parallel randomized trial

DUAL™ II Japan

A Double-blinded Trial Comparing the Efficacy and Safety of Insulin Degludec/Liraglutide and Insulin Degludec Both in Combination With Metformin in Japanese Subjects With Type 2 Diabetes Mellitus Inadequately Controlled With Basal or Pre-mix/Combination Insulin Therapy and Oral Anti-diabetic Drugs

Type 2 diabetes (adults)NCT02911948S002038

Design

Randomized: 210
Start year: 2016
Treatment: 26 weeks, follow-up 27 weeks
Countries: Japan
Sponsor: Novo Nordisk A/S (industry)
Eligibility: Japanese adults; BMI 23 kg/m2 or more; HbA1c 7.5 to 11.0 percent; basal or premix insulin 20 to 50 U with metformin

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: not stated
Analysis population: full analysis
Missing data: LOCF

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Insulin degludec and liraglutide (IDegLira) subcutaneous once daily titrated IDegLira	metformin at pretrial dose; other OADs and prior insulin stopped; lifestyle: not reported	105	105
A2	Insulin degludec Insulin degludec (capped at 50 U)	metformin at pretrial dose; other OADs and prior insulin stopped; lifestyle: not reported	105	105

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
age: 65 or older	n	30	20
age: 65 or older	percent	29	19
age: less than 65	n	75	85
age: less than 65	percent	71	81
age	mean (years)	56.6	55.5
age	sd (years)	10.4	10.0
asian	n	105	105
black	n	0	0
bmi: 25 to less than 30	n	64	53
bmi: 25 to less than 30	percent	61	50
bmi: 30 or more	n	15	24
bmi: 30 or more	percent	14	23
bmi: less than 25	n	26	28
bmi: less than 25	percent	25	27
bmi	mean (kg/m2)	27.3	28.1
bmi	sd (kg/m2)	3.1	4.4
diabetes duration	mean (years)	14.33	13.77
diabetes duration	sd (years)	7.79	7.46
female	n	35	42
hba1c: 8.0 to less than 9.0	n	40	46
hba1c: 8.0 to less than 9.0	percent	38	44
hba1c: 9.0 or more	n	36	32
hba1c: 9.0 or more	percent	34	30
hba1c: less than 8.0	n	29	27
hba1c: less than 8.0	percent	28	26
hba1c	mean (percent)	8.61	8.56
hba1c	sd (percent)	0.88	0.80
other race american indian alaska native	n	0	0
other race multiple	n	0	0
other race native hawaiian pacific islander	n	0	0
weight	mean (kg)	73.9	75.5
weight	sd (kg)	11.9	14.0
white	n	0	0

