parallel randomized trial

LEAD-5

Liraglutide Effect and Action in Diabetes (LEAD-5): Effect on Glycaemic Control After Once Daily Administration of Liraglutide in Combination With Glimepiride and Metformin Versus Glimepiride and Metformin Combination Therapy, and Versus Insulin Glargine Added to Glimepiride and Metformin Combination Therapy in Subjects With Type 2 Diabetes.A Six-month Randomised, Double-blind, Parallel-group, Multi-centre, Multi-national Trial With an Open-label Treat-to-target Insulin Glargine Control Arm.

Type 2 diabetes (adults)NCT00331851S002098

Design

Randomized: 581
Start year: 2006
Treatment: 26 weeks, follow-up 27 weeks
Countries: multinational (107 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 18 to 80; HbA1c 7.5 to 10 on monotherapy or 7 to 10 on combination; BMI 45 or lower

Conduct and analysis

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

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Liraglutide 1.8 mg subcutaneous once daily Liraglutide 1.8 mg	metformin 1 g twice daily and glimepiride 4 mg daily; lifestyle: not reported	232	230
A2	Placebo Placebo	metformin 1 g twice daily and glimepiride 4 mg daily; lifestyle: not reported	115	114
A3	Insulin glargine Insulin glargine	metformin 1 g twice daily and glimepiride 4 mg daily; lifestyle: not reported	234	232

Baseline characteristics

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

Characteristic	Statistic	Liraglutide 1.8 mg subcutaneous once daily A1	Placebo A2	Insulin glargine A3
age	mean (years)	57.6	57.5	57.5
age	sd (years)	9.5	9.6	10.5
bmi	mean (kg/m2)	30.4	31.3	30.3
bmi	sd (kg/m2)	5.3	5.0	5.3
diabetes duration	mean (years)	9.2	9.4	9.7
diabetes duration	sd (years)	5.8	6.2	6.4
female	percent	43	51	40
hba1c	mean (percent)	8.3	8.3	8.2
hba1c	sd (percent)	0.9	0.9	0.9
other fpg	mean (mmol/L)	9.1	9.4	9.1
other fpg	sd (mmol/L)	2.1	2.0	2.0
other prior monotherapy	percent	6	5	5
sbp	mean (mmHg)	135	133	133
sbp	sd (mmHg)	15.0	14.0	14.7
weight	mean (kg)	85.5	85.7	85.0
weight	sd (kg)	19.4	16.7	17.9

Analyses this trial contributes to

Results

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

HbA1c change (11 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.35 percent	0.09		195	not stated; per protocol; R0027336:Supplement Table 1
26	A1	change	-1.33 percent	0.09		230	not stated; modified itt; R0027336:Results
26	A1 vs A2	md	-1.09 percent		-1.28 to -0.90		not stated; modified itt; R0027336:Results
26	A1 vs A2	md	-1.00 percent		-1.19 to -0.80		not stated; per protocol; R0027336:Supplement Table 1
26	A1 vs A3	md	-0.24 percent		-0.39 to -0.08		not stated; modified itt; R0027336:Results
26	A1 vs A3	md	-0.25 percent		-0.40 to -0.09		not stated; per protocol; R0027336:Supplement Table 1
26	A2	change	-0.24 percent	0.11		114	not stated; modified itt; R0027336:Results
26	A2	change	-0.35 percent	0.11		90	not stated; per protocol; R0027336:Supplement Table 1
26	A3	change	-1.09 percent	0.09		232	not stated; modified itt; R0027336:Results
26	A3	change	-1.10 percent	0.09		205	not stated; per protocol; R0027336:Supplement Table 1
26	A3 vs A2	md	-0.85 percent		-1.04 to -0.66		not stated; modified itt; R0027336:Results

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A2	md	-1.39 kg		-2.10 to -0.69		not stated; modified itt; R0027336:Results
26	A1	change	-1.8 kg	0.33		230	not stated; modified itt; R0027336:Results
26	A1 vs A3	md	-3.43 kg		-4.00 to -2.86		not stated; modified itt; R0027336:Results
26	A2	change	-0.42 kg	0.39		114	not stated; modified itt; R0027336:Results
26	A3	change	1.6 kg	0.33		232	not stated; modified itt; R0027336:Results

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

Arm	Statistic	Estimate	Events / N	Detail
A1	events		5 / 230	not stated; safety; R0027336:Results
A1	events	27.4	230	not stated; safety; R0027336:Results
A2	events		0 / 114	not stated; safety; R0027336:Results
A2	events	16.7	114	not stated; safety; R0027336:Results
A3	events		0 / 232	not stated; safety; R0027336:Results
A3	events	28.9	232	not stated; safety; R0027336:Results

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	change	-4.0 mmHg		230	not stated; modified itt; R0027336:Results
26	A1 vs A2	md	-2.53 mmHg	-5.36 to 0.29		not stated; modified itt; R0027336:Results
26	A1 vs A3	md	-4.51 mmHg	-6.82 to -2.20		not stated; modified itt; R0027336:Results
26	A2	change	-1.4 mmHg		114	not stated; modified itt; R0027336:Results
26	A3	change	0.54 mmHg		232	not stated; modified itt; R0027336:Results

Serious adverse events (3 lines; O25)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	4	230	not stated; safety; R0027336:Results
A2	events	7	114	not stated; safety; R0027336:Results
A3	events	7	232	not stated; safety; R0027336:Results

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	11 / 230	not stated; modified itt; R0027336:Figure 1
A2	events	1 / 114	not stated; modified itt; R0027336:Figure 1
A3	events	5 / 232	not stated; modified itt; R0027336:Figure 1

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	32 / 230	not stated; safety; R0027336:Supplement Table 2
A2	events	4 / 114	not stated; safety; R0027336:Supplement Table 2
A3	events	3 / 232	not stated; safety; R0027336:Supplement Table 2

Vomiting (3 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	15 / 230	not stated; safety; R0027336:Supplement Table 2
A2	events	4 / 114	not stated; safety; R0027336:Supplement Table 2
A3	events	1 / 232	not stated; safety; R0027336:Supplement Table 2

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	23 / 230	not stated; safety; R0027336:Supplement Table 2
A2	events	6 / 114	not stated; safety; R0027336:Supplement Table 2
A3	events	3 / 232	not stated; safety; R0027336:Supplement Table 2

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				5 / 230	not stated; safety; R0027336:Supplement Table 2
	A3	events				2 / 232	not stated; safety; R0027336:Supplement Table 2

Acute pancreatitis (3 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 230	not stated; safety; R0027336:Results
A2	events	0 / 114	not stated; safety; R0027336:Results
A3	events	0 / 232	not stated; safety; R0027336:Results

Diabetic retinopathy complications (3 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	2 / 230	not stated; safety; diabetic retinopathy; R0027336:Supplement Table 2
A2	events	3 / 114	not stated; safety; diabetic retinopathy; R0027336:Supplement Table 2
A3	events	4 / 232	not stated; safety; diabetic retinopathy; R0027336:Supplement Table 2