parallel randomized trial

LEAD-2

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

Type 2 diabetes (adults)NCT00318461S001502

Design

Randomized: 1,091
Start year: 2006
Treatment: 26 weeks, follow-up 104 weeks
Countries: multinational (170 sites)
Sponsor: Novo Nordisk (industry)
Eligibility: age 18 to 80; HbA1c 7 to 11 percent on one OAD or 7 to 10 on combination; BMI 40 or less; no recent insulin

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 0.6 mg subcutaneous once daily liraglutide 0.6 mg	metformin 1500 to 2000 mg/day; lifestyle: not reported	242	242
A2	Liraglutide 1.2 mg subcutaneous once daily liraglutide 1.2 mg	metformin 1500 to 2000 mg/day; lifestyle: not reported	241	240
A3	Liraglutide 1.8 mg subcutaneous once daily liraglutide 1.8 mg	metformin 1500 to 2000 mg/day; lifestyle: not reported	242	242
A4	Glimepiride glimepiride 4 mg	metformin 1500 to 2000 mg/day; lifestyle: not reported	244	242
A5	Placebo placebo	metformin 1500 to 2000 mg/day; lifestyle: not reported	122	121

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	Glimepiride A4	Placebo A5
age	mean (years)	56	57	57	57	56
age	sd (years)	11	9	9	9	9
asian	n	31	19	18	21	9
asian	percent	13	8	7	9	7
black	n	4	9	5	5	3
black	percent	2	4	2	2	3
bmi	mean (kg/m2)	30.5	31.1	30.9	31.2	31.6
bmi	sd (kg/m2)	4.8	4.8	4.6	4.6	4.4
diabetes duration	mean (years)	7	7	8	8	8
diabetes duration	sd (years)	5	5	5	5	6
female	n	91	111	100	103	49
female	percent	38	46	41	43	40
hba1c	mean (percent)	8.4	8.3	8.4	8.4	8.4
hba1c	sd (percent)	0.9	1.0	1.0	1.0	1.1
other prior oad combination	n	161	150	159	155	81
other prior oad combination	percent	67	62	66	63	66
other race american indian alaska native	n	0	0	0	0	0
other race multiple	n	0	0	0	0	0
other race native hawaiian pacific islander	n	0	0	0	0	0
other race other	percent	2	1	2	1	3
other race unknown	n	5	2	5	2	3
sbp	mean (mmHg)	131	132	131	132	135
sbp	sd (mmHg)	14	14	14	16	16
weight	mean (kg)		88.47	88.02		91.05
weight	sd (kg)		19.06	16.31		17.03
white	n	202	210	214	214	106
white	percent	84	88	88	89	88

Analyses this trial contributes to

Results

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

HbA1c change (24 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-0.7 percent	0.1		239	not stated; modified itt; R0019848:Results
26	A1 vs A5	md	-0.8 percent		-1.0 to -0.6		not stated; modified itt; R0019848:Results
26	A1 vs A4	md	0.29 percent		0.12 to 0.46		not stated; modified itt; registry:outcomes
26	A2 vs A4	md	0.0 percent		-0.2 to 0.2		not stated; modified itt; R0019848:Results
26	A2 vs A5	md	-1.1 percent		-1.3 to -0.9		not stated; modified itt; R0019848:Results
26	A2	change	-1.0 percent	0.1		232	not stated; modified itt; R0019848:Results
26	A3 vs A4	md	-0.0 percent		-0.2 to 0.2		not stated; modified itt; R0019848:Results
26	A3 vs A5	md	-1.1 percent		-1.3 to -0.9		not stated; modified itt; R0019848:Results
26	A3	change	-1.0 percent	0.1		236	not stated; modified itt; R0019848:Results
26	A4	change	-1.0 percent	0.1		234	not stated; modified itt; R0019848:Results
26	A5 vs A4	md	-1.07 percent		-1.28 to -0.86		not stated; modified itt; registry:outcomes
26	A5	change	0.1 percent	0.1		120	not stated; modified itt; R0019848:Results
104	A1 vs A4	md	0.14 percent		-0.06 to 0.34		not stated; modified itt; registry:outcomes
104	A1	change	-0.36 percent	0.08		239	not stated; modified itt; registry:outcomes
104	A1 vs A5	md	-0.61 percent		-0.85 to -0.37		not stated; modified itt; registry:outcomes
104	A2 vs A4	md	-0.07 percent		-0.27 to 0.13		not stated; modified itt; registry:outcomes
104	A2 vs A5	md	-0.81 percent		-1.05 to -0.57		not stated; modified itt; registry:outcomes
104	A2	change	-0.56 percent	0.08		231	not stated; modified itt; registry:outcomes
104	A3 vs A4	md	-0.08 percent		-0.28 to 0.12		not stated; modified itt; registry:outcomes
104	A3 vs A5	md	-0.83 percent		-1.07 to -0.59		not stated; modified itt; registry:outcomes
104	A3	change	-0.58 percent	0.08		235	not stated; modified itt; registry:outcomes
104	A4	change	-0.50 percent	0.08		234	not stated; modified itt; registry:outcomes
104	A5 vs A4	md	-0.75 percent		-0.99 to -0.51		not stated; modified itt; registry:outcomes
104	A5	change	0.25 percent	0.10		120	not stated; modified itt; registry:outcomes