Analyses this trial contributes to

Results

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

HbA1c change (37 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A2	md	-1.36 percent		-1.90 to -0.83		not stated; full analysis; bmi:30_or_more; R0013892:Supplement Table S1b
26	A1 vs A2	md	-1.27 percent		-1.52 to -1.01		not stated; full analysis; age:less_than_65; R0013892:Supplement Table S1b
26	A1	change	-1.93 percent	0.98		26	not stated; full analysis; bmi:less_than_25; R0013892:Supplement Table S1b
26	A1 vs A2	md	-1.49 percent		-1.94 to -1.05		not stated; full analysis; bmi:less_than_25; R0013892:Supplement Table S1b
26	A1	change	-1.95 percent	1.01		105	not stated; full analysis; registry:outcomes
26	A1	change	-1.87 percent	0.71		40	not stated; full analysis; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1b
26	A1 vs A2	md	-1.32 percent		-1.67 to -0.97		not stated; full analysis; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1b
26	A1	change	-1.58 percent			39	not stated; full analysis; background:prior_premixed_insulin; R0022345:Figure 1
26	A1	change	-2.66 percent	0.95		36	not stated; full analysis; hba1c:9.0_or_more; R0013892:Supplement Table S1b
26	A1 vs A2	md	-1.61 percent		-2.00 to -1.22		not stated; full analysis; hba1c:9.0_or_more; R0013892:Supplement Table S1b
26	A1 vs A2	md	-1.28 percent		-1.50 to -1.06		not stated; full analysis; R0015589:Results
26	A1	change	-1.18 percent	0.82		29	not stated; full analysis; hba1c:less_than_8.0; R0013892:Supplement Table S1b
26	A1 vs A2	md	-0.82 percent		-1.26 to -0.39		not stated; full analysis; hba1c:less_than_8.0; R0013892:Supplement Table S1b
26	A1	final	6.68 percent	0.93		39	not stated; full analysis; background:prior_premixed_insulin; R0022345:Results
26	A1	change	-1.58 percent	0.87		30	not stated; full analysis; age:65_or_older; R0013892:Supplement Table S1b
26	A1	change	-2.17 percent			66	not stated; full analysis; background:prior_basal_insulin; R0022345:Figure 1
26	A1	final	6.64 percent	0.72		66	not stated; full analysis; background:prior_basal_insulin; R0022345:Results
26	A1 vs A2	md	-1.36 percent		-1.83 to -0.89		not stated; full analysis; age:65_or_older; R0013892:Supplement Table S1b
26	A1	change	-1.89 percent	1.07		64	not stated; full analysis; bmi:25_to_less_than_30; R0013892:Supplement Table S1b
26	A1 vs A2	md	-1.15 percent		-1.46 to -0.85		not stated; full analysis; bmi:25_to_less_than_30; R0013892:Supplement Table S1b
26	A1	change	-1.95 percent			105	not stated; full analysis; R0015589:Results
26	A1	change	-2.10 percent	1.03		75	not stated; full analysis; age:less_than_65; R0013892:Supplement Table S1b
26	A1	change	-2.25 percent	0.72		15	not stated; full analysis; bmi:30_or_more; R0013892:Supplement Table S1b
26	A2	change	-0.32 percent	0.76		27	not stated; full analysis; hba1c:less_than_8.0; R0013892:Supplement Table S1b
26	A2	change	-0.92 percent			67	not stated; full analysis; background:prior_basal_insulin; R0022345:Figure 1
26	A2	final	7.77 percent	1.04		67	not stated; full analysis; background:prior_basal_insulin; R0022345:Results
26	A2	change	-0.65 percent			105	not stated; full analysis; R0015589:Results
26	A2	change	-0.65 percent	0.98		105	not stated; full analysis; registry:outcomes
26	A2	change	-0.16 percent			38	not stated; full analysis; background:prior_premixed_insulin; R0022345:Figure 1
26	A2	final	8.18 percent	1.03		38	not stated; full analysis; background:prior_premixed_insulin; R0022345:Results
26	A2	change	-0.39 percent	0.97		20	not stated; full analysis; age:65_or_older; R0013892:Supplement Table S1b
26	A2	change	-0.68 percent	1.11		53	not stated; full analysis; bmi:25_to_less_than_30; R0013892:Supplement Table S1b
26	A2	change	-0.69 percent	0.83		24	not stated; full analysis; bmi:30_or_more; R0013892:Supplement Table S1b
26	A2	change	-0.54 percent	0.86		28	not stated; full analysis; bmi:less_than_25; R0013892:Supplement Table S1b
26	A2	change	-0.56 percent	1.06		46	not stated; full analysis; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1b
26	A2	change	-1.04 percent	0.92		32	not stated; full analysis; hba1c:9.0_or_more; R0013892:Supplement Table S1b
26	A2	change	-0.71 percent	0.98		85	not stated; full analysis; age:less_than_65; R0013892:Supplement Table S1b

