parallel randomized trial

LEAD-3

Liraglutide Effect and Action in Diabetes (LEAD-3): Effect on Glycemic Control of Liraglutide Versus Glimepiride in Type 2 Diabetes

Type 2 diabetes (adults)NCT00294723S001094

Design

Randomized: 746
Start year: 2006
Treatment: 104 weeks, follow-up 195 weeks
Countries: United States, Mexico
Sponsor: Novo Nordisk (industry)
Eligibility: age 18 to 80; BMI 45 or less; HbA1c 7 to 11 percent on diet or 7 to 10 percent on OAD monotherapy

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 1.2 mg subcutaneous once daily Liraglutide 1.2 mg	none; lifestyle: not reported	251	251
A2	Liraglutide 1.8 mg subcutaneous once daily Liraglutide 1.8 mg	none; lifestyle: not reported	247	246
A3	Glimepiride Glimepiride 8 mg	none; lifestyle: not reported	248	248

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	Glimepiride A3
age: 18 or less	n	0	0	0
age: 18 to 65	n	208	222	208
age: 65 or older	n	43	25	40
age	mean (years)	53.7	52.0	53.4
age	sd (years)	11.0	10.8	10.9
asian	n	5	12	9
asian	percent	2	5	4
black	n	34	30	30
black	percent	14	12	12
bmi	mean (kg/m2)	33.2	32.8	33.2
bmi	sd (kg/m2)	5.6	6.3	5.6
diabetes duration	mean (years)	5.2	5.3	5.6
diabetes duration	sd (years)	5.5	5.1	5.1
female	n	134	126	115
hba1c	mean (percent)	8.2	8.2	8.2
hba1c	sd (percent)	1.1	1.1	1.1
hispanic	n	81	87	93
hispanic	percent	32	35	38
other race american indian alaska native	n	0	0	0
other race multiple	n	0	0	0
other race native hawaiian pacific islander	n	0	2	0
other race other	n	12	19	17
other race other	percent	5	8	7
sbp	mean (mmHg)	127.6	128.0	130.0
sbp	sd (mmHg)	14.3	13.9	16.1
weight	mean (kg)	92.1	92.6	93.3
weight	sd (kg)	19.0	20.8	19.0
white	n	200	186	192
white	percent	80	75	77

Results

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

HbA1c change (41 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-0.84 percent	0.08		236	not stated; modified itt; R0025474:Table 2
52	A1 vs A3	md	-0.33 percent		-0.53 to -0.13		not stated; modified itt; R0025474:Table 2
52	A1	final	7.5 percent	0.09			not stated; other; R0025474:Table 2
52	A2	change	-1.14 percent	0.08		234	not stated; modified itt; R0025474:Table 2
52	A2	final	7.2 percent	0.08			not stated; other; R0025474:Table 2
52	A2 vs A3	md	-0.62 percent		-0.83 to -0.42		not stated; modified itt; R0025474:Table 2
52	A2 vs A1	md	-0.29 percent		-0.50 to -0.09		not stated; modified itt; R0025474:Table 2
52	A3	final	7.8 percent	0.08			not stated; other; R0025474:Table 2
52	A3	change	-0.51 percent	0.08		241	not stated; modified itt; R0025474:Table 2
104	A1	final	7.5 percent				not stated; modified itt; R0024257:Figure 2C
104	A1	final	7.1 percent			110	not stated; completers; R0024257:Figure 2A
104	A1	final	7.1 percent				not stated; modified itt; R0024257:Figure 2B
104	A1 vs A3	md	-0.31 percent		-0.54 to -0.08		not stated; modified itt; R0024257:Table 2
104	A1 vs A3	md	-0.37 percent		-0.71 to -0.02		not stated; completers; R0024257:Results
104	A1	change	-0.9 percent			110	not stated; completers; R0024257:Results
104	A1	change	-0.59 percent	0.09		236	not stated; modified itt; registry:outcomes
104	A1	change	-0.6 percent				not stated; modified itt; R0024257:Table 2
104	A1	final	6.8 percent				not stated; completers; background:prior_diet_exercise; R0024257:Figure 2D
104	A2	change	-0.88 percent	0.09		234	not stated; modified itt; registry:outcomes
104	A2	change	-1.1 percent			114	not stated; completers; R0024257:Results
104	A2	final	7.2 percent				not stated; modified itt; R0024257:Figure 2C
104	A2	final	6.9 percent			114	not stated; completers; R0024257:Figure 2A
104	A2	final	6.9 percent				not stated; modified itt; R0024257:Figure 2B
104	A2 vs A1	md	-0.29 percent		-0.52 to -0.06		not stated; modified itt; registry:outcomes
104	A2 vs A3	md	-0.60 percent		-0.83 to -0.38		not stated; modified itt; R0024257:Table 2
104	A2 vs A3	md	-0.55 percent		-0.88 to -0.21		not stated; completers; R0024257:Results
104	A2	final	6.7 percent				not stated; completers; background:prior_diet_exercise; R0024257:Figure 2D
104	A2	change	-0.9 percent				not stated; modified itt; R0024257:Table 2
104	A3	final	7.3 percent				not stated; completers; background:prior_diet_exercise; R0024257:Figure 2D
104	A3	final	7.5 percent				not stated; modified itt; R0024257:Figure 2B
104	A3	final	7.5 percent			97	not stated; completers; R0024257:Figure 2A
104	A3	final	7.8 percent				not stated; modified itt; R0024257:Figure 2C
104	A3	change	-0.6 percent			97	not stated; completers; R0024257:Results
104	A3	change	-0.28 percent	0.09		241	not stated; modified itt; registry:outcomes
104	A3	change	-0.3 percent				not stated; modified itt; R0024257:Table 2
156	A1 vs A3	md	-0.28 percent		-0.49 to -0.06		not stated; modified itt; registry:outcomes
156	A1	change	-0.44 percent	0.09		236	not stated; modified itt; registry:outcomes
156	A2 vs A1	md	-0.28 percent		-0.49 to -0.06		not stated; modified itt; registry:outcomes
156	A2	change	-0.71 percent	0.09		234	not stated; modified itt; registry:outcomes
156	A2 vs A3	md	-0.55 percent		-0.77 to -0.34		not stated; modified itt; registry:outcomes
156	A3	change	-0.16 percent	0.08		241	not stated; modified itt; registry:outcomes

