parallel randomized trial

LEAD-1

Liraglutide Effect and Action in Diabetes (LEAD-1): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Glimepiride Versus Glimepiride Monotherapy Versus Glimepiride and Rosiglitazone Combination Therapy in Subjects With Type 2 Diabetes.

Type 2 diabetes (adults)NCT00318422S001584

Design

Randomized: 1,041
Start year: 2006
Treatment: 26 weeks, follow-up 26 weeks
Countries: multinational (116 sites)
Sponsor: Novo Nordisk (industry)
Eligibility: age 18 to 80; HbA1c 7.0 to 11.0 (mono) or 7.0 to 10.0 (combination); BMI up to 45

Conduct and analysis

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

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Liraglutide 0.6 mg subcutaneous once daily Liraglutide 0.6 mg plus glimepiride	glimepiride 2 to 4 mg daily; lifestyle: not reported	233
A2	Liraglutide 1.2 mg subcutaneous once daily Liraglutide 1.2 mg plus glimepiride	glimepiride 2 to 4 mg daily; rosiglitazone placebo; lifestyle: not reported	228	228
A3	Liraglutide 1.8 mg subcutaneous once daily Liraglutide 1.8 mg plus glimepiride	glimepiride 2 to 4 mg daily; rosiglitazone placebo; lifestyle: not reported	234	234
A4	Placebo Placebo plus glimepiride	glimepiride 2 to 4 mg daily; lifestyle: not reported	114	114
A5	Rosiglitazone Rosiglitazone 4 mg plus glimepiride	glimepiride 2 to 4 mg daily; lifestyle: not reported	232

Baseline characteristics

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

Characteristic	Statistic	Liraglutide 0.6 mg subcutaneous once daily A1	Liraglutide 1.2 mg subcutaneous once daily A2	Liraglutide 1.8 mg subcutaneous once daily A3	Placebo A4	Rosiglitazone A5
age	mean (years)	55.7	57.7	55.6	54.7	56.0
age	sd (years)	9.9	9.0	10.0	10.0	9.8
black	n		7	9	1
bmi	mean (kg/m2)	30.0	29.8	30.0	30.3	29.4
bmi	sd (kg/m2)	5.0	5.1	5.1	5.4	4.8
diabetes duration	median (years)	6.5	6.7	6.5	6.5	6.6
diabetes duration	q1 (years)	4.0	4.0	3.7	4.5	4.3
diabetes duration	q3 (years)	10.2	10.7	10.5	10.6	10.7
female	percent	46	55	47	53	53
hba1c	mean (percent)	8.4	8.5	8.5	8.4	8.4
hba1c	sd (percent)	1.0	1.1	0.9	1.0	1.0
other diabetic retinopathy	percent	17.2	14.9	12.0	13.2	16.4
other fpg	mean (mmol/L)	10.0	9.8	9.7	9.5	9.9
other fpg	sd (mmol/L)	2.4	2.7	2.4	2.0	2.5
other hypertension	percent	69.1	68.0	69.7	64.9	66.8
other prior ogla monotherapy	percent	30	31	27	32	32
sbp	mean (mmHg)	131	133	132	131	133
sbp	sd (mmHg)	16	15	16	15.3	15
weight	mean (kg)	82.6	80.0	83.0	81.9	80.6
weight	sd (kg)	17.7	17.1	18.1	17.1	17.0

Analyses this trial contributes to

Results

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

HbA1c change (9 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Detail
26	A1	change	-0.6 percent		not stated; modified itt; R0026073:Abstract
26	A1 vs A4	md	-0.8 percent	-1.1 to -0.6	not stated; modified itt; R0026073:Results
26	A2	change	-1.1 percent		not stated; modified itt; R0026073:Results
26	A2 vs A4	md	-1.3 percent	-1.5 to -1.1	not stated; modified itt; R0026073:Results
26	A3	change	-1.1 percent		not stated; modified itt; R0026073:Results
26	A3 vs A4	md	-1.4 percent	-1.6 to -1.1	not stated; modified itt; R0026073:Results
26	A4	change	0.2 percent		not stated; modified itt; R0026073:Results
26	A5	change	-0.4 percent		not stated; modified itt; R0026073:Results
26	A5 vs A4	md	-0.7 percent	-0.9 to -0.4	not stated; modified itt; R0026073:Results

Body weight change in kilograms (diabetes) (5 lines; O02)

Week	Arm	Statistic	Estimate	Detail
26	A1	change	0.7 kg	not stated; modified itt; R0026073:Results
26	A2	change	0.3 kg	not stated; modified itt; R0026073:Results
26	A3	change	-0.2 kg	not stated; modified itt; R0026073:Results
26	A4	change	-0.1 kg	not stated; modified itt; R0026073:Results
26	A5	change	2.1 kg	not stated; modified itt; R0026073:Results

HbA1c below 7 percent (2 lines; O03)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A3	responders	42				not stated; modified itt; R0026073:Results
26	A4	responders	8				not stated; modified itt; R0026073:Results

Level 2 or 3 hypoglycemia (participants) (10 lines; O04)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	5.2		not stated; modified itt; R0026073:Results
A1	events		0 /	not stated; modified itt; R0026073:Results
A2	events	9.2		not stated; modified itt; R0026073:Results
A2	events		0 /	not stated; modified itt; R0026073:Results
A3	events		1 /	not stated; modified itt; R0026073:Results
A3	events	8.1		not stated; modified itt; R0026073:Results
A4	events	2.6		not stated; modified itt; R0026073:Results
A4	events		0 /	not stated; modified itt; R0026073:Results
A5	events	4.3		not stated; modified itt; R0026073:Results
A5	events		0 /	not stated; modified itt; R0026073:Results

All cause mortality (5 lines; O20)

Arm	Statistic	Detail
A1	events	not stated; modified itt; R0026073:Results
A2	events	not stated; modified itt; R0026073:Results
A3	events	not stated; modified itt; R0026073:Results
A4	events	not stated; modified itt; R0026073:Results
A5	events	not stated; modified itt; R0026073:Results

Serious adverse events (5 lines; O25)

Arm	Statistic	Estimate	Detail
A1	events	3	not stated; modified itt; R0026073:Results
A2	events	4	not stated; modified itt; R0026073:Results
A3	events	5	not stated; modified itt; R0026073:Results
A4	events	3	not stated; modified itt; R0026073:Results
A5	events	3	not stated; modified itt; R0026073:Results

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	events	10.5				not stated; modified itt; R0026073:Results
	A4	events	1.8				not stated; modified itt; R0026073:Results

Vomiting (1 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	events	4.4				not stated; modified itt; R0026073:Results

Diarrhea (1 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	events	7.9				not stated; modified itt; R0026073:Results