parallel randomized trial
DUAL™ I
A 26 Week Randomised, Parallel Three-arm, Open-label, Multi-centre, Multinational Treat-to-target Trial Comparing Fixed Ratio Combination of Insulin Degludec and Liraglutide Versus Insulin Degludec or Liraglutide Alone, in Subjects With Type 2 Diabetes Treated With 1-2 Oral Anti-diabetic Drugs (OADs)With a 26 Week Extension
Design
Conduct and analysis
Arms
| Arm | Treatment | Background | Randomized | Analyzed | Completed treatment |
|---|---|---|---|---|---|
| A1 | Insulin degludec and liraglutide (IDegLira) subcutaneous once daily titrated IDegLira | metformin with or without pioglitazone; lifestyle: not reported | 834 | 833 | |
| A2 | Insulin degludec Insulin degludec | metformin with or without pioglitazone; lifestyle: not reported | 414 | 413 | |
| A3 | Liraglutide 1.8 mg subcutaneous once daily Liraglutide | metformin with or without pioglitazone; lifestyle: not reported | 415 | 414 |
Baseline characteristics
As printed in the trial reports or registry, per arm or for the whole trial.
| Characteristic | Statistic | Insulin degludec and liraglutide (IDegLira) subcutaneous once daily titrated A1 | Insulin degludec A2 | Liraglutide 1.8 mg subcutaneous once daily A3 |
|---|---|---|---|---|
| age | mean (years) | 55.1 | 54.9 | 55.0 |
| age | sd (years) | 9.9 | 9.7 | 10.2 |
| asian | percent | 27.3 | 29.1 | 28.1 |
| black | percent | 8.6 | 5.6 | 6.8 |
| bmi | mean (kg/m2) | 31.2 | 31.2 | 31.3 |
| bmi | sd (kg/m2) | 5.2 | 5.3 | 4.8 |
| diabetes duration | mean (years) | 6.6 | 7.0 | 7.2 |
| diabetes duration | sd (years) | 5.1 | 5.3 | 6.1 |
| female | n | 398 | 213 | 206 |
| female | percent | 47.8 | 51.6 | 49.8 |
| hba1c | mean (percent) | 8.3 | 8.3 | 8.3 |
| hba1c | sd (percent) | 0.9 | 1.0 | 0.9 |
| other background: metformin and pioglitazone | n | 142 | 70 | 75 |
| other background: metformin and pioglitazone | percent | 17.0 | 16.9 | 18.1 |
| other background: metformin only | n | 691 | 343 | 338 |
| other background: metformin only | percent | 83.0 | 83.1 | 81.6 |
| other race other | percent | 2.4 | 3.2 | 2.9 |
| weight | mean (kg) | 87.2 | 87.4 | 87.4 |
| weight | sd (kg) | 19.0 | 19.2 | 18.0 |
| white | percent | 61.6 | 62.2 | 62.3 |
Results
157 adjudicated result lines, grouped by outcome. Open an outcome to see its values.
