parallel randomized trial

LEAD-4

Effect on Glycemic Control of Liraglutide in Combination With Rosiglitazone Plus Metformin Versus Rosiglitazone Plus Metformin in Subjects With Type 2 Diabetes

Type 2 diabetes (adults)NCT00333151S002222

Design

Randomized: 533
Start year: 2006
Treatment: 26 weeks, follow-up 26 weeks
Countries: USA, Canada (96 sites)
Sponsor: Novo Nordisk (industry)
Eligibility: age 18 to 80; HbA1c 7 to 11 percent on OAD monotherapy or 7 to 10 on combination; BMI 45 or less

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: modified itt
Missing data: LOCF

Arms

Arm	Treatment	Background	Randomized
A1	Liraglutide 1.2 mg subcutaneous once daily Liraglutide 1.2 mg plus metformin and rosiglitazone	metformin 2000 mg and rosiglitazone 8 mg; lifestyle: not reported	178
A2	Liraglutide 1.8 mg subcutaneous once daily Liraglutide 1.8 mg plus metformin and rosiglitazone	metformin 2000 mg and rosiglitazone 8 mg; lifestyle: not reported	178
A3	Placebo Placebo plus metformin and rosiglitazone	metformin 2000 mg and rosiglitazone 8 mg; lifestyle: not reported	177

Baseline characteristics

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

Characteristic	Statistic	Liraglutide 1.2 mg subcutaneous once daily A1	Liraglutide 1.8 mg subcutaneous once daily A2	Placebo A3
age	mean (years)	55	55	55
age	sd (years)	10	11	10
asian	percent	1	3	2
black	percent	15	10	10
bmi	mean (kg/m2)	33.2	33.5	33.9
bmi	sd (kg/m2)	5.4	5.1	5.2
diabetes duration	mean (years)	9	9	9
diabetes duration	sd (years)	6	6	6
female	percent	43	49	38
hba1c	mean (percent)	8.5	8.6	8.4
hba1c	sd (percent)	1.2	1.2	1.2
hispanic	percent	13	16	16
other race american indian alaska native	percent	1	1	1
other race other	percent	2	3	3
sbp	mean (mmHg)	129	126	128
sbp	sd (mmHg)	14.8	14.2	14.5
weight	mean (kg)	95.34	94.94	98.52
weight	sd (kg)	18.35	19.15	18.19
white	percent	81	83	84

Results

50 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	Detail
26	A1	change	-1.5 percent	0.1		not stated; modified itt; R0017606:Results
26	A1 vs A3	md	-0.9 percent		-1.1 to -0.8	not stated; modified itt; R0017606:Results
26	A2	change	-1.5 percent	0.1		not stated; modified itt; R0017606:Results
26	A2 vs A3	md	-1.1 percent		-1.1 to -0.8	not stated; modified itt; R0017606:Results
26	A3	change	-0.5 percent	0.1		not stated; modified itt; R0017606:Results

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

Week	Arm	Statistic	Estimate	SE or SD	Detail
26	A1	change	-1.0 kg	0.3	not stated; modified itt; R0017606:Results
26	A2	change	-2.0 kg	0.3	not stated; modified itt; R0017606:Results
26	A3	change	0.6 kg	0.3	not stated; modified itt; R0017606:Results

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Estimate	Detail
26	A1	responders	57.5	not stated; modified itt; R0017606:Results
26	A2	responders	53.7	not stated; modified itt; R0017606:Results
26	A3	responders	28.1	not stated; modified itt; R0017606:Results

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

Arm	Statistic	Estimate	Events / N	Detail
A1	events	9.0		not stated; safety; R0017606:Results
A1	events		0 /	not stated; safety; R0017606:Results
A2	events	7.9		not stated; safety; R0017606:Results
A2	events		0 /	not stated; safety; R0017606:Results
A3	events		0 /	not stated; safety; R0017606:Results
A3	events	5.1		not stated; safety; R0017606:Results

Level 2 or 3 hypoglycemia (episode rate) (6 lines; O04B)

Arm	Statistic	Estimate	Detail
A1	rate		not stated; safety; R0017606:Results
A1	rate	0.4	not stated; safety; R0017606:Results
A2	rate		not stated; safety; R0017606:Results
A2	rate	0.6	not stated; safety; R0017606:Results
A3	rate	0.2	not stated; safety; R0017606:Results
A3	rate		not stated; safety; R0017606:Results

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Detail
26	A1 vs A3	md	-5.6 mmHg		not stated; modified itt; R0017606:Results
26	A1	change	-6.7 mmHg	1.1	not stated; modified itt; R0017606:Table 2
26	A2	change	-5.6 mmHg	1.1	not stated; modified itt; R0017606:Table 2
26	A2 vs A3	md	-4.5 mmHg		not stated; modified itt; R0017606:Results
26	A3	change	-1.1 mmHg	1.2	not stated; modified itt; R0017606:Table 2

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 178	not stated; randomized; R0017606:Results
A2	events	0 / 178	not stated; randomized; R0017606:Results
A3	events	0 / 177	not stated; randomized; R0017606:Results

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	8 / 178	not stated; randomized; R0017606:Results
A2	events	7 / 178	not stated; randomized; R0017606:Results
A3	events	12 / 177	not stated; randomized; R0017606:Results

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	11 / 178	not stated; randomized; R0017606:Table 1
A2	events	27 / 178	not stated; randomized; R0017606:Table 1
A3	events	6 / 177	not stated; randomized; R0017606:Table 1

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events	29				not stated; safety; R0017606:Results
	A2	events	40				not stated; safety; R0017606:Results

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events	7				not stated; safety; R0017606:Results
	A2	events	17				not stated; safety; R0017606:Results

Discontinuation due to gastrointestinal adverse events (3 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	5 / 178	not stated; randomized; R0017606:Table 1
A2	events	19 / 178	not stated; randomized; R0017606:Table 1
A3	events	0 / 177	not stated; randomized; R0017606:Table 1

Acute pancreatitis (3 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 178	not stated; randomized; pancreatitis; R0017606:Results
A2	events	0 / 178	not stated; randomized; pancreatitis; R0017606:Results
A3	events	0 / 177	not stated; randomized; pancreatitis; R0017606:Results

Death by suicide (3 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 178	not stated; randomized; R0017606:Results
A2	events	0 / 178	not stated; randomized; R0017606:Results
A3	events	0 / 177	not stated; randomized; R0017606:Results