Body weight change in kilograms (diabetes) (22 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.8 kg	0.2		242	not stated; modified itt; R0019848:Results
26	A1 vs A4	md	-2.73 kg		-3.47 to -2.00		not stated; modified itt; registry:outcomes
26	A1 vs A5	md	-0.28 kg		-1.15 to 0.60		not stated; modified itt; registry:outcomes
26	A2	change	-2.6 kg	0.2		236	not stated; modified itt; R0019848:Results
26	A2 vs A4	md	-3.53 kg		-4.27 to -2.79		not stated; modified itt; registry:outcomes
26	A2 vs A5	md	-1.07 kg		-1.94 to -0.19		not stated; modified itt; registry:outcomes
26	A3	change	-2.8 kg	0.2		241	not stated; modified itt; R0019848:Results
26	A3 vs A5	md	-1.29 kg		-2.16 to -0.41		not stated; modified itt; registry:outcomes
26	A3 vs A4	md	-3.75 kg		-4.48 to -3.01		not stated; modified itt; registry:outcomes
26	A4	change	1.0 kg	0.2		237	not stated; modified itt; R0019848:Results
26	A5	change	-1.5 kg	0.3		121	not stated; modified itt; R0019848:Results
104	A1 vs A5	md	-0.27 kg		-1.33 to 0.80		not stated; modified itt; registry:outcomes
104	A1	change	-2.07 kg	0.28		242	not stated; modified itt; registry:outcomes
104	A1 vs A4	md	-2.77 kg		-3.67 to -1.87		not stated; modified itt; registry:outcomes
104	A2	change	-3.03 kg	0.29		236	not stated; modified itt; registry:outcomes
104	A2 vs A4	md	-3.73 kg		-4.64 to -2.83		not stated; modified itt; registry:outcomes
104	A2 vs A5	md	-1.23 kg		-2.30 to -0.16		not stated; modified itt; registry:outcomes
104	A3 vs A4	md	-3.61 kg		-4.51 to -2.72		not stated; modified itt; registry:outcomes
104	A3 vs A5	md	-1.11 kg		-2.18 to -0.05		not stated; modified itt; registry:outcomes
104	A3	change	-2.91 kg	0.28		241	not stated; modified itt; registry:outcomes
104	A4	change	0.70 kg	0.29		237	not stated; modified itt; registry:outcomes
104	A5	change	-1.80 kg	0.38		121	not stated; modified itt; registry:outcomes

HbA1c below 7 percent (5 lines; O03)

Week	Arm	Statistic	Estimate	Events / N	Detail
26	A1	responders	28.0	242	not stated; modified itt; R0019848:Figure 1E
26	A2	responders	35.3	240	not stated; modified itt; R0019848:Figure 1E
26	A3	responders	42.4	242	not stated; modified itt; R0019848:Figure 1E
26	A4	responders	36.3	242	not stated; modified itt; R0019848:Figure 1E
26	A5	responders	10.8	121	not stated; modified itt; R0019848:Figure 1E

Level 2 or 3 hypoglycemia (participants) (15 lines; O04)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		0 / 242	not stated; safety; R0019848:Results
A1	events		0 / 242	not stated; safety; registry:outcomes
A1	events		1 / 242	not stated; safety; registry:adverse_events
A2	events		0 / 240	not stated; safety; R0019848:Results
A2	events		0 / 240	not stated; safety; registry:adverse_events
A3	events		0 / 242	not stated; safety; registry:outcomes
A3	events		0 / 242	not stated; safety; R0019848:Results
A3	events		0 / 242	not stated; safety; registry:adverse_events
A4	events		0 / 242	not stated; safety; R0019848:Results
A4	events		0 / 242	not stated; safety; registry:outcomes
A4	events	17	242	not stated; safety; R0019848:Results
A4	events		0 / 242	not stated; safety; registry:adverse_events
A5	events		0 / 121	not stated; safety; registry:adverse_events
A5	events		0 / 121	not stated; safety; R0019848:Results
A5	events		0 / 121	not stated; safety; registry:outcomes

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	Detail
26	A1	change	-0.6 mmHg	not stated; modified itt; R0019848:Results
26	A2 vs A4	md	-3.2 mmHg	not stated; modified itt; R0019848:Results
26	A3 vs A4	md	-2.7 mmHg	not stated; modified itt; R0019848:Results
26	A4	change	0.4 mmHg	not stated; modified itt; R0019848:Results
26	A5	change	-1.8 mmHg	not stated; modified itt; R0019848:Results

