parallel randomized trial

DUAL™ I Japan

A Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide, Insulin Degludec and Liraglutide in Japanese Subjects With Type 2 Diabetes Mellitus

Type 2 diabetes (adults)NCT02607306S001965

Design

Randomized: 819
Start year: 2015
Treatment: 52 weeks, follow-up 53 weeks
Countries: Japan
Sponsor: Novo Nordisk A/S (industry)
Eligibility: Japanese adults 20 or older; HbA1c 7.0 to 11.0 percent; BMI at least 20; insulin naive on one oral drug

Conduct and analysis

Blinding: open label
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: full analysis
Missing data: LOCF

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Insulin degludec and liraglutide (IDegLira) subcutaneous once daily titrated IDegLira	pretrial oral antidiabetic drug; lifestyle: not reported	275	275
A2	Insulin degludec Insulin degludec	pretrial oral antidiabetic drug; lifestyle: not reported	271	271
A3	Liraglutide 1.8 mg subcutaneous once daily Liraglutide 1.8 mg	pretrial oral antidiabetic drug; lifestyle: not reported	273	273

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)	56.9	57.8	56.8
age	median (years)	57.0	59.0	57.0
age	sd (years)	10.2	9.9	10.1
bmi	mean (kg/m2)	26.1	26.6	26.5
bmi	sd (kg/m2)	3.7	4.8	4.5
diabetes duration	mean (years)	9.2	9.7	9.4
diabetes duration	sd (years)	6.2	6.0	5.9
female	n	81	76	81
female	percent	29.5	28.0	29.7
hba1c	mean (percent)	8.5	8.5	8.3
hba1c	sd (percent)	1.1	1.1	1.0
other background: agi only	n	41	40	41
other background: agi only	percent	14.9	14.8	15.0
other background: glinide only	n	40	39	40
other background: glinide only	percent	14.5	14.4	14.7
other background: metformin only	n	47	46	47
other background: metformin only	percent	17.1	17.0	17.2
other background: sglt2i only	n	61	61	61
other background: sglt2i only	percent	22.2	22.5	22.3
other background: sulfonylurea only	n	43	42	42
other background: sulfonylurea only	percent	15.6	15.5	15.4
other background: tzd only	n	43	43	42
other background: tzd only	percent	15.6	15.9	15.4
weight	mean (kg)	70.7	72.6	72.2
weight	sd (kg)	12.4	14.5	15.0