Body weight change in kilograms (diabetes) (31 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-2.05 kg	0.28		245	not stated; modified itt; R0025474:Table 2
52	A1 vs A3	md	-3.17 kg		-3.87 to -2.47		not stated; modified itt; R0025474:Table 2
52	A1	final	90.2 kg	1.22			not stated; other; R0025474:Table 2
52	A2 vs A1	md	-0.41 kg		-1.11 to 0.30		not stated; modified itt; registry:outcomes
52	A2 vs A3	md	-3.52 kg		-4.28 to -2.87		not stated; modified itt; R0025474:Table 2
52	A2 vs A3	md	-3.58 kg		-4.28 to -2.87		not stated; modified itt; registry:outcomes
52	A2	change	-2.45 kg	0.28		240	not stated; modified itt; R0025474:Table 2
52	A2	final	90.5 kg	1.31			not stated; other; R0025474:Table 2
52	A2 vs A1	md	-4.06 kg		-1.11 to 0.30		not stated; modified itt; R0025474:Table 2
52	A3	final	94.4 kg	1.23			not stated; other; R0025474:Table 2
52	A3	change	1.12 kg	0.27		248	not stated; modified itt; R0025474:Table 2
104	A1	change	-1.89 kg	0.31		245	not stated; modified itt; registry:outcomes
104	A1 vs A3	md	-2.84 kg		-3.63 to -2.06		not stated; modified itt; R0024257:Table 2
104	A1	change	-1.89 kg				not stated; modified itt; R0024257:Table 2
104	A1	change	-2.1 kg			110	not stated; completers; R0024257:Figure 3E
104	A1 vs A3	md	-3.24 kg		-4.49 to -1.99		not stated; completers; R0024257:Figure 3E
104	A2 vs A1	md	-0.80 kg		-1.59 to -0.01		not stated; modified itt; registry:outcomes
104	A2 vs A3	md	-3.78 kg		-5.02 to -2.54		not stated; completers; R0024257:Figure 3E
104	A2	change	-2.70 kg				not stated; modified itt; R0024257:Table 2
104	A2	change	-2.70 kg	0.32		240	not stated; modified itt; registry:outcomes
104	A2	change	-2.7 kg			114	not stated; completers; R0024257:Figure 3E
104	A2 vs A3	md	-3.65 kg		-4.44 to -2.86		not stated; modified itt; R0024257:Table 2
104	A3	change	0.95 kg				not stated; modified itt; R0024257:Table 2
104	A3	change	1.1 kg			97	not stated; completers; R0024257:Figure 3E
104	A3	change	0.95 kg	0.30		248	not stated; modified itt; registry:outcomes
156	A1 vs A3	md	-2.72 kg		-3.52 to -1.93		not stated; modified itt; registry:outcomes
156	A1	change	-1.68 kg	0.32		245	not stated; modified itt; registry:outcomes
156	A2 vs A3	md	-3.48 kg		-4.28 to -2.68		not stated; modified itt; registry:outcomes
156	A2	change	-2.43 kg	0.32		240	not stated; modified itt; registry:outcomes
156	A2 vs A1	md	-0.75 kg		-1.55 to 0.05		not stated; modified itt; registry:outcomes
156	A3	change	1.05 kg	0.31		248	not stated; modified itt; registry:outcomes