Body weight change in kilograms (diabetes) (33 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.5 kg	2.9		39	not stated; full analysis; background:prior_premixed_insulin; R0022345:Results
26	A1 vs A2	md	-0.66 kg		-2.33 to 1.02		not stated; full analysis; bmi:less_than_25; R0013892:Supplement Table S1d
26	A1	change	-1.24 kg	3.97		40	not stated; full analysis; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1d
26	A1 vs A2	md	-2.29 kg		-3.63 to -0.96		not stated; full analysis; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1d
26	A1	change	0.34 kg	3.02		36	not stated; full analysis; hba1c:9.0_or_more; R0013892:Supplement Table S1d
26	A1 vs A2	md	-0.06 kg		-1.56 to 1.43		not stated; full analysis; hba1c:9.0_or_more; R0013892:Supplement Table S1d
26	A1	change	-1.28 kg	3.13		29	not stated; full analysis; hba1c:less_than_8.0; R0013892:Supplement Table S1d
26	A1 vs A2	md	-1.78 kg		-3.45 to -0.11		not stated; full analysis; hba1c:less_than_8.0; R0013892:Supplement Table S1d
26	A1	change	-0.7 kg			105	not stated; full analysis; R0015589:Results
26	A1	change	-0.7 kg	3.5		105	not stated; full analysis; registry:outcomes
26	A1 vs A2	md	-1.41 kg		-2.26 to -0.56		not stated; full analysis; R0015589:Results
26	A1	change	-1.6 kg	2.9		30	not stated; full analysis; age:65_or_older; R0013892:Supplement Table S1d
26	A1 vs A2	md	-1.30 kg		-3.08 to 0.48		not stated; full analysis; age:65_or_older; R0013892:Supplement Table S1d
26	A1	change	-0.4 kg	3.7		75	not stated; full analysis; age:less_than_65; R0013892:Supplement Table S1d
26	A1 vs A2	md	-1.35 kg		-2.32 to -0.37		not stated; full analysis; age:less_than_65; R0013892:Supplement Table S1d
26	A1	change	-0.3 kg	3.7		66	not stated; full analysis; background:prior_basal_insulin; R0022345:Results
26	A1	change	-0.15 kg	1.78		26	not stated; full analysis; bmi:less_than_25; R0013892:Supplement Table S1d
26	A1	change	-1.13 kg	3.84		64	not stated; full analysis; bmi:25_to_less_than_30; R0013892:Supplement Table S1d
26	A1 vs A2	md	-2.04 kg		-3.18 to -0.90		not stated; full analysis; bmi:25_to_less_than_30; R0013892:Supplement Table S1d
26	A1	change	0.09 kg	4.05		15	not stated; full analysis; bmi:30_or_more; R0013892:Supplement Table S1d
26	A1 vs A2	md	-0.38 kg		-2.41 to 1.64		not stated; full analysis; bmi:30_or_more; R0013892:Supplement Table S1d
26	A2	change	-0.2 kg	2.7		20	not stated; full analysis; age:65_or_older; R0013892:Supplement Table S1d
26	A2	change	0.7 kg			105	not stated; full analysis; R0015589:Results
26	A2	change	0.7 kg	2.7		105	not stated; full analysis; registry:outcomes
26	A2	change	0.9 kg	2.7		85	not stated; full analysis; age:less_than_65; R0013892:Supplement Table S1d
26	A2	change	1.1 kg	2.7		67	not stated; full analysis; background:prior_basal_insulin; R0022345:Results
26	A2	change	0.1 kg	2.8		38	not stated; full analysis; background:prior_premixed_insulin; R0022345:Results
26	A2	change	0.84 kg	3.21		53	not stated; full analysis; bmi:25_to_less_than_30; R0013892:Supplement Table S1d
26	A2	change	0.61 kg	2.44		24	not stated; full analysis; bmi:30_or_more; R0013892:Supplement Table S1d
26	A2	change	0.65 kg	2.02		28	not stated; full analysis; bmi:less_than_25; R0013892:Supplement Table S1d
26	A2	change	0.87 kg	2.69		46	not stated; full analysis; hba1c:8.0_to_less_than_9.0; R0013892:Supplement Table S1d
26	A2	change	0.57 kg	2.40		32	not stated; full analysis; hba1c:9.0_or_more; R0013892:Supplement Table S1d
26	A2	change	0.70 kg	3.28		27	not stated; full analysis; hba1c:less_than_8.0; R0013892:Supplement Table S1d