Analyses this trial contributes to

Results

160 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

HbA1c change (45 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-2.50 percent	1.03		197	not stated; other; age:less_than_65; R0013892:Supplement Table S1
52	A1 vs A3	md	-0.48 percent		-0.60 to -0.37		not stated; full analysis; R0014857:Results
52	A1	change	-2.43 percent	1.12		112	not stated; other; bmi:25_to_less_than_30; R0013892:Supplement Table S1
52	A1 vs A2	md	-0.71 percent		-0.89 to -0.52		not stated; other; bmi:25_to_less_than_30; R0013892:Supplement Table S1
52	A1 vs A3	md	-0.44 percent		-0.62 to -0.26		not stated; other; bmi:25_to_less_than_30; R0013892:Supplement Table S1
52	A1	change	-2.47 percent	0.95		41	not stated; other; bmi:30_or_more; R0013892:Supplement Table S1
52	A1 vs A2	md	-0.51 percent		-0.80 to -0.22		not stated; other; bmi:30_or_more; R0013892:Supplement Table S1
52	A1 vs A3	md	-0.63 percent		-0.92 to -0.34		not stated; other; bmi:30_or_more; R0013892:Supplement Table S1
52	A1	change	-2.40 percent	1.00		122	not stated; other; bmi:less_than_25; R0013892:Supplement Table S1
52	A1 vs A2	md	-0.60 percent		-0.78 to -0.43		not stated; other; bmi:less_than_25; R0013892:Supplement Table S1
52	A1 vs A3	md	-0.46 percent		-0.63 to -0.29		not stated; other; bmi:less_than_25; R0013892:Supplement Table S1
52	A1	change	-2.44 percent	0.68		80	not stated; other; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1
52	A1 vs A2	md	-0.65 percent		-0.87 to -0.42		not stated; other; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1
52	A1 vs A3	md	-0.47 percent		-0.70 to -0.25		not stated; other; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1
52	A1	change	-3.41 percent	0.91		88	not stated; other; hba1c:9.0_or_more; R0013892:Supplement Table S1
52	A1 vs A2	md	-0.72 percent		-0.92 to -0.52		not stated; other; hba1c:9.0_or_more; R0013892:Supplement Table S1
52	A1 vs A3	md	-0.73 percent		-0.94 to -0.51		not stated; other; hba1c:9.0_or_more; R0013892:Supplement Table S1
52	A1	change	-1.60 percent	0.53		107	not stated; other; hba1c:less_than_8.0; R0013892:Supplement Table S1
52	A1 vs A2	md	-0.54 percent		-0.73 to -0.36		not stated; other; hba1c:less_than_8.0; R0013892:Supplement Table S1
52	A1 vs A3	md	-0.32 percent		-0.50 to -0.15		not stated; other; hba1c:less_than_8.0; R0013892:Supplement Table S1
52	A1	change	-2.42 percent	1.04		275	not stated; full analysis; registry:outcomes
52	A1	change	-2.21 percent	1.03		78	not stated; other; age:65_or_older; R0013892:Supplement Table S1
52	A1 vs A2	md	-0.48 percent		-0.69 to -0.27		not stated; other; age:65_or_older; R0013892:Supplement Table S1
52	A1 vs A3	md	-0.29 percent		-0.51 to -0.07		not stated; other; age:65_or_older; R0013892:Supplement Table S1
52	A1 vs A2	md	-0.63 percent		-0.75 to -0.52		not stated; full analysis; R0014857:Results
52	A1 vs A2	md	-0.70 percent		-0.84 to -0.56		not stated; other; age:less_than_65; R0013892:Supplement Table S1
52	A1 vs A3	md	-0.55 percent		-0.69 to -0.42		not stated; other; age:less_than_65; R0013892:Supplement Table S1
52	A2	change	-1.80 percent	1.02		271	not stated; full analysis; registry:outcomes
52	A2	change	-1.08 percent	0.61		105	not stated; other; hba1c:less_than_8.0; R0013892:Supplement Table S1
52	A2	change	-2.58 percent	1.04		96	not stated; other; hba1c:9.0_or_more; R0013892:Supplement Table S1
52	A2	change	-1.54 percent	1.14		47	not stated; other; bmi:30_or_more; R0013892:Supplement Table S1
52	A2	change	-1.77 percent	0.93		88	not stated; other; age:65_or_older; R0013892:Supplement Table S1
52	A2	change	-1.79 percent	0.62		70	not stated; other; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1
52	A2	change	-1.81 percent	1.05		183	not stated; other; age:less_than_65; R0013892:Supplement Table S1
52	A2	change	-1.84 percent	0.99		117	not stated; other; bmi:less_than_25; R0013892:Supplement Table S1
52	A2	change	-1.85 percent	0.98		107	not stated; other; bmi:25_to_less_than_30; R0013892:Supplement Table S1
52	A3	change	-1.86 percent	0.88		109	not stated; other; bmi:25_to_less_than_30; R0013892:Supplement Table S1
52	A3	change	-1.30 percent	0.57		128	not stated; other; hba1c:less_than_8.0; R0013892:Supplement Table S1
52	A3	change	-1.80 percent	0.92		273	not stated; full analysis; registry:outcomes
52	A3	change	-1.92 percent	0.84		71	not stated; other; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1
52	A3	change	-1.89 percent	0.92		118	not stated; other; bmi:less_than_25; R0013892:Supplement Table S1
52	A3	change	-1.76 percent	0.93		202	not stated; other; age:less_than_65; R0013892:Supplement Table S1
52	A3	change	-2.56 percent	0.95		74	not stated; other; hba1c:9.0_or_more; R0013892:Supplement Table S1
52	A3	change	-1.91 percent	0.89		71	not stated; other; age:65_or_older; R0013892:Supplement Table S1
52	A3	change	-1.43 percent	0.94		46	not stated; other; bmi:30_or_more; R0013892:Supplement Table S1

