parallel randomized trial

NCT00960661

A Randomized Trial Comparing Two Therapies: Basal Insulin/Glargine, Exenatide and Metformin Therapy (BET) or Basal Insulin/Glargine, Bolus Insulin Lispro and Metformin Therapy (BBT) in Subjects With Type 2 Diabetes Who Were Previously Treated by Basal Insulin Glargine With Either Metformin or Metformin and Sulfonylurea

Type 2 diabetes (adults)NCT00960661S000609

Design

Randomized: 637
Start year: 2009
Treatment: 30 weeks, follow-up 30 weeks
Countries: Argentina, Belgium, Estonia, Finland, France, Germany, Greece, Italy, South Korea, Mexico, Netherlands, Portugal, Romania, Russian Federation, Spain, Sweden, United Kingdom (108 sites)
Sponsor: AstraZeneca (industry)
Eligibility: age 18 or older; T2D on insulin glargine and metformin with or without sulfonylurea; HbA1c 7.0 to 10.0; BMI 25.0 (23.0 in South Korea) to 45.0; HbA1c above 7.0 after optimization

Conduct and analysis

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

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Exenatide 10 ug subcutaneous twice daily Exenatide twice daily plus insulin glargine	insulin glargine titrated (cut 10 percent or more if HbA1c 8.0 or less) plus metformin; lifestyle: not reported	316	247
A2	Insulin lispro (prandial) Insulin lispro thrice daily plus insulin glargine	insulin glargine titrated plus metformin; lifestyle: not reported	321	263

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	Insulin lispro (prandial) A2
age: 65 or older	n	67	81
age	mean (years)	59.5	59.4
age	sd (years)	9.6	9.3
asian	n	11	14
asian	percent	5	5
black	n	2	1
bmi	mean (kg/m2)	32.7	32.3
bmi	sd (kg/m2)	4.7	4.7
diabetes duration	median (years)	12	11
diabetes duration	q1 (years)	8	8
diabetes duration	q3 (years)	17	15
female	n	119	130
hba1c	mean (percent)	8.3	8.2
hba1c	sd (percent)	1.0	0.9
insulin dose	mean (U/day)	61.5	61.1
insulin dose	median (U/day)	54	52
insulin dose	q1 (U/day)	40	38
insulin dose	q3 (U/day)	76	76
insulin dose	sd (U/day)	30.9	35.2
other race american indian alaska native	n	12	18
other race american indian alaska native	percent	5	7
sbp	mean (mmHg)	137	135
sbp	sd (mmHg)	16	15
waist	mean (cm)	108	108
waist	sd (cm)	13	13
weight	mean (kg)	89.9	89.3
weight	sd (kg)	16.7	17.3
white	n	222	229
white	percent	90	87

Analyses this trial contributes to

Results

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

HbA1c change (14 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	-10.7 mmol/mol	1.0		107	not stated; modified itt; bmi:less_than_30; R0025286:Table 2
30	A1	change	-1.10 percent		-1.20 to -1.00		not stated; modified itt; R0016788:Results
30	A1	change	-11.9 mmol/mol	1.2		88	not stated; modified itt; bmi:more_than_35; R0025286:Table 2
30	A1 vs A2	md	-0.04 percent		-0.18 to 0.11		not stated; per protocol; R0016788:Table 2
30	A1	change	-1.5 percent	1.2		10	not stated; per protocol; region:korea; R0014077:Results
30	A1 vs A2	md	-0.03 percent		-0.16 to 0.11		not stated; modified itt; R0016788:Results
30	A1	change	-10.9 mmol/mol	0.8		120	not stated; modified itt; bmi:30_to_35; R0025286:Table 2
30	A1	change	-1.13 percent	0.05		247	not stated; per protocol; R0016788:Table 2
30	A2	change	-1.0 percent	1.0		13	not stated; per protocol; region:korea; R0014077:Results
30	A2	change	-1.07 percent		-1.17 to -0.97		not stated; modified itt; R0016788:Results
30	A2	change	-1.10 percent	0.05		263	not stated; per protocol; R0016788:Table 2
30	A2	change	-11.0 mmol/mol	0.9		111	not stated; modified itt; bmi:30_to_35; R0025286:Table 2
30	A2	change	-9.6 mmol/mol	0.9		113	not stated; modified itt; bmi:less_than_30; R0025286:Table 2
30	A2	change	-12.4 mmol/mol	1.0		88	not stated; modified itt; bmi:more_than_35; R0025286:Table 2

