parallel randomized trial

NCT01029886

Safety and Efficacy of Exenatide Once Weekly Versus Liraglutide in Subjects With Type 2 Diabetes and Inadequate Glycemic Control Treated With Lifestyle Modification and Oral Antidiabetic Medications

Type 2 diabetes (adults)NCT01029886S000352

Design

Randomized: 912
Start year: 2010
Treatment: 26 weeks, follow-up 36 weeks
Countries: Argentina, Australia, Austria, Belgium, Canada, Czech Republic, France, Germany, Hungary, Israel, Italy, Mexico, Poland, Romania, Slovakia, South Africa, South Korea, Spain, Taiwan (105 sites)
Sponsor: Eli Lilly and Company and Amylin Pharmaceuticals LLC (industry)
Eligibility: adults 18 or older with type 2 diabetes on oral agents, HbA1c 7.1 to 11.0 percent, BMI 45 or less

Conduct and analysis

Blinding: open label
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: modified itt
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Exenatide extended release 2 mg subcutaneous once weekly Exenatide once weekly 2 mg	metformin, sulfonylurea or pioglitazone alone or in combination; lifestyle: not reported	461	461
A2	Liraglutide 1.8 mg subcutaneous once daily Liraglutide 1.8 mg once daily	metformin, sulfonylurea or pioglitazone alone or in combination; lifestyle: not reported	451	450

Baseline characteristics

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

Characteristic	Statistic	Exenatide extended release 2 mg subcutaneous once weekly A1	Liraglutide 1.8 mg subcutaneous once daily A2
age	mean (years)	57	57
age	sd (years)	9.4	9.6
asian	n	55	56
asian	percent	12	12
black	n	4	4
black	percent	1	1
bmi	mean (kg/m2)	32.3	32.3
bmi	sd (kg/m2)	5.6	5.4
diabetes duration	mean (years)	8	9
diabetes duration	sd (years)	6	6
female	n	207	205
female	percent	45	46
hba1c	mean (percent)	8.5	8.4
hba1c	sd (percent)	1.0	1.0
hispanic	n	98	99
hispanic	percent	21	22
metformin use	n	436	425
other background: metformin and pioglitazone	n	16	18
other background: metformin and pioglitazone	percent	4	4
other background: metformin and sulfonylurea and pioglitazone	n	1	1
other background: metformin and sulfonylurea	n	275	277
other background: metformin and sulfonylurea	percent	60	62
other background: metformin only	n	150	136
other background: metformin only	percent	33	30
other background: pioglitazone only	n	1	0
other background: pioglitazone only	percent		0
other background: sulfonylurea only	n	18	18
other background: sulfonylurea only	percent	4	4
other race american indian alaska native	n	16	16
other race american indian alaska native	percent	4	4
other race multiple	n	2	4
other race multiple	percent		1
other race native hawaiian pacific islander	n	0	1
other race native hawaiian pacific islander	percent	0
sbp	mean (mmHg)	132	134
sbp	sd (mmHg)	14	14
weight	mean (kg)	90.9	91.1
weight	sd (kg)	19.5	19.1
white	n	384	369
white	percent	83	82

Analyses this trial contributes to

Results

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

HbA1c change (10 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
22	A1 vs A2	md	percent		0.08 to 0.32		not stated; modified itt; R0016299:Figure 2
26	A1 vs A2	md	0.21 percent	0.07	0.08 to 0.33		not stated; modified itt; R0016299:Table 2
26	A1	change	-1.75 percent	0.09	-1.92 to -1.58	136	not stated; modified itt; hba1c:9_or_more; R0016299:Table 2
26	A1 vs A2	md	0.29 percent	0.12	0.06 to 0.53		not stated; modified itt; hba1c:9_or_more; R0016299:Table 2
26	A1	change	-1.05 percent	0.06	-1.16 to -0.94	314	not stated; modified itt; hba1c:less_than_9; R0016299:Table 2
26	A1 vs A2	md	0.15 percent	0.08	0.00 to 0.30		not stated; modified itt; hba1c:less_than_9; R0016299:Table 2
26	A1	change	-1.28 percent	0.05	-1.38 to -1.18	390	not stated; modified itt; R0016299:Table 2
26	A2	change	-1.20 percent	0.06	-1.31 to -1.09	308	not stated; modified itt; hba1c:less_than_9; R0016299:Table 2
26	A2	change	-2.04 percent	0.09	-2.21 to -1.87	136	not stated; modified itt; hba1c:9_or_more; R0016299:Table 2
26	A2	change	-1.48 percent	0.05	-1.58 to -1.38	386	not stated; modified itt; R0016299:Table 2

