parallel randomized trial

DUAL™ III

The Efficacy of Insulin Degludec/Liraglutide in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on GLP-1 Receptor Agonist and OAD Therapy (DUAL™ III -GLP-1 Switch)

Type 2 diabetes (adults)NCT01676116S001654

Design

Randomized: 438
Start year: 2012
Treatment: 26 weeks, follow-up 27 weeks
Countries: Australia, France, Hungary, Slovakia, United States (81 sites)
Sponsor: Novo Nordisk (industry)
Eligibility: age 18 or older, HbA1c 7.0 to 9.0 percent, BMI 40 or less, on GLP-1 RA plus OADs, insulin naive

Conduct and analysis

Blinding: open label
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 plus OADs	metformin with or without pioglitazone or sulfonylurea; pretrial GLP-1 RA stopped; lifestyle: not reported	292	292
A2	liraglutide or exenatide Unchanged GLP-1 RA plus OADs	metformin with or without pioglitazone or sulfonylurea; lifestyle: not reported	146	146

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	Unchanged GLP-1 RA plus OADs A2
age	mean (years)	58.3	58.4
age	sd (years)	9.9	8.8
asian	percent	2.1	1.4
black	percent	5.1	8.2
bmi	mean (kg/m2)	32.9	33.0
bmi	sd (kg/m2)	4.4	4.1
diabetes duration	mean (years)	10.4	10.4
diabetes duration	sd (years)	5.8	5.8
female	n	139	75
female	percent	47.6	51.4
hba1c	mean (percent)	7.8	7.7
hba1c	sd (percent)	0.6	0.6
hispanic	percent	8.9	10.3
other background: metformin only	percent	74.3	74.0
other background: metformin pioglitazone	percent	2.4	2.7
other background: metformin sulfonylurea pioglitazone	percent	2.4	1.4
other background: metformin sulfonylurea	percent	20.9	21.9
other race american indian alaska native	percent	0.3	0.0
other race other	percent	0.3	0.7
weight	mean (kg)	95.6	95.5
weight	sd (kg)	16.6	17.3
white	percent	92.1	89.7

Results

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

HbA1c change (5 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.3 percent	0.8		292	not stated; full analysis; R0008329:Results
26	A1 vs A2	md	-0.94 percent		-1.11 to -0.78		not stated; full analysis; R0008329:Results
26	A1	change	-1.32 percent	0.05		292	not stated; full analysis; registry:outcomes
26	A2	change	-0.37 percent	0.07		146	not stated; full analysis; registry:outcomes
26	A2	change	-0.3 percent	0.9		146	not stated; full analysis; R0008329:Results

Body weight change in kilograms (diabetes) (3 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	2.0 kg	3.9		292	not stated; full analysis; R0008329:Results
26	A1 vs A2	md	2.89 kg		2.17 to 3.62		not stated; full analysis; R0008329:Results
26	A2	change	-0.8 kg	3.0		146	not stated; full analysis; R0008329:Results

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1 vs A2	or	6.84	4.28 to 10.94		not stated; full analysis; R0008329:Results
26	A1	responders	75		292	not stated; full analysis; R0008329:Results
26	A2	responders	36		146	not stated; full analysis; R0008329:Results

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

Arm	Statistic	Events / N	Detail
A1	events	1 / 291	not stated; safety; R0008329:Supplement Table S3
A1	events	93 / 291	not stated; safety; R0008329:Supplement Table S3
A2	events	0 / 145	not stated; safety; R0008329:Supplement Table S3
A2	events	4 / 145	not stated; safety; R0008329:Supplement Table S3

Level 2 or 3 hypoglycemia (episode rate) (1 lines; O04B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1 vs A2	rate ratio	25.36		10.6 to 60.5		not stated; full analysis; R0008329:Supplement Table S3

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 291	not stated; safety; R0008329:Table 2
	A2	events				0 / 145	not stated; safety; R0008329:Table 2

Three point MACE (1 lines; O21)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	events				0 / 145	not stated; safety; R0008329:Results

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 vs A2	md	5.0 points		2.9 to 7.2		not stated; full analysis; R0008329:Supplement Table S6
26	A1	change	3.1 points	5.6		290	not stated; full analysis; R0008329:Supplement Table S6
26	A1	change	8.7 points	12.0		290	not stated; full analysis; R0008329:Supplement Table S6
26	A1 vs A2	md	2.0 points		1.1 to 2.8		not stated; full analysis; R0008329:Supplement Table S6
26	A2	change	1.1 points	5.0		146	not stated; full analysis; R0008329:Supplement Table S6
26	A2	change	3.1 points	12.2		146	not stated; full analysis; R0008329:Supplement Table S6

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 291	not stated; safety; R0008329:Table 2
	A2	events				3 / 145	not stated; safety; R0008329:Table 2

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 292	not stated; randomized; R0008329:Results
	A2	events				2 / 146	not stated; randomized; R0008329:Results

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events	3.1			291	not stated; safety; R0008329:Results
	A2	events	4.1			145	not stated; safety; R0008329:Results

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				13 / 291	not stated; safety; registry:adverse_events
	A2	events				8 / 145	not stated; safety; registry:adverse_events

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	events				1 / 146	not stated; randomized; abdominal discomfort; R0008329:Results

Gallbladder and biliary disease (4 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 291	not stated; safety; cholecystitis acute; registry:adverse_events
A1	events	0 / 291	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	0 / 145	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	1 / 145	not stated; safety; cholelithiasis; registry:adverse_events

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 291	not stated; safety; R0008329:Results
	A2	events				0 / 145	not stated; safety; R0008329:Results

Medullary thyroid carcinoma (2 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 291	not stated; safety; R0008329:Results
	A2	events				0 / 145	not stated; safety; R0008329:Results

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 291	not stated; safety; R0008329:Results
	A2	events				0 / 145	not stated; safety; R0008329:Results