Body weight change in kilograms (diabetes) (45 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	2.64 kg	3.29		112	not stated; other; bmi:25_to_less_than_30; R0013892:Supplement Table S1
52	A1	change	2.9 kg	3.2		275	not stated; full analysis; registry:outcomes
52	A1 vs A2	md	-1.19 kg		-1.80 to -0.59		not stated; full analysis; R0014857:Results
52	A1 vs A3	md	3.89 kg		3.29 to 4.49		not stated; full analysis; R0014857:Results
52	A1	change	2.3 kg	2.8		78	not stated; other; age:65_or_older; R0013892:Supplement Table S1
52	A1 vs A2	md	-1.35 kg		-2.45 to -0.26		not stated; other; age:65_or_older; R0013892:Supplement Table S1
52	A1 vs A3	md	3.51 kg		2.35 to 4.67		not stated; other; age:65_or_older; R0013892:Supplement Table S1
52	A1	change	3.1 kg	3.3		197	not stated; other; age:less_than_65; R0013892:Supplement Table S1
52	A1 vs A2	md	-1.17 kg		-1.89 to -0.45		not stated; other; age:less_than_65; R0013892:Supplement Table S1
52	A1 vs A3	md	4.03 kg		3.33 to 4.74		not stated; other; age:less_than_65; R0013892:Supplement Table S1
52	A1 vs A2	md	-1.40 kg		-2.36 to -0.45		not stated; other; bmi:25_to_less_than_30; R0013892:Supplement Table S1
52	A1 vs A3	md	3.97 kg		3.02 to 4.92		not stated; other; bmi:25_to_less_than_30; R0013892:Supplement Table S1
52	A1	change	3.88 kg	3.87		41	not stated; other; bmi:30_or_more; R0013892:Supplement Table S1
52	A1 vs A2	md	-0.24 kg		-1.75 to 1.26		not stated; other; bmi:30_or_more; R0013892:Supplement Table S1
52	A1 vs A3	md	4.42 kg		2.89 to 5.94		not stated; other; bmi:30_or_more; R0013892:Supplement Table S1
52	A1	change	2.77 kg	2.75		122	not stated; other; bmi:less_than_25; R0013892:Supplement Table S1
52	A1 vs A2	md	-1.33 kg		-2.24 to -0.41		not stated; other; bmi:less_than_25; R0013892:Supplement Table S1
52	A1 vs A3	md	3.64 kg		2.73 to 4.56		not stated; other; bmi:less_than_25; R0013892:Supplement Table S1
52	A1	change	2.46 kg	3.23		80	not stated; other; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1
52	A1 vs A2	md	-1.47 kg		-2.59 to -0.36		not stated; other; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1
52	A1 vs A3	md	3.36 kg		2.26 to 4.47		not stated; other; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1
52	A1	change	4.55 kg	3.14		88	not stated; other; hba1c:9.0_or_more; R0013892:Supplement Table S1
52	A1 vs A2	md	-1.12 kg		-2.12 to -0.12		not stated; other; hba1c:9.0_or_more; R0013892:Supplement Table S1
52	A1 vs A3	md	4.83 kg		3.76 to 5.90		not stated; other; hba1c:9.0_or_more; R0013892:Supplement Table S1
52	A1	change	1.82 kg	2.58		107	not stated; other; hba1c:less_than_8.0; R0013892:Supplement Table S1
52	A1 vs A2	md	-0.88 kg		-1.82 to 0.06		not stated; other; hba1c:less_than_8.0; R0013892:Supplement Table S1
52	A1 vs A3	md	3.34 kg		2.44 to 4.23		not stated; other; hba1c:less_than_8.0; R0013892:Supplement Table S1
52	A2	change	4.1 kg	4.3		271	not stated; full analysis; registry:outcomes
52	A2	change	4.13 kg	3.60		117	not stated; other; bmi:less_than_25; R0013892:Supplement Table S1
52	A2	change	5.60 kg	4.50		96	not stated; other; hba1c:9.0_or_more; R0013892:Supplement Table S1
52	A2	change	3.95 kg	5.02		70	not stated; other; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1
52	A2	change	4.3 kg	4.6		183	not stated; other; age:less_than_65; R0013892:Supplement Table S1
52	A2	change	4.17 kg	6.45		47	not stated; other; bmi:30_or_more; R0013892:Supplement Table S1
52	A2	change	3.8 kg	3.6		88	not stated; other; age:65_or_older; R0013892:Supplement Table S1
52	A2	change	2.83 kg	3.09		105	not stated; other; hba1c:less_than_8.0; R0013892:Supplement Table S1
52	A2	change	4.03 kg	3.90		107	not stated; other; bmi:25_to_less_than_30; R0013892:Supplement Table S1
52	A3	change	-1.0 kg	3.4		273	not stated; full analysis; registry:outcomes
52	A3	change	-0.78 kg	2.85		118	not stated; other; bmi:less_than_25; R0013892:Supplement Table S1
52	A3	change	-0.51 kg	4.19		46	not stated; other; bmi:30_or_more; R0013892:Supplement Table S1
52	A3	change	-1.43 kg	3.50		109	not stated; other; bmi:25_to_less_than_30; R0013892:Supplement Table S1
52	A3	change	-0.99 kg	3.21		71	not stated; other; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1
52	A3	change	-0.9 kg	3.6		202	not stated; other; age:less_than_65; R0013892:Supplement Table S1
52	A3	change	-0.33 kg	3.63		74	not stated; other; hba1c:9.0_or_more; R0013892:Supplement Table S1
52	A3	change	-1.1 kg	2.6		71	not stated; other; age:65_or_older; R0013892:Supplement Table S1
52	A3	change	-1.38 kg	3.28		128	not stated; other; hba1c:less_than_8.0; R0013892:Supplement Table S1

