parallel randomized trial

NCT01512108

A 52-week, Multi-centre, Open-labelled, Randomised (2:1), Parallel-group Trial With an Active Control (Two OADs Combination Therapy) to Evaluate the Safety and Efficacy of Liraglutide in Combination With an OAD in Subjects With Type 2 Diabetes Insufficiently Controlled on OAD Monotherapy

Type 2 diabetes (adults)NCT01512108S000233

Design

Randomized: 363
Start year: 2012
Treatment: 52 weeks, follow-up 52 weeks
Countries: Japan (36 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 20 or older; HbA1c 7.0 to 10.0 percent on one oral agent; BMI below 40

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	Completed treatment
A1	liraglutide Liraglutide 0.9 mg plus pretrial oral agent	pretrial oral agent monotherapy (glinide, metformin, alpha glucosidase inhibitor or thiazolidinedione); lifestyle: standard	243	240
A2	Oral investigator choice Additional OAD	pretrial OAD monotherapy (glinide, metformin, alpha glucosidase inhibitor or thiazolidinedione); lifestyle: standard	120	120

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Liraglutide 0.9 mg plus pretrial oral agent A1	Oral investigator choice A2
age	mean (years)	59.6	59.2
age	sd (years)	11.6	10.2
bmi	mean (kg/m2)	25.7	25.5
bmi	sd (kg/m2)	4.2	3.7
diabetes duration	mean (years)	7.80	8.47
diabetes duration	sd (years)	5.77	6.55
female	n	58	40
hba1c	mean (percent)	8.1	8.1
hba1c	sd (percent)	0.8	0.8
other background: alpha glucosidase inhibitor only	n	63	30
other background: alpha glucosidase inhibitor only	percent	26.3	25.0
other background: glinide only	n	58	31
other background: glinide only	percent	24.2	25.8
other background: metformin only	n	61	31
other background: metformin only	percent	25.4	25.8
other background: thiazolidinedione only	n	58	28
other background: thiazolidinedione only	percent	24.2	23.3
weight	mean (kg)	69.4	68.2
weight	sd (kg)	14.2	13.6

Results

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

HbA1c change (19 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-1.21 percent	0.05		239	not stated; full analysis; registry:outcomes
52	A1	change	-1.06 percent				not stated; full analysis; background:metformin_only; R0011989:Table 3
52	A1 vs A2	md	-0.14 percent		-0.48 to 0.21		not stated; full analysis; background:metformin_only; R0011989:Table 3
52	A1	final	6.8 percent	1.0			not stated; full analysis; R0026134:Results
52	A1	change	-1.41 percent				not stated; full analysis; background:thiazolidinedione_only; R0011989:Table 3
52	A1 vs A2	md	-0.35 percent		-0.71 to 0.01		not stated; full analysis; background:thiazolidinedione_only; R0011989:Table 3
52	A1	change	-1.29 percent				not stated; full analysis; background:alpha_glucosidase_inhibitor_only; R0011989:Table 3
52	A1 vs A2	md	-0.44 percent		-0.79 to -0.09		not stated; full analysis; background:alpha_glucosidase_inhibitor_only; R0011989:Table 3
52	A1 vs A2	md	-0.27 percent		-0.44 to -0.09		not stated; full analysis; R0026134:Table 3
52	A1	change	-1.21 percent				not stated; full analysis; R0026134:Table 3
52	A1	change	-1.08 percent				not stated; full analysis; background:glinide_only; R0011989:Table 3
52	A1 vs A2	md	-0.15 percent		-0.50 to 0.20		not stated; full analysis; background:glinide_only; R0011989:Table 3
52	A2	change	-1.06 percent				not stated; full analysis; background:thiazolidinedione_only; R0011989:Table 3
52	A2	change	-0.94 percent	0.07		120	not stated; full analysis; registry:outcomes
52	A2	final	7.1 percent	0.8			not stated; full analysis; R0026134:Results
52	A2	change	-0.85 percent				not stated; full analysis; background:alpha_glucosidase_inhibitor_only; R0011989:Table 3
52	A2	change	-0.93 percent				not stated; full analysis; background:glinide_only; R0011989:Table 3
52	A2	change	-0.92 percent				not stated; full analysis; background:metformin_only; R0011989:Table 3
52	A2	change	-0.94 percent				not stated; full analysis; R0026134:Table 3

Body weight change in kilograms (diabetes) (15 lines; O02)