HbA1c below 7 percent (8 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
104	A1	responders	36.9		251	not stated; modified itt; R0024257:Table 2
104	A1	responders	53		110	not stated; completers; R0024257:Figure 3A
104	A1 vs A3	or	1.98	1.30 to 3.00		not stated; modified itt; R0024257:Table 2
104	A2	responders	44.4		246	not stated; modified itt; R0024257:Table 2
104	A2	responders	58		114	not stated; completers; R0024257:Figure 3A
104	A2 vs A3	or	2.81	1.85 to 4.26		not stated; modified itt; R0024257:Table 2
104	A3	responders	23.2		248	not stated; modified itt; R0024257:Table 2
104	A3	responders	37		97	not stated; completers; R0024257:Figure 3A

Level 2 or 3 hypoglycemia (participants) (18 lines; O04)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		0 /	not stated; other; R0025474:Results
A1	events	12	251	not stated; safety; R0024257:Results
A1	events		0 / 251	not stated; safety; R0024257:Results
A1	events		0 / 53	not stated; other; registry:outcomes
A1	events		0 / 251	not stated; safety; registry:adverse_events
A1	events		0 / 53	not stated; other; registry:adverse_events
A2	events		0 /	not stated; other; R0025474:Results
A2	events		1 / 246	not stated; safety; registry:adverse_events
A2	events	10	246	not stated; safety; R0024257:Results
A2	events		1 / 246	not stated; safety; R0024257:Results
A2	events		0 / 62	not stated; other; registry:adverse_events
A2	events		0 / 62	not stated; other; registry:outcomes
A3	events		1 / 28	not stated; other; registry:adverse_events
A3	events		1 / 28	not stated; other; registry:outcomes
A3	events	26	248	not stated; safety; R0024257:Results
A3	events		0 /	not stated; other; R0025474:Results
A3	events		0 / 248	not stated; safety; R0024257:Results
A3	events		0 / 248	not stated; safety; registry:adverse_events

Level 2 or 3 hypoglycemia (episode rate) (21 lines; O04B)

Arm	Statistic	Estimate	95% CI	Detail
A1	rate			not stated; other; registry:outcomes
A1	rate	0.21		not stated; safety; R0024257:Results
A1	rate			not stated; safety; registry:outcomes
A1	rate			not stated; other; registry:outcomes
A1	rate	0.30		not stated; other; R0025474:Table 2
A1 vs A3	rate ratio	0.16	0.08 to 0.32	not stated; other; R0025474:Table 2
A1	rate			not stated; safety; registry:outcomes
A2	rate			not stated; other; registry:outcomes
A2 vs A1	rate ratio	0.62	0.29 to 1.30	not stated; other; R0025474:Table 2
A2 vs A3	rate ratio	0.10	0.05 to 0.20	not stated; other; R0025474:Table 2
A2	rate			not stated; other; registry:outcomes
A2	rate			not stated; safety; registry:outcomes
A2	rate			not stated; safety; registry:outcomes
A2	rate	0.22		not stated; safety; R0024257:Results
A2	rate	0.25		not stated; other; R0025474:Table 2
A3	rate			not stated; other; registry:outcomes
A3	rate			not stated; safety; registry:outcomes
A3	rate			not stated; other; registry:outcomes
A3	rate	1.96		not stated; other; R0025474:Table 2
A3	rate			not stated; safety; registry:outcomes
A3	rate	1.75		not stated; safety; R0024257:Results

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Detail
104	A1	change	-1.35 mmHg		not stated; modified itt; R0024257:Table 2
104	A1 vs A3	md	-0.86 mmHg	-3.18 to 1.46	not stated; modified itt; R0024257:Table 2
104	A2 vs A3	md	-1.88 mmHg	-4.21 to 0.45	not stated; modified itt; R0024257:Table 2
104	A2	change	-2.37 mmHg		not stated; modified itt; R0024257:Table 2
104	A3	change	-0.49 mmHg		not stated; modified itt; R0024257:Table 2