HbA1c change (55 lines; O01)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 vs A3 | md | -0.64 percent | -0.75 to -0.53 | not stated; full analysis; registry:outcomes | ||
| 26 | A1 | change | -1.91 percent | 1.07 | 833 | not stated; full analysis; registry:outcomes | |
| 26 | A1 vs A2 | md | -0.47 percent | -0.58 to -0.36 | not stated; full analysis; registry:outcomes | ||
| 26 | A2 | change | -1.44 percent | 1.03 | 413 | not stated; full analysis; registry:outcomes | |
| 26 | A3 | change | -1.28 percent | 1.13 | 414 | not stated; full analysis; registry:outcomes | |
| 52 | A1 vs A2 | md | -0.46 percent | -0.57 to -0.34 | not stated; full analysis; R0021244:Results | ||
| 52 | A1 | final | 6.0 percent | 208 | not stated; full analysis; hba1c:7.5_or_less; R0013496:Figure 1 | ||
| 52 | A1 | change | -1.9 percent | 99 | not stated; full analysis; bmi:less_than_25; R0021244:Figure 2 | ||
| 52 | A1 vs A2 | md | -0.45 percent | -0.56 to -0.34 | not stated; completers; R0021244:Supplement Table S3 | ||
| 52 | A1 vs A2 | md | -0.46 percent | -0.58 to -0.35 | not stated; full analysis; R0021244:Supplement Table S3 | ||
| 52 | A1 vs A2 | md | -0.45 percent | -0.56 to -0.33 | not stated; per protocol; R0021244:Supplement Table S3 | ||
| 52 | A1 vs A3 | md | -0.65 percent | -0.76 to -0.53 | not stated; full analysis; R0021244:Results | ||
| 52 | A1 vs A3 | md | -0.56 percent | -0.68 to -0.45 | not stated; completers; R0021244:Supplement Table S3 | ||
| 52 | A1 vs A3 | md | -0.63 percent | -0.75 to -0.51 | not stated; full analysis; R0021244:Supplement Table S3 | ||
| 52 | A1 vs A3 | md | -0.66 percent | -0.77 to -0.54 | not stated; per protocol; R0021244:Supplement Table S3 | ||
| 52 | A1 vs A3 | md | -0.77 percent | -1.08 to -0.46 | not stated; full analysis; region:india; R0017641:Results | ||
| 52 | A1 vs A2 | md | -0.91 percent | -1.21 to -0.61 | not stated; full analysis; region:india; R0017641:Results | ||
| 52 | A1 | change | -2.1 percent | 1.1 | 140 | not stated; full analysis; background:metformin_and_pioglitazone; R0013496:Table 1 | |
| 52 | A1 vs A2 | md | -0.59 percent | -0.87 to -0.31 | not stated; full analysis; background:metformin_and_pioglitazone; R0013496:Table 1 | ||
| 52 | A1 vs A3 | md | -0.81 percent | -1.08 to -0.53 | not stated; full analysis; background:metformin_and_pioglitazone; R0013496:Table 1 | ||
| 52 | A1 | final | 7.0 percent | 190 | not stated; full analysis; hba1c:more_than_9.0; R0013496:Figure 1 | ||
| 52 | A1 | change | -1.8 percent | 1.1 | 693 | not stated; full analysis; background:metformin_only; R0013496:Table 1 | |
| 52 | A1 vs A2 | md | -0.43 percent | -0.56 to -0.30 | not stated; full analysis; background:metformin_only; R0013496:Table 1 | ||
| 52 | A1 vs A3 | md | -0.60 percent | -0.73 to -0.47 | not stated; full analysis; background:metformin_only; R0013496:Table 1 | ||
| 52 | A1 | change | -1.8 percent | 257 | not stated; full analysis; bmi:25_to_less_than_30; R0021244:Figure 2 | ||
| 52 | A1 | final | 6.6 percent | 136 | not stated; full analysis; hba1c:more_than_8.5_to_9.0; R0013496:Figure 1 | ||
| 52 | A1 | change | -1.84 percent | 833 | not stated; full analysis; R0021244:Results | ||
| 52 | A1 | change | -1.9 percent | 258 | not stated; full analysis; bmi:30_to_less_than_35; R0021244:Figure 2 | ||
| 52 | A1 | final | 6.4 percent | 833 | not stated; full analysis; R0021244:Figure 1 | ||
| 52 | A1 | final | 6.2 percent | 299 | not stated; full analysis; hba1c:more_than_7.5_to_8.5; R0013496:Figure 1 | ||
| 52 | A1 | change | -1.8 percent | 219 | not stated; full analysis; bmi:35_or_more; R0021244:Figure 2 | ||
| 52 | A2 | final | 7.2 percent | 59 | not stated; full analysis; hba1c:more_than_8.5_to_9.0; R0013496:Figure 1 | ||
| 52 | A2 | change | -1.40 percent | 413 | not stated; full analysis; R0021244:Results | ||
| 52 | A2 | final | 6.9 percent | 413 | not stated; full analysis; R0021244:Figure 1 | ||
| 52 | A2 | change | -1.6 percent | 1.0 | 69 | not stated; full analysis; background:metformin_and_pioglitazone; R0013496:Table 1 | |
