parallel randomized trial

NCT00765817

A Randomized Trial Comparing Exenatide With Placebo in Subjects With Type 2 Diabetes on Insulin Glargine With or Without Oral Antihyperglycemic Medications

Type 2 diabetes (adults)NCT00765817S000345

Design

Randomized: 261
Start year: 2008
Treatment: 30 weeks, follow-up 30 weeks
Countries: Greece, Israel, Mexico, United Kingdom, United States (55 sites)
Sponsor: Alliance of Eli Lilly and Company and Amylin Pharmaceuticals (industry)
Eligibility: adults 18 or older; insulin glargine 20 U/d or more alone or with metformin or pioglitazone; HbA1c 7.1 to 10.5 percent; BMI 45 or less

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: full analysis
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Exenatide 10 ug subcutaneous twice daily Exenatide twice daily plus glargine	insulin glargine titrated to fasting glucose below 5.6 mmol/L, with or without metformin or pioglitazone; lifestyle: not reported	138	137
A2	Placebo Placebo plus glargine	insulin glargine titrated to fasting glucose below 5.6 mmol/L, with or without metformin or pioglitazone; lifestyle: not reported	123	122

Baseline characteristics

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

Characteristic	Statistic	Exenatide 10 ug subcutaneous twice daily A1	Placebo A2
age: 65 or older	n	37	38
age	mean (years)	59	59
age	sd (years)	9	10
asian	n	5	2
asian	percent	4	2
black	n	14	9
black	percent	10	7
bmi	mean (kg/m2)	33.8	33.1
bmi	sd (kg/m2)	5.8	6.2
diabetes duration: 10 or more	n	87	75
diabetes duration: 10 or more	percent	64	62
diabetes duration: 20 or more	n	20	15
diabetes duration: 20 or more	percent	15	12
diabetes duration	mean (years)	12	12
diabetes duration	sd (years)	7	7
female	n	67	44
female	percent	49	36
hba1c: 8.0 or less	n	60	43
hba1c: 8.0 or less	percent	44	35
hba1c: more than 8.0	n	77	79
hba1c: more than 8.0	percent	56	65
hba1c	mean (percent)	8.32	8.50
hba1c	sd (percent)	0.85	0.96
hispanic	n	44	43
hispanic	percent	32	35
insulin dose	mean (U/kg/day)	0.51	0.50
insulin dose	sd (U/kg/day)	0.28	0.24
other background: metformin and pioglitazone	n	23	8
other background: metformin and pioglitazone	percent	17	7
other background: metformin only	n	91	91
other background: metformin only	percent	66	75
other background: none	n	21	17
other background: none	percent	15	14
other background: pioglitazone only	n	2	6
other background: pioglitazone only	percent	2	5
other race american indian alaska native	n	13	13
other race american indian alaska native	percent	10	11
other race multiple	n	2	0
other race multiple	percent	2	0
sbp	mean (mmHg)	130.0	128.1
sbp	sd (mmHg)	15.9	13.4
waist	mean (cm)	110	110
waist	sd (cm)	14	16
weight	mean (kg)	95.4	93.4
weight	sd (kg)	20.4	21.2
white	n	103	98
white	percent	75	80