Body weight change in kilograms (diabetes) (14 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A2	md	-4.5 kg		-5.2 to -3.9		not stated; modified itt; R0016788:Supplement Table 3
30	A1	change	-2.5 kg	0.3		247	not stated; per protocol; R0016788:Table 2
30	A1	change	-2.6 kg	0.2			not stated; modified itt; R0016788:Supplement Table 3
30	A1 vs A2	md	-4.6 kg		-5.2 to -3.9		not stated; per protocol; R0016788:Table 2
30	A1	change	-2.0 kg	0.3		120	not stated; modified itt; bmi:30_to_35; R0025286:Table 2
30	A1	change	-2.1 kg	0.3		107	not stated; modified itt; bmi:less_than_30; R0025286:Table 2
30	A1	change	-3.6 kg	0.6		88	not stated; modified itt; bmi:more_than_35; R0025286:Table 2
30	A1	change	-0.7 kg	3.3		10	not stated; per protocol; region:korea; R0014077:Results
30	A2	change	2.1 kg	0.2		263	not stated; per protocol; R0016788:Table 2
30	A2	change	1.8 kg	0.3		113	not stated; modified itt; bmi:less_than_30; R0025286:Table 2
30	A2	change	1.5 kg	0.3		111	not stated; modified itt; bmi:30_to_35; R0025286:Table 2
30	A2	change	2.3 kg	0.5		88	not stated; modified itt; bmi:more_than_35; R0025286:Table 2
30	A2	change	1.9 kg	0.2			not stated; modified itt; R0016788:Supplement Table 3
30	A2	change	1.0 kg	2.7		13	not stated; per protocol; region:korea; R0014077:Results

HbA1c below 7 percent (4 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
30	A1	responders	49.6	42.6 to 55.4	247	not stated; per protocol; R0016788:Table 2
30	A1	responders	46.7		244	not stated; per protocol; registry:outcomes
30	A2	responders	42.6		263	not stated; per protocol; registry:outcomes
30	A2	responders	49.0	42.9 to 55.3	263	not stated; per protocol; R0016788:Table 2

Level 2 or 3 hypoglycemia (participants) (4 lines; O04)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		2 / 315	not stated; other; R0016788:Results
A1	events	30	315	not stated; other; R0016788:Results
A2	events	41	312	not stated; other; R0016788:Results
A2	events		7 / 312	not stated; other; R0016788:Results

Level 2 or 3 hypoglycemia (episode rate) (6 lines; O04B)

Arm	Statistic	Estimate	Detail
A1	rate		not stated; other; R0016788:Supplement Table 4
A1	rate		not stated; other; R0016788:Supplement Table 4
A1	rate	0.0	not stated; safety; registry:outcomes
A2	rate		not stated; other; R0016788:Supplement Table 4
A2	rate		not stated; other; R0016788:Supplement Table 4
A2	rate	0.1	not stated; safety; registry:outcomes

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A2	md	-4.5 mmHg		-7.0 to -2.0		not stated; per protocol; R0016788:Table 2
30	A1	change	-4.1 mmHg	1.0		207	not stated; per protocol; R0016788:Table 2
30	A2	change	0.4 mmHg	0.9		227	not stated; per protocol; R0016788:Table 2

Acute kidney injury (3 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	1 / 315	not stated; other; R0016788:Results
A1	events	1 / 315	not stated; safety; registry:adverse_events
A2	events	0 / 312	not stated; safety; registry:adverse_events

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 315	not stated; other; R0016788:Figure 1
	A2	events				0 / 312	not stated; other; R0016788:Figure 1

Hospitalization for heart failure (4 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 315	not stated; safety; cardiac failure; registry:adverse_events
A1	events	1 / 315	not stated; safety; cardiac failure congestive; registry:adverse_events
A2	events	0 / 312	not stated; safety; cardiac failure congestive; registry:adverse_events
A2	events	1 / 312	not stated; safety; cardiac failure; registry:adverse_events

Physical functioning (any instrument) (3 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	Detail
30	A1	change	5.48 points	0.96	not stated; modified itt; R0016788:Supplement Table 5
30	A1 vs A2	md	4.84 points	1.41	not stated; modified itt; R0016788:Supplement Table 5
30	A2	change	1.66 points	0.95	not stated; modified itt; R0016788:Supplement Table 5

Health related quality of life total score (any instrument) (6 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	Detail
30	A1	change	2.19 points	0.18	not stated; modified itt; R0016788:Supplement Table 5
30	A1	change	4.40 points	0.80	not stated; modified itt; R0016788:Supplement Table 5
30	A1 vs A2	md	0.80 points	0.23	not stated; modified itt; R0016788:Supplement Table 5
30	A1 vs A2	md	3.88 points	1.02	not stated; modified itt; R0016788:Supplement Table 5
30	A2	change	1.40 points	0.18	not stated; modified itt; R0016788:Supplement Table 5
30	A2	change	0.51 points	0.80	not stated; modified itt; R0016788:Supplement Table 5