HbA1c below 7 percent (5 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders			245 / 275	not stated; full analysis; registry:outcomes
52	A1 vs A2	or	4.70	2.82 to 7.82		not stated; full analysis; R0014857:Results
52	A1 vs A3	or	3.90	2.31 to 6.59		not stated; full analysis; R0014857:Results
52	A2	responders			189 / 271	not stated; full analysis; registry:outcomes
52	A3	responders			208 / 273	not stated; full analysis; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (6 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	106 / 275	while on treatment; safety; R0014857:Table 2
A1	events	53 / 275	while on treatment; safety; R0014857:Table 2
A2	events	148 / 271	while on treatment; safety; R0014857:Table 2
A2	events	80 / 271	while on treatment; safety; R0014857:Table 2
A3	events	6 / 273	while on treatment; safety; R0014857:Table 2
A3	events	3 / 273	while on treatment; safety; R0014857:Table 2

Level 2 or 3 hypoglycemia (episode rate) (5 lines; O04B)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	rate	174.3		275	while on treatment; safety; R0014857:Table 2
A1 vs A2	rate ratio	0.48	0.35 to 0.68		while on treatment; safety; R0014857:Results
A1 vs A3	rate ratio	37.58	19.80 to 71.31		while on treatment; safety; R0014857:Results
A2	rate	331.9		271	while on treatment; safety; R0014857:Table 2
A3	rate	4.8		273	while on treatment; safety; R0014857:Table 2

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	1.7 mmHg	12.0		275	not stated; full analysis; registry:outcomes
52	A1 vs A2	md	-2.05 mmHg		-4.02 to -0.08		not stated; full analysis; R0014857:Results
52	A1 vs A3	md	2.88 mmHg		0.91 to 4.85		not stated; full analysis; R0014857:Results
52	A2	change	3.4 mmHg	14.3		271	not stated; full analysis; registry:outcomes
52	A3	change	-1.8 mmHg	13.0		273	not stated; full analysis; registry:outcomes

