | A2 | responders | 23.7 | 734 | not stated; full analysis; prediabetes:yes; registry:outcomes |
Weight loss of 10 percent or more (5 lines; O11B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 56 | A1 | responders | 33.1 | 2432 | not stated; full analysis; registry:outcomes | ||
| 56 | A1 vs A2 | or | 4.34 | 3.54 to 5.32 | not stated; full analysis; registry:outcomes | ||
| 56 | A2 | responders | 10.6 | 1220 | not stated; full analysis; registry:outcomes | ||
| 160 | A1 | responders | 24.8 | 1467 | not stated; full analysis; prediabetes:yes; registry:outcomes | ||
| 160 | A2 | responders | 9.9 | 734 | not stated; full analysis; prediabetes:yes; registry:outcomes |
Weight loss of 15 percent or more (2 lines; O11C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 160 | A1 | responders | 10.9 | 161 / | not stated; other; prediabetes:yes; R0025539:Results | ||
| 160 | A2 | responders | 3.1 | 23 / | not stated; other; prediabetes:yes; R0025539:Results |
Percent body weight change after randomization in maintenance trials (2 lines; O12)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 12 | A3 | percent change | 0.69 percent | 2.58 | 349 | not stated; full analysis; period:second_randomization; registry:outcomes | |
| 12 | A4 | percent change | 2.91 percent | 3.01 | 346 | not stated; full analysis; period:second_randomization; registry:outcomes |
Acute kidney injury (2 lines; O121)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 2 / 1524 | not stated; safety; prediabetes:yes; renal failure acute; registry:adverse_events | ||||
| A2 | events | 2 / 755 | not stated; safety; prediabetes:yes; renal failure acute; registry:adverse_events |
Progression to type 2 diabetes (4 lines; O14)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0.2 | 2437 | not stated; full analysis; registry:outcomes | |||
| A1 | events | 26 / 1472 | not stated; full analysis; prediabetes:yes; registry:outcomes | ||||
| A2 | events | 1.1 | 1225 | not stated; full analysis; registry:outcomes | |||
| A2 | events | 46 / 738 | not stated; full analysis; prediabetes:yes; registry:outcomes |
All cause mortality (2 lines; O20)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 2481 | not stated; safety; R0026209:Table 6 | ||||
| A2 | events | 2 / 1242 | not stated; safety; R0026209:Table 6 |
Three point MACE (3 lines; O21)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 6 / | while on treatment; other; R0013170:Table 1 | ||||
| A1 vs A2 | hr | 0.70 | 0.20 to 2.50 | while on treatment; other; R0013170:Table 1 | |||
| A2 | events | 4 / | while on treatment; other; R0013170:Table 1 |
SF-36 physical component summary change (7 lines; O24A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 56 | A1 | change | 3.66 points | 0.15 | 1690 | not stated; full analysis; R0026099:Table 2 | |
| 56 | A1 vs A2 | md | 1.73 points | 1.22 to 2.24 | not stated; full analysis; R0026099:Results | ||
| 56 | A1 vs A2 | md | 1.78 points | 1.24 to 2.33 | not stated; full analysis; R0026099:Results | ||
| 56 | A2 | change | 1.93 points | 0.21 | 799 | not stated; full analysis; R0026099:Table 2 | |
| 160 | A1 | change | 3.1 points | 7.3 | 993 | not stated; full analysis; prediabetes:yes; R0025539:Results | |
| 160 | A1 vs A2 | md | 0.87 points | 0.17 to 1.58 | not stated; full analysis; prediabetes:yes; R0025539:Results | ||
| 160 | A2 | change | 2.6 points | 7.6 | 469 | not stated; full analysis; prediabetes:yes; R0025539:Results |
Physical functioning (any instrument) (7 lines; O24B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 56 | A1 | change | 13.36 points | 0.31 | 1891 | not stated; full analysis; R0026099:Table 2 | |
| 56 | A1 | change | 3.64 points | 0.15 | 1689 | not stated; full analysis; R0026099:Table 2 | |
| 56 | A1 vs A2 | md | 4.80 points | 3.72 to 5.89 | not stated; full analysis; R0026099:Results | ||
| 56 | A2 | change | 8.55 points | 0.46 | 891 | not stated; full analysis; R0026099:Table 2 | |
| 56 | A2 | change | 2.08 points | 0.22 | 799 | not stated; full analysis; R0026099:Table 2 | |
| 160 | A1 vs A2 | md | 4.5 points | 2.9 to 6.1 | not stated; full analysis; prediabetes:yes; R0025539:Results | ||
| 160 | A1 vs A2 | md | 1.47 points | 0.78 to 2.16 | not stated; full analysis; prediabetes:yes; R0025539:Results |
Health related quality of life total score (any instrument) (7 lines; O24C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 56 | A1 | change | 10.66 points | 0.25 | 1891 | not stated; full analysis; R0026099:Table 2 | |
| 56 | A1 vs A2 | md | 3.13 points | 2.24 to 4.01 | not stated; full analysis; R0026099:Results | ||
| 56 | A1 vs A2 | md | 3.48 points | 2.52 to 4.45 | not stated; full analysis; R0026099:Results | ||
| 56 | A2 | change | 7.54 points | 0.37 | 890 | not stated; full analysis; R0026099:Table 2 | |
| 160 | A1 | change | 10.96 points | 1117 | not stated; full analysis; prediabetes:yes; R0025539:Table 2 | ||
| 160 | A1 vs A2 | md | 3.35 points | 2.04 to 4.66 | not stated; full analysis; prediabetes:yes; R0025539:Results | ||
| 160 | A2 | change | 8.11 points | 517 | not stated; full analysis; prediabetes:yes; R0025539:Table 2 |
Serious adverse events (4 lines; O25)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 230 / 1524 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A1 | events | 154 / 2481 | not stated; safety; R0026209:Table 6 | ||||
| A2 | events | 96 / 755 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A2 | events | 62 / 1242 | not stated; safety; R0026209:Table 6 |