Analyses this trial contributes to

Results

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

HbA1c change (23 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A2	md	-0.75 percent				not stated; modified itt; hba1c:more_than_8; R0026563:Results
30	A1	change	-1.59 percent		-1.75 to -1.42		not stated; full analysis; R0027069:Appendix Table 3
30	A1	change	-1.71 percent	0.09		112	not stated; full analysis; registry:outcomes
30	A1 vs A2	md	-0.69 percent		-0.93 to -0.46		not stated; full analysis; R0027069:Table 2
30	A1 vs A2	md	percent				not stated; full analysis; registry:outcomes
30	A1 vs A2	md	-0.53 percent		-0.76 to -0.31		not stated; full analysis; R0027069:Appendix Table 3
30	A1 vs A2	md	-0.39 percent				not stated; modified itt; bmi:more_than_36; R0026563:Results
30	A1 vs A2	md	-0.78 percent				not stated; modified itt; diabetes_duration:9_to_15; R0026563:Results
30	A1 vs A2	md	-0.31 percent				not stated; modified itt; diabetes_duration:less_than_9; R0026563:Results
30	A1 vs A2	md	-0.82 percent				not stated; modified itt; diabetes_duration:more_than_15; R0026563:Results
30	A1 vs A2	md	-0.52 percent				not stated; modified itt; hba1c:8_or_less; R0026563:Results
30	A1	change	-1.74 percent		-1.91 to -1.56	137	not stated; full analysis; R0027069:Table 2
30	A1	change	-16.5 mmol/mol	1.6		50	not stated; modified itt; bmi:30_to_35; R0025286:Table 2
30	A1 vs A2	md	-0.85 percent				not stated; modified itt; bmi:30_to_36; R0026563:Results
30	A1	change	-12.5 mmol/mol	2.0		36	not stated; modified itt; bmi:less_than_30; R0025286:Table 2
30	A1 vs A2	md	-0.62 percent				not stated; modified itt; bmi:less_than_30; R0026563:Results
30	A1	change	-16.5 mmol/mol	1.4		51	not stated; modified itt; bmi:more_than_35; R0025286:Table 2
30	A2	change	-1.04 percent		-1.22 to -0.86	122	not stated; full analysis; R0027069:Table 2
30	A2	change	-1.00 percent	0.09		100	not stated; full analysis; registry:outcomes
30	A2	change	-1.05 percent		-1.24 to -0.87		not stated; full analysis; R0027069:Appendix Table 3
30	A2	change	-9.6 mmol/mol	1.6		43	not stated; modified itt; bmi:less_than_30; R0025286:Table 2
30	A2	change	-9.8 mmol/mol	2.1		35	not stated; modified itt; bmi:30_to_35; R0025286:Table 2
30	A2	change	-11.9 mmol/mol	1.5		44	not stated; modified itt; bmi:more_than_35; R0025286:Table 2

Body weight change in kilograms (diabetes) (17 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A2	md	-1.9 kg				not stated; modified itt; diabetes_duration:9_to_15; R0026563:Results
30	A1	change	-1.78 kg		-2.48 to -1.08	137	not stated; full analysis; R0027069:Table 2
30	A1 vs A2	md	-2.74 kg		-3.74 to -1.74		not stated; full analysis; R0027069:Table 2
30	A1	change	-2.6 kg	0.6		50	not stated; modified itt; bmi:30_to_35; R0025286:Table 2
30	A1 vs A2	md	-2.9 kg				not stated; modified itt; bmi:30_to_36; R0026563:Results
30	A1	change	-0.4 kg	0.4		36	not stated; modified itt; bmi:less_than_30; R0025286:Table 2
30	A1 vs A2	md	-1.5 kg				not stated; modified itt; bmi:less_than_30; R0026563:Results
30	A1	change	-1.5 kg	0.6		51	not stated; modified itt; bmi:more_than_35; R0025286:Table 2
30	A1 vs A2	md	-3.0 kg				not stated; modified itt; bmi:more_than_36; R0026563:Results
30	A1 vs A2	md	-2.1 kg				not stated; modified itt; diabetes_duration:less_than_9; R0026563:Results
30	A1 vs A2	md	-3.9 kg				not stated; modified itt; diabetes_duration:more_than_15; R0026563:Results
30	A1 vs A2	md	-1.9 kg				not stated; modified itt; hba1c:8_or_less; R0026563:Results
30	A1 vs A2	md	-3.0 kg				not stated; modified itt; hba1c:more_than_8; R0026563:Results
30	A2	change	1.2 kg	0.4		43	not stated; modified itt; bmi:less_than_30; R0025286:Table 2
30	A2	change	0.96 kg		0.23 to 1.70	122	not stated; full analysis; R0027069:Table 2
30	A2	change	1.2 kg	0.6		44	not stated; modified itt; bmi:more_than_35; R0025286:Table 2
30	A2	change	-0 kg	0.6		35	not stated; modified itt; bmi:30_to_35; R0025286:Table 2

HbA1c below 7 percent (5 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
30	A1	responders	58.3		127	not stated; full analysis; registry:outcomes
30	A1	responders	60	51 to 69	137	not stated; full analysis; R0027069:Table 2
30	A1 vs A2	rd	25	12 to 39		not stated; full analysis; R0027069:Table 2
30	A2	responders	35	25 to 45	122	not stated; full analysis; R0027069:Table 2
30	A2	responders	31.1		106	not stated; full analysis; registry:outcomes

