parallel randomized trial

NCT01572740

A 36-week, Randomised, Multi-centre, Double-blind, Parallel Group Trial to Investigate the Efficacy and Safety of Liraglutide in Combination With Insulin Therapy Compared to Insulin Monotherapy in Japanese Subjects With Type 2 Diabetes Mellitus

Type 2 diabetes (adults)NCT01572740S000361

Design

Randomized: 257
Start year: 2012
Treatment: 36 weeks, follow-up 36 weeks
Countries: Japan (23 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 20 or more; HbA1c 7.5 to 11.0 percent; BMI below 45; stable basal, premix or basal bolus insulin

Conduct and analysis

Blinding: double blind
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 + insulin	pretrial insulin (basal, premixed or basal bolus), fixed to week 16 then titrated; lifestyle: not reported	127	127
A2	Placebo Liraglutide placebo + insulin	pretrial insulin (basal, premixed or basal bolus), fixed to week 16 then titrated; lifestyle: not reported	130	130

Baseline characteristics

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

Characteristic	Statistic	Liraglutide + insulin A1	Placebo A2
age	mean (years)	61.3	59.8
age	sd (years)	11.0	11.3
bmi	mean (kg/m2)	26.2	25.2
bmi	sd (kg/m2)	4.9	4.0
diabetes duration	mean (years)	14.32	14.69
diabetes duration	sd (years)	8.89	8.60
female	n	58	55
hba1c	mean (percent)	8.8	8.8
hba1c	sd (percent)	0.9	0.9
insulin dose	mean (U/day)	30	29
insulin dose	sd (U/day)	14	17
other background: basal bolus insulin only	n	27	28
other background: basal bolus insulin only	percent	21.3	21.5
other background: basal insulin only	n	50	50
other background: basal insulin only	percent	39.4	38.5
other background: premixed insulin only	n	50	52
other background: premixed insulin only	percent	39.4	40.0
weight	mean (kg)	67.7	65.9
weight	sd (kg)	15.2	13.0

Results

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

HbA1c change (14 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
36	A1 vs A2	md	-0.76 percent		-1.05 to -0.48		not stated; full analysis; background:premixed_insulin; R0025067:Table 2
36	A1	change	-1.68 percent			127	not stated; full analysis; R0026074:Figure 2
36	A1	change	-1.68 percent	0.06		127	not stated; full analysis; registry:outcomes
36	A1 vs A2	md	-0.81 percent		-0.99 to -0.63		not stated; full analysis; R0026074:Results
36	A1	change	-1.52 percent				not stated; full analysis; background:basal_bolus_insulin; R0025067:Table 2
36	A1 vs A2	md	-0.65 percent		-1.04 to -0.26		not stated; full analysis; background:basal_bolus_insulin; R0025067:Table 2
36	A1	change	-1.53 percent				not stated; full analysis; background:basal_insulin; R0025067:Table 2
36	A1 vs A2	md	-0.94 percent		-1.23 to -0.66		not stated; full analysis; background:basal_insulin; R0025067:Table 2
36	A1	change	-1.92 percent				not stated; full analysis; background:premixed_insulin; R0025067:Table 2
36	A2	change	-0.88 percent			129	not stated; full analysis; R0026074:Figure 2
36	A2	change	-0.88 percent	0.06		129	not stated; full analysis; registry:outcomes
36	A2	change	-0.59 percent				not stated; full analysis; background:basal_insulin; R0025067:Table 2
36	A2	change	-1.16 percent				not stated; full analysis; background:premixed_insulin; R0025067:Table 2
36	A2	change	-0.87 percent				not stated; full analysis; background:basal_bolus_insulin; R0025067:Table 2