| 52 | A2 | change | -1.4 percent | 1.1 | 344 | not stated; full analysis; background:metformin_only; R0013496:Table 1 | |
| 52 | A2 | change | -1.5 percent | 119 | not stated; full analysis; bmi:25_to_less_than_30; R0021244:Figure 2 | ||
| 52 | A2 | change | -1.5 percent | 123 | not stated; full analysis; bmi:30_to_less_than_35; R0021244:Figure 2 | ||
| 52 | A2 | change | -1.4 percent | 116 | not stated; full analysis; bmi:35_or_more; R0021244:Figure 2 | ||
| 52 | A2 | change | -1.1 percent | 55 | not stated; full analysis; bmi:less_than_25; R0021244:Figure 2 | ||
| 52 | A2 | final | 6.4 percent | 124 | not stated; full analysis; hba1c:7.5_or_less; R0013496:Figure 1 | ||
| 52 | A2 | final | 6.7 percent | 123 | not stated; full analysis; hba1c:more_than_7.5_to_8.5; R0013496:Figure 1 | ||
| 52 | A2 | final | 7.6 percent | 107 | not stated; full analysis; hba1c:more_than_9.0; R0013496:Figure 1 | ||
| 52 | A3 | change | -1.1 percent | 136 | not stated; full analysis; bmi:30_to_less_than_35; R0021244:Figure 2 | ||
| 52 | A3 | change | -1.3 percent | 111 | not stated; full analysis; bmi:35_or_more; R0021244:Figure 2 | ||
| 52 | A3 | final | 6.4 percent | 117 | not stated; full analysis; hba1c:7.5_or_less; R0013496:Figure 1 | ||
| 52 | A3 | final | 7.1 percent | 139 | not stated; full analysis; hba1c:more_than_7.5_to_8.5; R0013496:Figure 1 | ||
| 52 | A3 | change | -1.3 percent | 120 | not stated; full analysis; bmi:25_to_less_than_30; R0021244:Figure 2 | ||
| 52 | A3 | change | -1.2 percent | 1.2 | 341 | not stated; full analysis; background:metformin_only; R0013496:Table 1 | |
| 52 | A3 | final | 7.3 percent | 72 | not stated; full analysis; hba1c:more_than_8.5_to_9.0; R0013496:Figure 1 | ||
| 52 | A3 | change | -1.3 percent | 1.2 | 73 | not stated; full analysis; background:metformin_and_pioglitazone; R0013496:Table 1 | |
| 52 | A3 | change | -1.1 percent | 47 | not stated; full analysis; bmi:less_than_25; R0021244:Figure 2 | ||
| 52 | A3 | final | 7.7 percent | 86 | not stated; full analysis; hba1c:more_than_9.0; R0013496:Figure 1 | ||
| 52 | A3 | final | 7.1 percent | 414 | not stated; full analysis; R0021244:Figure 1 | ||
| 52 | A3 | change | -1.21 percent | 414 | not stated; full analysis; R0021244:Results |
Body weight change in kilograms (diabetes) (13 lines; O02)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | change | -0.5 kg | 3.5 | 833 | not stated; full analysis; registry:outcomes | |
| 26 | A2 | change | 1.6 kg | 4.0 | 413 | not stated; full analysis; registry:outcomes | |
| 26 | A3 | change | -3.0 kg | 3.5 | 414 | not stated; full analysis; registry:outcomes | |
| 52 | A1 vs A3 | md | 2.66 kg | not stated; full analysis; R0021244:Figure 1 | |||
| 52 | A1 | change | -0.4 kg | 833 | not stated; full analysis; R0021244:Results | ||
| 52 | A1 vs A2 | md | -2.80 kg | not stated; full analysis; R0021244:Figure 1 | |||
| 52 | A1 | change | -0.3 kg | 125 | not stated; full analysis; region:india; R0017641:Results | ||
| 52 | A1 vs A2 | md | -1.61 kg | -2.45 to -0.78 | not stated; full analysis; region:india; R0017641:Results | ||
| 52 | A1 vs A3 | md | 1.72 kg | 0.87 to 2.58 | not stated; full analysis; region:india; R0017641:Results | ||
| 52 | A2 | change | 1.8 kg | 65 | not stated; full analysis; region:india; R0017641:Results | ||
| 52 | A2 | change | 2.3 kg | 413 | not stated; full analysis; R0021244:Results | ||
| 52 | A3 | change | -3.0 kg | 414 | not stated; full analysis; R0021244:Results | ||
| 52 | A3 | change | -2.3 kg | 61 | not stated; full analysis; region:india; R0017641:Results |
HbA1c below 7 percent (6 lines; O03)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 26 | A1 | responders | 80.6 | 833 | not stated; full analysis; R0021244:Figure 2 | ||
| 26 | A2 | responders | 65.1 | 413 | not stated; full analysis; R0021244:Figure 2 | ||
| 26 | A3 | responders | 60.4 | 414 | not stated; full analysis; R0021244:Figure 2 | ||
| 52 | A1 | responders | 78.2 | 833 | not stated; full analysis; R0021244:Figure 2 | ||