Week	Arm	Statistic	Estimate	95% CI	Detail
52	A1	change	-1.58 kg		not stated; full analysis; background:metformin_only; R0011989:Table 3
52	A1	change	0.20 kg		not stated; full analysis; background:thiazolidinedione_only; R0011989:Table 3
52	A1 vs A2	md	0.31 kg	-1.01 to 1.63	not stated; full analysis; background:thiazolidinedione_only; R0011989:Table 3
52	A1	change	-0.85 kg		not stated; full analysis; R0026134:Table 3
52	A1 vs A2	md	-0.35 kg	-0.99 to 0.29	not stated; full analysis; R0026134:Table 3
52	A1	change	-1.30 kg		not stated; full analysis; background:alpha_glucosidase_inhibitor_only; R0011989:Table 3
52	A1 vs A2	md	-0.74 kg	-2.01 to 0.54	not stated; full analysis; background:alpha_glucosidase_inhibitor_only; R0011989:Table 3
52	A1	change	-0.64 kg		not stated; full analysis; background:glinide_only; R0011989:Table 3
52	A1 vs A2	md	-0.10 kg	-1.37 to 1.18	not stated; full analysis; background:glinide_only; R0011989:Table 3
52	A1 vs A2	md	-0.84 kg	-2.01 to 0.43	not stated; full analysis; background:metformin_only; R0011989:Table 3
52	A2	change	-0.11 kg		not stated; full analysis; background:thiazolidinedione_only; R0011989:Table 3
52	A2	change	-0.50 kg		not stated; full analysis; R0026134:Table 3
52	A2	change	-0.56 kg		not stated; full analysis; background:alpha_glucosidase_inhibitor_only; R0011989:Table 3
52	A2	change	-0.55 kg		not stated; full analysis; background:glinide_only; R0011989:Table 3
52	A2	change	-0.75 kg		not stated; full analysis; background:metformin_only; R0011989:Table 3

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1 vs A2	or	2.57	1.54 to 4.28		not stated; full analysis; R0026134:Table 3
52	A1	responders	67.6		240	not stated; full analysis; R0026134:Table 3
52	A2	responders	44.8		120	not stated; full analysis; R0026134:Table 3

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 240	not stated; safety; R0026134:Results
A1	events	2 / 240	not stated; safety; R0026134:Results
A2	events	2 / 120	not stated; safety; R0026134:Results
A2	events	0 / 120	not stated; safety; R0026134:Results

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	rate				240	not stated; safety; R0026134:Results
	A2	rate				120	not stated; safety; R0026134:Results

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Detail
52	A1	change	-4.00 mmHg		not stated; safety; R0026134:Results
52	A1 vs A2	md	-0.10 mmHg	-2.54 to 2.35	not stated; safety; R0026134:Results
52	A2	change	-3.91 mmHg		not stated; safety; R0026134:Results

All cause mortality (1 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 240	while on treatment; safety; R0026134:Results

Hospitalization for heart failure (2 lines; O23)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 240	not stated; safety; cardiac failure; registry:adverse_events
	A2	events				0 / 120	not stated; safety; cardiac failure; registry:adverse_events

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				11 / 240	while on treatment; safety; R0026134:Table 2
	A2	events				10 / 120	while on treatment; safety; R0026134:Table 2

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 243	not stated; randomized; R0026134:Results
	A2	events				4 / 120	not stated; randomized; R0026134:Results

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				31 / 240	while on treatment; safety; R0026134:Table 2
	A2	events				4 / 120	while on treatment; safety; R0026134:Table 2

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				20 / 240	while on treatment; safety; R0026134:Table 2
	A2	events				9 / 120	while on treatment; safety; R0026134:Table 2

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				44 / 240	while on treatment; safety; R0026134:Table 2
	A2	events				12 / 120	while on treatment; safety; R0026134:Table 2

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 240	while on treatment; safety; pancreatitis; R0026134:Results
	A2	events				0 / 120	while on treatment; safety; pancreatitis; R0026134:Results

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	21 / 240	while on treatment; safety; diabetic retinopathy; R0026134:Table 2
A1	events	1 / 240	not stated; safety; diabetic retinopathy; registry:adverse_events
A2	events	0 / 120	not stated; safety; diabetic retinopathy; registry:adverse_events
A2	events	16 / 120	while on treatment; safety; diabetic retinopathy; R0026134:Table 2

Death by suicide (1 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 240	while on treatment; safety; R0026134:Results