Acute kidney injury (5 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	1 / 242	not stated; safety; Renal failure acute; registry:adverse_events
A2	events	0 / 240	not stated; safety; Renal failure acute; registry:adverse_events
A3	events	0 / 242	not stated; safety; Renal failure acute; registry:adverse_events
A4	events	1 / 242	not stated; safety; Renal failure acute; registry:adverse_events
A5	events	0 / 121	not stated; safety; Renal failure acute; registry:adverse_events

Serious adverse events (5 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	36 / 242	not stated; safety; registry:adverse_events
A2	events	25 / 240	not stated; safety; registry:adverse_events
A3	events	16 / 242	not stated; safety; registry:adverse_events
A4	events	24 / 242	not stated; safety; registry:adverse_events
A5	events	9 / 121	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (10 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	11 / 242	not stated; randomized; R0019848:Table 1
A1	events	11 / 208	not stated; completers; registry:flow
A2	events	8 / 197	not stated; completers; registry:flow
A2	events	23 / 241	not stated; randomized; R0019848:Table 1
A3	events	6 / 191	not stated; completers; registry:flow
A3	events	29 / 242	not stated; randomized; R0019848:Table 1
A4	events	6 / 210	not stated; completers; registry:flow
A4	events	8 / 244	not stated; randomized; R0019848:Table 1
A5	events	2 / 122	not stated; randomized; R0019848:Table 1
A5	events	1 / 74	not stated; completers; registry:flow

Nausea (8 lines; O27A)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	11	242	not stated; safety; R0019848:Results
A1	events		30 / 242	not stated; safety; registry:adverse_events
A2	events		42 / 240	not stated; safety; registry:adverse_events
A2	events	16	240	not stated; safety; R0019848:Results
A3	events	19	242	not stated; safety; R0019848:Results
A3	events		52 / 242	not stated; safety; registry:adverse_events
A4	events		10 / 242	not stated; safety; registry:adverse_events
A5	events		5 / 121	not stated; safety; registry:adverse_events

Vomiting (7 lines; O27B)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		19 / 242	not stated; safety; registry:adverse_events
A2	events		18 / 240	not stated; safety; registry:adverse_events
A3	events		24 / 242	not stated; safety; registry:adverse_events
A4	events	1	242	not stated; safety; R0019848:Results
A4	events		1 / 242	not stated; safety; registry:adverse_events
A5	events		0 / 121	not stated; safety; registry:adverse_events
A5	events	1	121	not stated; safety; R0019848:Results

Diarrhea (10 lines; O27C)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	10	242	not stated; safety; R0019848:Results
A1	events		31 / 242	not stated; safety; registry:adverse_events
A2	events	8	240	not stated; safety; R0019848:Results
A2	events		27 / 240	not stated; safety; registry:adverse_events
A3	events		40 / 242	not stated; safety; registry:adverse_events
A3	events	15	242	not stated; safety; R0019848:Results
A4	events	4	242	not stated; safety; R0019848:Results
A4	events		14 / 242	not stated; safety; registry:adverse_events
A5	events		5 / 121	not stated; safety; registry:adverse_events
A5	events	4	121	not stated; safety; R0019848:Results

Discontinuation due to gastrointestinal adverse events (5 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	3 / 242	not stated; randomized; R0019848:Table 1
A2	events	13 / 241	not stated; randomized; R0019848:Table 1
A3	events	20 / 242	not stated; randomized; R0019848:Table 1
A4	events	0 / 244	not stated; randomized; R0019848:Table 1
A5	events	0 / 122	not stated; randomized; R0019848:Table 1

Acute pancreatitis (12 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 242	not stated; safety; Pancreatitis acute; registry:adverse_events
A1	events	0 / 242	not stated; safety; Pancreatitis; registry:adverse_events
A2	events	1 / 240	not stated; safety; R0019848:Results
A2	events	1 / 240	not stated; safety; Pancreatitis; registry:adverse_events
A2	events	0 / 240	not stated; safety; Pancreatitis acute; registry:adverse_events
A3	events	0 / 242	not stated; safety; Pancreatitis; registry:adverse_events
A3	events	0 / 242	not stated; safety; Pancreatitis acute; registry:adverse_events
A4	events	1 / 242	not stated; safety; Pancreatitis acute; registry:adverse_events
A4	events	0 / 242	not stated; safety; Pancreatitis; registry:adverse_events
A4	events	1 / 242	not stated; safety; R0019848:Results
A5	events	0 / 121	not stated; safety; Pancreatitis; registry:adverse_events
A5	events	0 / 121	not stated; safety; Pancreatitis acute; registry:adverse_events

Thyroid cancer (any) (5 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 242	not stated; safety; registry:adverse_events
A2	events	0 / 240	not stated; safety; registry:adverse_events
A3	events	0 / 242	not stated; safety; registry:adverse_events
A4	events	1 / 242	not stated; safety; registry:adverse_events
A5	events	0 / 121	not stated; safety; registry:adverse_events