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 149	not stated; other; R0024257:Results
A2	events	1 / 154	not stated; other; R0024257:Results
A3	events	0 / 137	not stated; other; R0024257:Results

Hospitalization for heart failure (6 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	1 / 251	not stated; safety; cardiac failure congestive; registry:adverse_events
A1	events	0 / 53	not stated; other; cardiac failure congestive; registry:adverse_events
A2	events	0 / 62	not stated; other; cardiac failure congestive; registry:adverse_events
A2	events	0 / 246	not stated; safety; cardiac failure congestive; registry:adverse_events
A3	events	0 / 248	not stated; safety; cardiac failure congestive; registry:adverse_events
A3	events	0 / 28	not stated; other; cardiac failure congestive; registry:adverse_events

Health related quality of life total score (any instrument) (3 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
52	A1	final	453.8 points	2.6	245	not stated; other; R0025474:Table 3
52	A2	final	462.3 points	2.6	242	not stated; other; R0025474:Table 3
52	A3	final	451.7 points	2.6	245	not stated; other; R0025474:Table 3

Serious adverse events (6 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	1 / 53	not stated; other; registry:adverse_events
A1	events	23 / 251	not stated; safety; R0024257:Results
A2	events	5 / 62	not stated; other; registry:adverse_events
A2	events	22 / 246	not stated; safety; R0024257:Results
A3	events	2 / 28	not stated; other; registry:adverse_events
A3	events	20 / 248	not stated; safety; R0024257:Results

Discontinuation due to adverse events (9 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	5 / 149	not stated; other; R0024257:Figure 1
A1	events	1 / 53	not stated; other; registry:flow
A1	events	25 / 251	not stated; safety; R0024257:Figure 1
A2	events	18 / 246	not stated; safety; R0024257:Figure 1
A2	events	5 / 154	not stated; other; R0024257:Figure 1
A2	events	1 / 62	not stated; other; registry:flow
A3	events	2 / 137	not stated; other; R0024257:Figure 1
A3	events	15 / 248	not stated; safety; R0024257:Figure 1
A3	events	0 / 28	not stated; other; registry:flow

Nausea (6 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 53	not stated; other; registry:adverse_events
A1	events	72 / 251	not stated; safety; R0024257:Table 3
A2	events	75 / 246	not stated; safety; R0024257:Table 3
A2	events	0 / 62	not stated; other; registry:adverse_events
A3	events	0 / 28	not stated; other; registry:adverse_events
A3	events	21 / 248	not stated; safety; R0024257:Table 3

Vomiting (6 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 53	not stated; other; registry:adverse_events
A1	events	33 / 251	not stated; safety; R0024257:Table 3
A2	events	25 / 246	not stated; safety; R0024257:Table 3
A2	events	0 / 62	not stated; other; registry:adverse_events
A3	events	0 / 28	not stated; other; registry:adverse_events
A3	events	10 / 248	not stated; safety; R0024257:Table 3

Diarrhea (12 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	44 / 251	not stated; safety; R0024257:Table 3
A1	events	0 / 251	not stated; safety; registry:adverse_events
A1	events	3 / 53	not stated; other; registry:adverse_events
A1	events	0 / 53	not stated; other; registry:adverse_events
A2	events	0 / 246	not stated; safety; registry:adverse_events
A2	events	5 / 62	not stated; other; registry:adverse_events
A2	events	0 / 62	not stated; other; registry:adverse_events
A2	events	48 / 246	not stated; safety; R0024257:Table 3
A3	events	0 / 28	not stated; other; registry:adverse_events
A3	events	23 / 248	not stated; safety; R0024257:Table 3
A3	events	1 / 28	not stated; other; registry:adverse_events
A3	events	1 / 248	not stated; safety; registry:adverse_events

Constipation (6 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	21 / 251	not stated; safety; R0024257:Table 3
A1	events	0 / 53	not stated; other; registry:adverse_events
A2	events	0 / 62	not stated; other; registry:adverse_events
A2	events	29 / 246	not stated; safety; R0024257:Table 3
A3	events	12 / 248	not stated; safety; R0024257:Table 3
A3	events	0 / 28	not stated; other; registry:adverse_events

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 149	not stated; other; nausea; R0024257:Results
A2	events	0 / 154	not stated; other; nausea; R0024257:Results
A3	events	0 / 137	not stated; other; nausea; R0024257:Results