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	18 / 315	not stated; other; R0016788:Supplement Table 4
A1	events	23 / 315	not stated; safety; registry:adverse_events
A2	events	23 / 312	not stated; other; R0016788:Supplement Table 4
A2	events	26 / 312	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (34 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 315	not stated; other; cholecystitis chronic; R0016788:Supplement Table 4
A1	events	17 / 315	not stated; other; R0016788:Supplement Table 4
A1	events	0 / 315	not stated; other; acute myocardial infarction; R0016788:Supplement Table 4
A1	events	0 / 315	not stated; other; coronary artery bypass; R0016788:Supplement Table 4
A1	events	1 / 315	not stated; other; decreased appetite; R0016788:Supplement Table 4
A1	events	1 / 315	not stated; other; dermatitis allergic; R0016788:Supplement Table 4
A1	events	1 / 315	not stated; other; diarrhea; R0016788:Supplement Table 4
A1	events	1 / 315	not stated; other; dizziness; R0016788:Supplement Table 4
A1	events	0 / 315	not stated; other; dry mouth; R0016788:Supplement Table 4
A1	events	0 / 315	not stated; other; fear of weight gain; R0016788:Supplement Table 4
A1	events	0 / 315	not stated; other; gout; R0016788:Supplement Table 4
A1	events	1 / 315	not stated; other; lower limb fracture; R0016788:Supplement Table 4
A1	events	9 / 315	not stated; other; nausea; R0016788:Supplement Table 4
A1	events	1 / 315	not stated; other; pancreatic carcinoma; R0016788:Supplement Table 4
A1	events	0 / 315	not stated; other; rash generalized; R0016788:Supplement Table 4
A1	events	0 / 315	not stated; other; urinary tract infection; R0016788:Supplement Table 4
A1	events	2 / 315	not stated; other; vomiting; R0016788:Supplement Table 4
A2	events	8 / 312	not stated; other; R0016788:Supplement Table 4
A2	events	1 / 312	not stated; other; acute myocardial infarction; R0016788:Supplement Table 4
A2	events	1 / 312	not stated; other; cholecystitis chronic; R0016788:Supplement Table 4
A2	events	1 / 312	not stated; other; coronary artery bypass; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; decreased appetite; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; dermatitis allergic; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; diarrhea; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; dizziness; R0016788:Supplement Table 4
A2	events	1 / 312	not stated; other; dry mouth; R0016788:Supplement Table 4
A2	events	1 / 312	not stated; other; fear of weight gain; R0016788:Supplement Table 4
A2	events	1 / 312	not stated; other; gout; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; lower limb fracture; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; nausea; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; pancreatic carcinoma; R0016788:Supplement Table 4
A2	events	1 / 312	not stated; other; rash generalized; R0016788:Supplement Table 4
A2	events	1 / 312	not stated; other; urinary tract infection; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; vomiting; R0016788:Supplement Table 4

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	102 / 315	not stated; other; R0016788:Supplement Table 4
A1	events	1 / 315	not stated; safety; registry:adverse_events
A2	events	5 / 312	not stated; other; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; safety; registry:adverse_events

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				39 / 315	not stated; other; R0016788:Supplement Table 4
	A2	events				3 / 312	not stated; other; R0016788:Supplement Table 4

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				34 / 315	not stated; other; R0016788:Supplement Table 4
	A2	events				16 / 312	not stated; other; R0016788:Supplement Table 4

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	7 / 315	not stated; safety; registry:adverse_events
A1	events	0 / 315	not stated; safety; registry:adverse_events
A2	events	2 / 312	not stated; safety; registry:adverse_events
A2	events	1 / 312	not stated; safety; registry:adverse_events

Discontinuation due to gastrointestinal adverse events (8 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	1 / 315	not stated; other; diarrhea; R0016788:Supplement Table 4
A1	events	0 / 315	not stated; other; dry mouth; R0016788:Supplement Table 4
A1	events	9 / 315	not stated; other; nausea; R0016788:Supplement Table 4
A1	events	2 / 315	not stated; other; vomiting; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; diarrhea; R0016788:Supplement Table 4
A2	events	1 / 312	not stated; other; dry mouth; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; nausea; R0016788:Supplement Table 4
A2	events	0 / 312	not stated; other; vomiting; R0016788:Supplement Table 4

Gallbladder and biliary disease (4 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 315	not stated; safety; cholecystitis acute; registry:adverse_events
A1	events	0 / 315	not stated; safety; cholecystitis chronic; registry:adverse_events
A2	events	1 / 312	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	1 / 312	not stated; safety; cholecystitis chronic; registry:adverse_events

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 315	not stated; other; pancreatitis; R0016788:Results
	A2	events				0 / 312	not stated; other; pancreatitis; R0016788:Results

Medullary thyroid carcinoma (1 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 315	not stated; other; R0016788:Results

Thyroid cancer (any) (1 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 315	not stated; other; R0016788:Results

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	1 / 315	not stated; safety; diabetic retinopathy; registry:adverse_events
A1	events	2 / 315	not stated; safety; vitreous haemorrhage; registry:adverse_events
A2	events	0 / 312	not stated; safety; diabetic retinopathy; registry:adverse_events
A2	events	0 / 312	not stated; safety; vitreous haemorrhage; registry:adverse_events

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 315	not stated; other; R0016788:Results
	A2	events				0 / 312	not stated; other; R0016788:Figure 1

Pancreatic cancer (3 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	1 / 315	not stated; other; R0016788:Results
A1	events	1 / 315	not stated; safety; registry:adverse_events
A2	events	0 / 312	not stated; safety; registry:adverse_events

Any cancer (1 lines; O39)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 315	not stated; other; R0016788:Results