Body weight change in kilograms (diabetes) (14 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
36	A1 vs A2	md	-0.96 kg		-1.83 to -0.08		not stated; full analysis; background:premixed_insulin; R0025067:Table 2
36	A1	change	0.17 kg				not stated; full analysis; R0026074:Results
36	A1	change	0.17 kg	0.20		127	not stated; full analysis; registry:outcomes
36	A1 vs A2	md	-0.35 kg		-0.91 to 0.20		not stated; full analysis; R0026074:Results
36	A1	change	0.47 kg				not stated; full analysis; background:basal_bolus_insulin; R0025067:Table 2
36	A1 vs A2	md	0.12 kg		-1.07 to 1.31		not stated; full analysis; background:basal_bolus_insulin; R0025067:Table 2
36	A1	change	0.32 kg				not stated; full analysis; background:basal_insulin; R0025067:Table 2
36	A1 vs A2	md	-0.00 kg		-0.88 to 0.88		not stated; full analysis; background:basal_insulin; R0025067:Table 2
36	A1	change	-0.15 kg				not stated; full analysis; background:premixed_insulin; R0025067:Table 2
36	A2	change	0.52 kg				not stated; full analysis; R0026074:Results
36	A2	change	0.52 kg	0.20		129	not stated; full analysis; registry:outcomes
36	A2	change	0.32 kg				not stated; full analysis; background:basal_insulin; R0025067:Table 2
36	A2	change	0.81 kg				not stated; full analysis; background:premixed_insulin; R0025067:Table 2
36	A2	change	0.35 kg				not stated; full analysis; background:basal_bolus_insulin; R0025067:Table 2

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
36	A1 vs A2	or	21.51	9.43 to 49.11		not stated; full analysis; R0026074:Results
36	A1	responders	58.04		127	not stated; full analysis; R0026074:Results
36	A2	responders	6.04		130	not stated; full analysis; R0026074:Results

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

Arm	Statistic	Estimate	Events / N	Detail
A1	events	33.1	127	while on treatment; safety; R0026074:Results
A1	events		6 / 127	while on treatment; safety; R0026074:Results
A1	events		0 / 127	while on treatment; safety; R0026074:Results
A2	events		11 / 130	while on treatment; safety; R0026074:Results
A2	events	27.7	130	while on treatment; safety; R0026074:Results
A2	events		0 / 130	while on treatment; safety; R0026074:Results

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

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	rate	146		127	while on treatment; safety; R0026074:Results
A1 vs A2	rate ratio	0.94	0.52 to 1.70		while on treatment; safety; R0026074:Results
A2	rate	187		130	while on treatment; safety; R0026074:Results

Systolic blood pressure change (2 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
36	A1	change	-3.12 mmHg			127	not stated; other; R0026074:Supplement Table S3
36	A2	change	2.46 mmHg			130	not stated; other; R0026074:Supplement Table S3

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 127	while on treatment; safety; R0026074:Results
	A2	events				0 / 130	while on treatment; safety; R0026074:Results

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				6 / 127	while on treatment; safety; R0026074:Table 2
	A2	events				4 / 130	while on treatment; safety; R0026074: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 / 127	not stated; randomized; R0026074:Figure 1
	A2	events				1 / 130	not stated; randomized; R0026074:Figure 1

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				14 / 127	while on treatment; safety; R0026074:Table 2
	A2	events				7 / 130	while on treatment; safety; R0026074:Table 2

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				15 / 127	while on treatment; safety; R0026074:Table 2
	A2	events				4 / 130	while on treatment; safety; R0026074:Table 2

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				15 / 127	while on treatment; safety; R0026074:Table 2
	A2	events				2 / 130	while on treatment; safety; R0026074:Table 2

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 127	while on treatment; safety; R0026074:Results
	A2	events				0 / 130	while on treatment; safety; R0026074:Results

Medullary thyroid carcinoma (2 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 127	while on treatment; safety; R0026074:Results
	A2	events				0 / 130	while on treatment; safety; R0026074:Results

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 127	while on treatment; safety; R0026074:Results
	A2	events				0 / 130	while on treatment; safety; R0026074:Results

Diabetic retinopathy complications (2 lines; O33)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 127	while on treatment; safety; diabetic retinopathy; R0026074:Table 2
	A2	events				13 / 130	while on treatment; safety; diabetic retinopathy; R0026074:Table 2

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 127	while on treatment; safety; R0026074:Results
	A2	events				0 / 130	while on treatment; safety; R0026074:Results