Discontinuation due to adverse events (10 lines; O26)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 86 / 959 | not stated; randomized; prediabetes:no; registry:flow | ||||
| A1 | events | 244 / 2481 | not stated; safety; R0026209:Table 6 | ||||
| A1 | events | 191 / 1505 | not stated; randomized; prediabetes:yes; registry:flow | ||||
| A1 | events | 152 / 1528 | not stated; randomized; prediabetes:yes; registry:flow | ||||
| A2 | events | 47 / 1242 | not stated; safety; R0026209:Table 6 | ||||
| A2 | events | 16 / 487 | not stated; randomized; prediabetes:no; registry:flow | ||||
| A2 | events | 29 / 757 | not stated; randomized; prediabetes:yes; registry:flow | ||||
| A2 | events | 43 / 749 | not stated; randomized; prediabetes:yes; registry:flow | ||||
| A3 | events | 1 / 351 | not stated; randomized; period:second_randomization; registry:flow | ||||
| A4 | events | 1 / 350 | not stated; randomized; period:second_randomization; registry:flow |
Nausea (4 lines; O27A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 1524 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A1 | events | 622 / 1524 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A2 | events | 128 / 755 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; registry:adverse_events |
Vomiting (4 lines; O27B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 300 / 1524 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A1 | events | 1 / 1524 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A2 | events | 42 / 755 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; registry:adverse_events |
Diarrhea (4 lines; O27C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 388 / 1524 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A1 | events | 0 / 1524 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A2 | events | 107 / 755 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A2 | events | 2 / 755 | not stated; safety; prediabetes:yes; registry:adverse_events |
Constipation (4 lines; O27D)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 333 / 1524 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A1 | events | 0 / 1524 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A2 | events | 85 / 755 | not stated; safety; prediabetes:yes; registry:adverse_events |
Gallbladder and biliary disease (12 lines; O28)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 2 / 1524 | not stated; safety; prediabetes:yes; biliary colic; registry:adverse_events | ||||
| A1 | events | 3 / 1524 | not stated; safety; prediabetes:yes; bile duct stone; registry:adverse_events | ||||
| A1 | events | 9 / 1524 | not stated; safety; prediabetes:yes; cholecystitis acute; registry:adverse_events | ||||
| A1 | events | 1 / 1524 | not stated; safety; prediabetes:yes; cholecystitis chronic; registry:adverse_events | ||||
| A1 | events | 6 / 1524 | not stated; safety; prediabetes:yes; cholecystitis; registry:adverse_events | ||||
| A1 | events | 22 / 1524 | not stated; safety; prediabetes:yes; cholelithiasis; registry:adverse_events | ||||
| A2 | events | 6 / 755 | not stated; safety; prediabetes:yes; cholelithiasis; registry:adverse_events | ||||
| A2 | events | 1 / 755 | not stated; safety; prediabetes:yes; cholecystitis acute; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; bile duct stone; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; biliary colic; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; cholecystitis chronic; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; cholecystitis; registry:adverse_events |
Acute pancreatitis (4 lines; O29)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 2 / 1524 | not stated; safety; prediabetes:yes; Pancreatitis; registry:adverse_events | ||||
| A1 | events | 3 / 1524 | not stated; safety; prediabetes:yes; Pancreatitis acute; registry:adverse_events | ||||
| A2 | events | 1 / 755 | not stated; safety; prediabetes:yes; Pancreatitis acute; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; Pancreatitis; registry:adverse_events |
Thyroid cancer (any) (2 lines; O32B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 2 / 1524 | not stated; safety; prediabetes:yes; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; registry:adverse_events |
Suicidal ideation or behavior (4 lines; O35A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 1524 | not stated; safety; prediabetes:yes; suicidal ideation; registry:adverse_events | ||||
| A1 | events | 1 / 1524 | not stated; safety; prediabetes:yes; suicide attempt; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; suicidal ideation; registry:adverse_events | ||||
| A2 | events | 1 / 755 | not stated; safety; prediabetes:yes; suicide attempt; registry:adverse_events |
Intestinal obstruction or ileus (2 lines; O37B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 1524 | not stated; safety; prediabetes:yes; intestinal obstruction; registry:adverse_events | ||||
| A2 | events | 0 / 755 | not stated; safety; prediabetes:yes; intestinal obstruction; registry:adverse_events |
Pancreatic cancer (2 lines; O38)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 1524 | not stated; safety; prediabetes:yes; pancreatic carcinoma metastatic; registry:adverse_events | ||||
| A2 | events | 1 / 755 | not stated; safety; prediabetes:yes; pancreatic carcinoma metastatic; registry:adverse_events |