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 137	not stated; full analysis; R0027069:Table 3
A1	events	34 / 137	not stated; full analysis; R0027069:Table 3
A1	events	23 / 137	not stated; full analysis; R0027069:Table 3
A2	events	35 / 122	not stated; full analysis; R0027069:Table 3
A2	events	32 / 122	not stated; full analysis; R0027069:Table 3
A2	events	1 / 122	not stated; full analysis; R0027069:Table 3

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

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	rate	1.4		137	not stated; full analysis; R0027069:Results
A1 vs A2	rate ratio	1.2	0.6 to 2.2		not stated; full analysis; R0027069:Results
A2	rate	1.2		122	not stated; full analysis; R0027069:Results

Systolic blood pressure change (4 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
30	A1	change	-2.7 mmHg	-5.2 to -0.3	137	not stated; full analysis; R0027069:Table 2
30	A1 vs A2	md	-4.4 mmHg	-7.8 to -1.0		not stated; full analysis; R0027069:Table 2
30	A1 vs A2	md	mmHg			not stated; full analysis; registry:outcomes
30	A2	change	1.7 mmHg	-0.9 to 4.3	122	not stated; full analysis; R0027069:Table 2

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 137	not stated; full analysis; R0027069:Results
	A2	events				0 / 122	not stated; full analysis; R0027069:Results

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 137	not stated; full analysis; R0027069:Table 3
	A2	events				1 / 122	not stated; full analysis; R0027069:Table 3

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				8 / 137	not stated; full analysis; R0027069:Table 3
	A2	events				11 / 122	not stated; full analysis; R0027069:Table 3

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				13 / 137	not stated; full analysis; R0027069:Table 3
	A2	events				1 / 122	not stated; full analysis; R0027069:Table 3

Nausea (3 lines; O27A)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			56 / 137	not stated; full analysis; R0027069:Table 3
A1 vs A2	rd	32	23 to 42		not stated; full analysis; R0027069:Results
A2	events			10 / 122	not stated; full analysis; R0027069:Table 3

Vomiting (3 lines; O27B)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			25 / 137	not stated; full analysis; R0027069:Table 3
A1 vs A2	rd	14	7 to 21		not stated; full analysis; R0027069:Results
A2	events			5 / 122	not stated; full analysis; R0027069:Table 3

Diarrhea (3 lines; O27C)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			25 / 137	not stated; full analysis; R0027069:Table 3
A1 vs A2	rd	10	2 to 18		not stated; full analysis; R0027069:Results
A2	events			10 / 122	not stated; full analysis; R0027069:Table 3

Constipation (3 lines; O27D)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			14 / 137	not stated; full analysis; R0027069:Table 3
A1 vs A2	rd	8	3 to 14		not stated; full analysis; R0027069:Results
A2	events			2 / 122	not stated; full analysis; R0027069:Table 3

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 137	not stated; full analysis; pancreatitis; R0027069:Results
	A2	events				0 / 122	not stated; full analysis; pancreatitis; R0027069:Results

Medullary thyroid carcinoma (2 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 137	not stated; full analysis; R0027069:Results
	A2	events				0 / 122	not stated; full analysis; R0027069:Results

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 137	not stated; full analysis; R0027069:Results
	A2	events				0 / 122	not stated; full analysis; R0027069:Results

Suicidal ideation or behavior (2 lines; O35A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 137	not stated; safety; suicide attempt; registry:adverse_events
	A2	events				1 / 122	not stated; safety; suicide attempt; registry:adverse_events

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 137	not stated; full analysis; R0027069:Table 3
	A2	events				0 / 122	not stated; full analysis; R0027069:Results

Intestinal obstruction or ileus (2 lines; O37B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 137	not stated; safety; small intestine obstruction; registry:adverse_events
	A2	events				1 / 122	not stated; safety; small intestine obstruction; registry:adverse_events

Pancreatic cancer (2 lines; O38)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 137	not stated; full analysis; R0027069:Results
	A2	events				0 / 122	not stated; full analysis; R0027069:Results

Any cancer (2 lines; O39)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 137	not stated; full analysis; R0027069:Results
	A2	events				0 / 122	not stated; full analysis; R0027069:Results