Gallbladder and biliary disease (12 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 251	not stated; safety; cholelithiasis; registry:adverse_events
A1	events	1 / 251	not stated; safety; cholecystitis; registry:adverse_events
A1	events	0 / 53	not stated; other; cholecystitis; registry:adverse_events
A1	events	0 / 53	not stated; other; cholelithiasis; registry:adverse_events
A2	events	0 / 246	not stated; safety; cholecystitis; registry:adverse_events
A2	events	0 / 62	not stated; other; cholecystitis; registry:adverse_events
A2	events	0 / 62	not stated; other; cholelithiasis; registry:adverse_events
A2	events	1 / 246	not stated; safety; cholelithiasis; registry:adverse_events
A3	events	0 / 28	not stated; other; cholelithiasis; registry:adverse_events
A3	events	0 / 28	not stated; other; cholecystitis; registry:adverse_events
A3	events	0 / 248	not stated; safety; cholelithiasis; registry:adverse_events
A3	events	0 / 248	not stated; safety; cholecystitis; registry:adverse_events

Acute pancreatitis (18 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 251	not stated; safety; registry:adverse_events
A1	events	0 / 251	not stated; safety; oedematous pancreatitis; registry:adverse_events
A1	events	1 / 251	not stated; safety; pancreatitis; registry:adverse_events
A1	events	0 / 53	not stated; other; pancreatitis; registry:adverse_events
A1	events	0 / 53	not stated; other; registry:adverse_events
A1	events	0 / 53	not stated; other; oedematous pancreatitis; registry:adverse_events
A2	events	0 / 246	not stated; safety; pancreatitis; registry:adverse_events
A2	events	1 / 246	not stated; safety; registry:adverse_events
A2	events	1 / 246	not stated; safety; oedematous pancreatitis; registry:adverse_events
A2	events	0 / 62	not stated; other; registry:adverse_events
A2	events	0 / 62	not stated; other; oedematous pancreatitis; registry:adverse_events
A2	events	0 / 62	not stated; other; pancreatitis; registry:adverse_events
A3	events	0 / 248	not stated; safety; registry:adverse_events
A3	events	0 / 248	not stated; safety; pancreatitis; registry:adverse_events
A3	events	0 / 248	not stated; safety; oedematous pancreatitis; registry:adverse_events
A3	events	0 / 28	not stated; other; registry:adverse_events
A3	events	0 / 28	not stated; other; oedematous pancreatitis; registry:adverse_events
A3	events	0 / 28	not stated; other; pancreatitis; registry:adverse_events

Thyroid cancer (any) (6 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 251	not stated; safety; registry:adverse_events
A1	events	0 / 53	not stated; other; registry:adverse_events
A2	events	0 / 62	not stated; other; registry:adverse_events
A2	events	1 / 246	not stated; safety; registry:adverse_events
A3	events	0 / 248	not stated; safety; registry:adverse_events
A3	events	0 / 28	not stated; other; registry:adverse_events

Suicidal ideation or behavior (6 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 53	not stated; other; suicidal ideation; registry:adverse_events
A1	events	1 / 251	not stated; safety; suicidal ideation; registry:adverse_events
A2	events	0 / 246	not stated; safety; suicidal ideation; registry:adverse_events
A2	events	0 / 62	not stated; other; suicidal ideation; registry:adverse_events
A3	events	0 / 248	not stated; safety; suicidal ideation; registry:adverse_events
A3	events	0 / 28	not stated; other; suicidal ideation; registry:adverse_events

Intestinal obstruction or ileus (12 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 251	not stated; safety; ileus; registry:adverse_events
A1	events	0 / 251	not stated; safety; intestinal obstruction; registry:adverse_events
A1	events	0 / 53	not stated; other; ileus; registry:adverse_events
A1	events	0 / 53	not stated; other; intestinal obstruction; registry:adverse_events
A2	events	0 / 246	not stated; safety; ileus; registry:adverse_events
A2	events	0 / 62	not stated; other; ileus; registry:adverse_events
A2	events	0 / 246	not stated; safety; intestinal obstruction; registry:adverse_events
A2	events	0 / 62	not stated; other; intestinal obstruction; registry:adverse_events
A3	events	0 / 28	not stated; other; ileus; registry:adverse_events
A3	events	1 / 248	not stated; safety; ileus; registry:adverse_events
A3	events	1 / 248	not stated; safety; intestinal obstruction; registry:adverse_events
A3	events	0 / 28	not stated; other; intestinal obstruction; registry:adverse_events