Body weight change in kilograms (diabetes) (10 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
22	A1 vs A2	md	kg		0.42 to 1.36		not stated; modified itt; R0016299:Figure 3
26	A1	change	-2.16 kg	0.32	-2.78 to -1.54	168	not stated; modified itt; bmi:less_than_30; R0016299:Table 2
26	A1 vs A2	md	1.10 kg	0.30	0.51 to 1.69		not stated; modified itt; bmi:30_or_more; R0016299:Table 2
26	A1	change	-2.52 kg	0.24	-2.99 to -2.05	290	not stated; modified itt; bmi:30_or_more; R0016299:Table 2
26	A1 vs A2	md	0.49 kg	0.40	-0.29 to 1.26		not stated; modified itt; bmi:less_than_30; R0016299:Table 2
26	A1	change	-2.68 kg	0.18	-3.03 to -2.32	404	not stated; modified itt; R0016299:Table 2
26	A1 vs A2	md	0.90 kg	0.26	0.39 to 1.40		not stated; modified itt; R0016299:Table 2
26	A2	change	-3.57 kg	0.18	-3.94 to -3.21	398	not stated; modified itt; R0016299:Table 2
26	A2	change	-3.62 kg	0.24	-4.09 to -3.15	286	not stated; modified itt; bmi:30_or_more; R0016299:Table 2
26	A2	change	-2.65 kg	0.32	-3.28 to -2.02	164	not stated; modified itt; bmi:less_than_30; R0016299:Table 2

HbA1c below 7 percent (2 lines; O03)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	responders				243 / 461	not stated; modified itt; R0016299:Results
26	A2	responders				271 / 450	not stated; modified itt; R0016299:Results

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 461	while on treatment; modified itt; R0016299:Results
	A2	events				0 / 450	while on treatment; modified itt; R0016299:Results

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-2.48 mmHg	0.56	-3.58 to -1.37	404	not stated; modified itt; R0016299:Table 2
26	A1 vs A2	md	0.97 mmHg	0.76	-0.53 to 2.47		not stated; modified itt; R0016299:Table 2
26	A2	change	-3.45 mmHg	0.57	-4.57 to -2.33	398	not stated; modified itt; R0016299:Table 2

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 461	not stated; modified itt; R0011287:Table 3
A1	events	2 / 461	not stated; modified itt; R0016299:Results
A2	events	2 / 450	not stated; modified itt; R0016299:Results
A2	events	1 / 450	not stated; modified itt; R0011287:Table 3

Three point MACE (1 lines; O21)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	events	0.9			450	not stated; modified itt; R0011287:Results

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				13 / 461	while on treatment; modified itt; R0016299:Table 3
	A2	events				7 / 450	while on treatment; modified itt; R0016299:Table 3

Discontinuation due to adverse events (42 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	12 / 461	while on treatment; modified itt; R0016299:Results
A1	events	2 / 461	while on treatment; modified itt; abdominal pain; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; acute cholecystitis; R0016299:Table 3
A1	events	0 / 461	while on treatment; modified itt; asthenia; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; prostate cancer; R0016299:Table 3
A1	events	0 / 461	while on treatment; modified itt; brain stem infarction; R0016299:Table 3
A1	events	0 / 461	while on treatment; modified itt; decreased appetite; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; diarrhoea; R0016299:Table 3
A1	events	0 / 461	while on treatment; modified itt; dyspepsia; R0016299:Table 3
A1	events	0 / 461	while on treatment; modified itt; fatigue; R0016299:Table 3
A1	events	0 / 461	while on treatment; modified itt; gastritis; R0016299:Table 3
A1	events	0 / 461	while on treatment; modified itt; gastroenteritis; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; injection-site nodule; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; myocardial infarction; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; nausea; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; pancreatitis; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; blood amylase increase; R0016299:Table 3
A1	events	12 / 461	not stated; modified itt; R0011287:Table 3
A1	events	12 / 461	not stated; modified itt; R0016299:Figure 1
A1	events	1 / 461	while on treatment; modified itt; subcutaneous nodule; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; vomiting; R0016299:Table 3
A2	events	1 / 450	while on treatment; modified itt; decreased appetite; R0016299:Table 3
A2	events	23 / 450	not stated; modified itt; R0011287:Table 3
A2	events	25 / 450	not stated; modified itt; R0016299:Figure 1
A2	events	24 / 450	while on treatment; modified itt; R0016299:Results
A2	events	0 / 450	while on treatment; modified itt; abdominal pain; R0016299:Table 3
A2	events	0 / 450	while on treatment; modified itt; acute cholecystitis; R0016299:Table 3
A2	events	1 / 450	while on treatment; modified itt; asthenia; R0016299:Table 3
A2	events	0 / 450	while on treatment; modified itt; blood amylase increase; R0016299:Table 3
A2	events	1 / 450	while on treatment; modified itt; brain stem infarction; R0016299:Table 3
A2	events	3 / 450	while on treatment; modified itt; diarrhoea; R0016299:Table 3
A2	events	2 / 450	while on treatment; modified itt; dyspepsia; R0016299:Table 3
A2	events	1 / 450	while on treatment; modified itt; fatigue; R0016299:Table 3
A2	events	1 / 450	while on treatment; modified itt; gastritis; R0016299:Table 3
A2	events	1 / 450	while on treatment; modified itt; gastroenteritis; R0016299:Table 3
A2	events	0 / 450	while on treatment; modified itt; injection-site nodule; R0016299:Table 3
A2	events	0 / 450	while on treatment; modified itt; myocardial infarction; R0016299:Table 3
A2	events	9 / 450	while on treatment; modified itt; nausea; R0016299:Table 3
A2	events	0 / 450	while on treatment; modified itt; pancreatitis; R0016299:Table 3
A2	events	0 / 450	while on treatment; modified itt; prostate cancer; R0016299:Table 3
A2	events	0 / 450	while on treatment; modified itt; subcutaneous nodule; R0016299:Table 3
A2	events	4 / 450	while on treatment; modified itt; vomiting; R0016299:Table 3