| 52 | A2 | responders | 62.5 | 413 | not stated; full analysis; R0021244:Figure 2 | ||
| 52 | A3 | responders | 56.5 | 414 | not stated; full analysis; R0021244:Figure 2 |
Level 2 or 3 hypoglycemia (participants) (6 lines; O04)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 825 | while on treatment; safety; registry:adverse_events | ||||
| A1 | events | 1 / 825 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 0 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 0 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 0 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 0 / 412 | while on treatment; safety; registry:adverse_events |
Level 2 or 3 hypoglycemia (episode rate) (15 lines; O04B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 vs A3 | rate ratio | 11.71 | 8.47 to 16.17 | not stated; full analysis; R0015570:Figure 1B | |||
| A1 | rate | 176.7 | not stated; safety; R0021244:Results | ||||
| A1 | rate | 4.20 | not stated; safety; R0015570:Table 2 | ||||
| A1 vs A2 | rate ratio | 0.59 | 0.46 to 0.77 | not stated; full analysis; R0015570:Figure 1A | |||
| A1 vs A2 | rate ratio | 0.63 | 0.50 to 0.79 | not stated; full analysis; R0021244:Results | |||
| A1 vs A2 | rate ratio | 0.68 | 0.44 to 1.06 | not stated; full analysis; R0021244:Results | |||
| A1 vs A3 | rate ratio | 8.52 | 6.09 to 11.93 | not stated; full analysis; R0021244:Results | |||
| A1 vs A3 | rate ratio | 11.99 | 4.85 to 29.63 | not stated; full analysis; R0021244:Results | |||
| A1 | rate | 22.3 | not stated; safety; R0021244:Results | ||||
| A2 | rate | 6.40 | not stated; safety; R0015570:Table 2 | ||||
| A2 | rate | 279.1 | not stated; safety; R0021244:Results | ||||
| A2 | rate | 36.6 | not stated; safety; R0021244:Results | ||||
| A3 | rate | 1.8 | not stated; safety; R0021244:Results | ||||
| A3 | rate | 19.1 | not stated; safety; R0021244:Results | ||||
| A3 | rate | 0.37 | not stated; safety; R0015570:Table 2 |
Systolic blood pressure change (1 lines; O05)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| 52 | A1 vs A2 | md | -1.54 mmHg | -2.89 to -0.19 | not stated; other; R0021244:Results |
Acute kidney injury (3 lines; O121)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 825 | while on treatment; safety; renal failure acute; registry:adverse_events | ||||
| A2 | events | 1 / 412 | while on treatment; safety; renal failure acute; registry:adverse_events | ||||
| A3 | events | 0 / 412 | while on treatment; safety; renal failure acute; registry:adverse_events |
Three point MACE (2 lines; O21)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A2 | events | 1 / | not stated; other; R0021244:Results | ||||
| A3 | events | 1 / | not stated; other; R0021244:Results |
Hospitalization for heart failure (3 lines; O23)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / | not stated; other; R0021244:Results | ||||
| A2 | events | 1 / | not stated; other; R0021244:Results | ||||
| A3 | events | 0 / | not stated; other; R0021244:Results |
Serious adverse events (6 lines; O25)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 38 / 825 | while on treatment; safety; registry:adverse_events | ||||
| A1 | events | 4.6 | 825 | not stated; safety; R0021244:Table 2 | |||
| A2 | events | 5.3 | 412 | not stated; safety; R0021244:Table 2 | |||
| A2 | events | 22 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 24 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 5.8 | 412 | not stated; safety; R0021244:Table 2 |
Discontinuation due to adverse events (6 lines; O26)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 14 / 825 | not stated; safety; R0021244:Results | ||||
| A1 | events | 5 / 833 | not stated; randomized; R0021244:Figure S1 | ||||
| A2 | events | 1 / 414 | not stated; randomized; R0021244:Figure S1 | ||||
| A2 | events | 9 / 412 | not stated; safety; R0021244:Results | ||||
| A3 | events | 26 / 412 | not stated; safety; R0021244:Results | ||||
| A3 | events | 2 / 415 | not stated; randomized; R0021244:Figure S1 |