HbA1c below 7 percent (2 lines; O03)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	responders				75 / 105	not stated; full analysis; registry:outcomes
26	A2	responders				23 / 105	not stated; full analysis; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (4 lines; O04)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	28.6	105	while on treatment; safety; R0015589:Results
A1	events	14.3	105	while on treatment; safety; R0015589:Results
A2	events	30.5	105	while on treatment; safety; R0015589:Results
A2	events	17.1	105	while on treatment; safety; R0015589:Results

Level 2 or 3 hypoglycemia (episode rate) (4 lines; O04B)

Arm	Statistic	Estimate	95% CI	Detail
A1	rate			while on treatment; safety; registry:outcomes
A1 vs A2	rate ratio	1.16	0.57 to 2.34	while on treatment; full analysis; R0015589:Results
A1 vs A2	rate ratio	1.05	0.40 to 2.77	while on treatment; full analysis; R0015589:Results
A2	rate			while on treatment; safety; registry:outcomes

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-0.6 mmHg	14.7		105	not stated; full analysis; registry:outcomes
26	A1 vs A2	md	-0.57 mmHg		-4.17 to 3.04		not stated; full analysis; R0015589:Results
26	A2	change	0.9 mmHg	13.6		105	not stated; full analysis; registry:outcomes

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 105	while on treatment; safety; R0015589:Results
	A2	events				0 / 105	while on treatment; safety; R0015589:Results

Three point MACE (3 lines; O21)

Arm	Statistic	Events / N	Detail
A1	events	1 / 105	while on treatment; safety; R0015589:Results
A1	events	1 / 105	while on treatment; safety; acute myocardial infarction; registry:adverse_events
A2	events	0 / 105	while on treatment; safety; acute myocardial infarction; registry:adverse_events

Hospitalization for heart failure (2 lines; O23)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 105	while on treatment; safety; cardiac failure congestive; registry:adverse_events
	A2	events				0 / 105	while on treatment; safety; cardiac failure congestive; registry:adverse_events

Health related quality of life total score (any instrument) (6 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	7.9 points	14.8		105	not stated; full analysis; registry:outcomes
26	A1	change	0.02 points	0.08		105	not stated; full analysis; registry:outcomes
26	A1 vs A2	md	7.39 points		3.82 to 10.97		not stated; full analysis; R0015589:Results
26	A1 vs A2	md	0.03 points		0.01 to 0.05		not stated; full analysis; R0015589:Results
26	A2	change	0.1 points	13.4		105	not stated; full analysis; registry:outcomes
26	A2	change	-0.01 points	0.11		105	not stated; full analysis; registry:outcomes

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				3 / 105	while on treatment; safety; R0015589:Table 2
	A2	events				4 / 105	while on treatment; safety; R0015589:Table 2

Discontinuation due to adverse events (1 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 105	not stated; randomized; R0015589:Results

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				10 / 105	while on treatment; safety; R0015589:Table 2
	A2	events				4 / 105	while on treatment; safety; R0015589:Table 2

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 105	while on treatment; safety; R0015589:Table 2
	A2	events				2 / 105	while on treatment; safety; R0015589:Table 2

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				15 / 105	while on treatment; safety; R0015589:Table 2
	A2	events				5 / 105	while on treatment; safety; R0015589:Table 2

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 105	while on treatment; safety; R0015589:Table 2
	A2	events				4 / 105	while on treatment; safety; R0015589:Table 2

Discontinuation due to gastrointestinal adverse events (1 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 105	not stated; randomized; R0015589:Results

Gallbladder and biliary disease (2 lines; O28)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 105	while on treatment; safety; cholecystitis acute; registry:adverse_events
	A2	events				1 / 105	while on treatment; safety; cholecystitis acute; registry:adverse_events

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 105	while on treatment; safety; R0015589:Results
	A2	events				0 / 105	while on treatment; safety; R0015589:Results

Diabetic retinopathy complications (2 lines; O33)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				17 / 105	while on treatment; safety; diabetic retinopathy; R0015589:Table 2
	A2	events				17 / 105	while on treatment; safety; diabetic retinopathy; R0015589:Table 2

Pancreatic cancer (2 lines; O38)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 105	while on treatment; safety; registry:adverse_events
	A2	events				1 / 105	while on treatment; safety; registry:adverse_events