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	43 / 461	while on treatment; modified itt; R0016299:Table 3
A1	events	50 / 461	not stated; modified itt; R0009388:Supplement Table S4
A2	events	93 / 450	while on treatment; modified itt; R0016299:Table 3
A2	events	103 / 450	not stated; modified itt; R0009388:Supplement Table S4

Vomiting (3 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	17 / 461	while on treatment; modified itt; R0016299:Table 3
A2	events	48 / 450	while on treatment; modified itt; R0016299:Table 3
A2	events	47 / 450	not stated; safety; registry:adverse_events

Diarrhea (5 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	28 / 461	while on treatment; modified itt; R0016299:Table 3
A1	events	31 / 461	not stated; modified itt; R0009388:Supplement Table S4
A2	events	59 / 450	while on treatment; modified itt; R0016299:Table 3
A2	events	64 / 450	not stated; modified itt; R0009388:Supplement Table S4
A2	events	58 / 450	not stated; safety; registry:adverse_events

Constipation (3 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	22 / 461	not stated; modified itt; R0009388:Supplement Table S4
A1	events	21 / 461	while on treatment; modified itt; R0016299:Table 3
A2	events	22 / 450	while on treatment; modified itt; R0016299:Table 3

Discontinuation due to gastrointestinal adverse events (16 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	6 / 461	not stated; modified itt; R0011287:Table 3
A1	events	0 / 461	while on treatment; modified itt; R0016299:Results
A1	events	2 / 461	while on treatment; modified itt; abdominal pain; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; diarrhoea; R0016299:Table 3
A1	events	0 / 461	while on treatment; modified itt; dyspepsia; R0016299:Table 3
A1	events	0 / 461	while on treatment; modified itt; gastritis; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; nausea; R0016299:Table 3
A1	events	1 / 461	while on treatment; modified itt; vomiting; R0016299:Table 3
A2	events	2 / 450	while on treatment; modified itt; dyspepsia; R0016299:Table 3
A2	events	18 / 450	not stated; modified itt; R0011287:Table 3
A2	events	0 / 450	while on treatment; modified itt; abdominal pain; R0016299:Table 3
A2	events	3 / 450	while on treatment; modified itt; diarrhoea; R0016299:Table 3
A2	events	1 / 450	while on treatment; modified itt; gastritis; R0016299:Table 3
A2	events	9 / 450	while on treatment; modified itt; nausea; R0016299:Table 3
A2	events	4 / 450	while on treatment; modified itt; vomiting; R0016299:Table 3
A2	events	15 / 450	while on treatment; modified itt; R0016299:Results

Gallbladder and biliary disease (4 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 461	while on treatment; modified itt; cholelithiasis; R0016299:Results
A1	events	1 / 461	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	0 / 450	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	0 / 450	not stated; safety; cholecystitis acute; registry:adverse_events

Acute pancreatitis (5 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 461	while on treatment; modified itt; R0016299:Results
A1	events	1 / 461	while on treatment; modified itt; pancreatitis; R0016299:Results
A2	events	0 / 450	not stated; safety; registry:adverse_events
A2	events	0 / 450	not stated; modified itt; R0009388:Supplement Table S4
A2	events	0 / 450	not stated; modified itt; pancreatitis; R0009388:Supplement Table S4

Medullary thyroid carcinoma (2 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 461	not stated; modified itt; R0011287:Results
	A2	events				0 / 450	not stated; modified itt; R0011287:Results

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 461	not stated; modified itt; R0011287:Results
	A2	events				0 / 450	not stated; modified itt; R0011287:Results

Death by suicide (1 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 461	not stated; modified itt; R0011287:Table 3

Gastroparesis (2 lines; O37A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 461	not stated; modified itt; impaired gastric emptying; R0009388:Supplement Table S4
	A2	events				0 / 450	not stated; modified itt; impaired gastric emptying; R0009388:Supplement Table S4

Intestinal obstruction or ileus (2 lines; O37B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 461	not stated; modified itt; R0009388:Supplement Table S4
	A2	events				0 / 450	not stated; modified itt; R0009388:Supplement Table S4

Pancreatic cancer (2 lines; O38)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 461	not stated; modified itt; R0011287:Results
	A2	events				0 / 450	not stated; modified itt; R0011287:Results