Nausea (3 lines; O27A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 85 / 825 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 16 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 92 / 412 | while on treatment; safety; registry:adverse_events |
Vomiting (6 lines; O27B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 41 / 825 | while on treatment; safety; registry:adverse_events | ||||
| A1 | events | 0 / 825 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 0 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 10 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 37 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 1 / 412 | while on treatment; safety; registry:adverse_events |
Diarrhea (3 lines; O27C)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 84 / 825 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 28 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 67 / 412 | while on treatment; safety; registry:adverse_events |
Constipation (3 lines; O27D)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 26 / 825 | while on treatment; safety; registry:adverse_events | ||||
| A2 | events | 4 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 21 / 412 | while on treatment; safety; registry:adverse_events |
Gallbladder and biliary disease (9 lines; O28)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 2 / 825 | while on treatment; safety; biliary colic; registry:adverse_events | ||||
| A1 | events | 0 / 825 | while on treatment; safety; cholecystitis; registry:adverse_events | ||||
| A1 | events | 0 / 825 | while on treatment; safety; cholelithiasis; registry:adverse_events | ||||
| A2 | events | 2 / 412 | while on treatment; safety; cholelithiasis; registry:adverse_events | ||||
| A2 | events | 0 / 412 | while on treatment; safety; biliary colic; registry:adverse_events | ||||
| A2 | events | 1 / 412 | while on treatment; safety; cholecystitis; registry:adverse_events | ||||
| A3 | events | 0 / 412 | while on treatment; safety; biliary colic; registry:adverse_events | ||||
| A3 | events | 0 / 412 | while on treatment; safety; cholecystitis; registry:adverse_events | ||||
| A3 | events | 1 / 412 | while on treatment; safety; cholelithiasis; registry:adverse_events |
Acute pancreatitis (5 lines; O29)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 825 | while on treatment; safety; registry:adverse_events | ||||
| A1 | events | 0 / | not stated; other; R0021244:Results | ||||
| A2 | events | 0 / | not stated; other; R0021244:Results | ||||
| A2 | events | 0 / 412 | while on treatment; safety; registry:adverse_events | ||||
| A3 | events | 0 / 412 | while on treatment; safety; registry:adverse_events |
Medullary thyroid carcinoma (3 lines; O32A)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / | not stated; other; R0021244:Results | ||||
| A2 | events | 0 / | not stated; other; R0021244:Results | ||||
| A3 | events | 0 / | not stated; other; R0021244:Results |
Thyroid cancer (any) (3 lines; O32B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / | not stated; other; R0021244:Results | ||||
| A2 | events | 0 / | not stated; other; R0021244:Results | ||||
| A3 | events | 0 / | not stated; other; R0021244:Results |
Intestinal obstruction or ileus (3 lines; O37B)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 1 / 825 | while on treatment; safety; small intestinal obstruction; registry:adverse_events | ||||
| A2 | events | 0 / 412 | while on treatment; safety; small intestinal obstruction; registry:adverse_events | ||||
| A3 | events | 0 / 412 | while on treatment; safety; small intestinal obstruction; registry:adverse_events |
Pancreatic cancer (3 lines; O38)
| Week | Arm | Statistic | Estimate | SE or SD | 95% CI | Events / N | Detail |
|---|---|---|---|---|---|---|---|
| A1 | events | 0 / 825 | while on treatment; safety; pancreatic carcinoma stage iv; registry:adverse_events | ||||
| A2 | events | 0 / 412 | while on treatment; safety; pancreatic carcinoma stage iv; registry:adverse_events | ||||
| A3 | events | 1 / 412 | while on treatment; safety; pancreatic carcinoma stage iv; registry:adverse_events |