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	1 / 275	while on treatment; safety; registry:adverse_events
A2	events	0 / 271	while on treatment; safety; registry:adverse_events
A3	events	0 / 273	while on treatment; safety; registry:adverse_events

Three point MACE (1 lines; O21)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A3	events				0 / 273	while on treatment; safety; R0014857:Results

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	17 / 275	while on treatment; safety; R0014857:Table 2
A2	events	13 / 271	while on treatment; safety; R0014857:Table 2
A3	events	14 / 273	while on treatment; safety; R0014857:Table 2

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	8 / 275	not stated; randomized; R0014857:Results
A2	events	6 / 271	not stated; randomized; R0014857:Results
A3	events	6 / 273	not stated; randomized; R0014857:Results

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	9 / 275	while on treatment; safety; R0014857:Table 2
A2	events	5 / 271	while on treatment; safety; R0014857:Table 2
A3	events	23 / 273	while on treatment; safety; R0014857:Table 2

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	15 / 275	while on treatment; safety; R0014857:Table 2
A2	events	12 / 271	while on treatment; safety; R0014857:Table 2
A3	events	24 / 273	while on treatment; safety; R0014857:Table 2

Constipation (3 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	27 / 275	while on treatment; safety; R0014857:Table 2
A2	events	12 / 271	while on treatment; safety; R0014857:Table 2
A3	events	38 / 273	while on treatment; safety; R0014857:Table 2

Gallbladder and biliary disease (6 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 275	while on treatment; safety; cholecystitis acute; registry:adverse_events
A1	events	1 / 275	while on treatment; safety; cholecystitis; registry:adverse_events
A2	events	0 / 271	while on treatment; safety; cholecystitis acute; registry:adverse_events
A2	events	0 / 271	while on treatment; safety; cholecystitis; registry:adverse_events
A3	events	1 / 273	while on treatment; safety; cholecystitis acute; registry:adverse_events
A3	events	0 / 273	while on treatment; safety; cholecystitis; registry:adverse_events

Acute pancreatitis (7 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 275	while on treatment; safety; registry:adverse_events
A1	events	1 / 275	while on treatment; safety; R0014857:Results
A1	events	0 / 275	while on treatment; safety; autoimmune pancreatitis; registry:adverse_events
A2	events	0 / 271	while on treatment; safety; registry:adverse_events
A2	events	0 / 271	while on treatment; safety; autoimmune pancreatitis; registry:adverse_events
A3	events	0 / 273	while on treatment; safety; registry:adverse_events
A3	events	1 / 273	while on treatment; safety; autoimmune pancreatitis; registry:adverse_events

Medullary thyroid carcinoma (3 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 275	while on treatment; safety; R0014857:Results
A2	events	0 / 271	while on treatment; safety; R0014857:Results
A3	events	0 / 273	while on treatment; safety; R0014857:Results

Thyroid cancer (any) (3 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 275	while on treatment; safety; R0014857:Results
A2	events	0 / 271	while on treatment; safety; R0014857:Results
A3	events	0 / 273	while on treatment; safety; R0014857:Results

Diabetic retinopathy complications (3 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	17 / 275	while on treatment; safety; diabetic retinopathy; R0014857:Table 2
A2	events	12 / 271	while on treatment; safety; diabetic retinopathy; R0014857:Table 2
A3	events	11 / 273	while on treatment; safety; diabetic retinopathy; R0014857:Table 2

Suicidal ideation or behavior (3 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 275	while on treatment; safety; suicide attempt; registry:adverse_events
A2	events	0 / 271	while on treatment; safety; suicide attempt; registry:adverse_events
A3	events	1 / 273	while on treatment; safety; suicide attempt; registry:adverse_events

Death by suicide (3 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 275	while on treatment; safety; registry:adverse_events
A2	events	0 / 271	while on treatment; safety; registry:adverse_events
A3	events	0 / 273	while on treatment; safety; registry:adverse_events

Any cancer (2 lines; O39)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 275	while on treatment; safety; R0014857:Results
	A2	events				1 / 271	while on treatment; safety; R0014857:Results