parallel randomized trial

NCT00637273

A Randomized, Double-Blind, Parallel-Group, Multicenter Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Long-Acting Release(Once Weekly) to Those of Sitagliptin and a Thiazolidinedione in Subjects With Type 2 Diabetes Mellitus Treated With Metformin

Type 2 diabetes (adults)NCT00637273S000402

Design

Randomized: 514
Start year: 2008
Treatment: 26 weeks, follow-up 26 weeks
Countries: United States, India, Mexico (72 sites)
Sponsor: Amylin Pharmaceuticals (registry lists AstraZeneca) (industry)
Eligibility: age 18 or older; HbA1c 7.1 to 11.0 percent; BMI 25 to 45; stable metformin

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	Exenatide extended release 2 mg subcutaneous once weekly Exenatide once weekly 2 mg	metformin; oral placebo capsule; lifestyle: not reported	170	160
A2	Sitagliptin Sitagliptin 100 mg daily	metformin; placebo injection weekly; lifestyle: not reported	172	166
A3	Pioglitazone Pioglitazone 45 mg daily	metformin; placebo injection weekly; lifestyle: not reported	172	165

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	Sitagliptin A2	Pioglitazone A3
age	mean (years)	52.4	52.2	53.0
age	sd (years)	10.41	10.54	9.92
asian	n	37	42	40
asian	percent	23	25	24
black	n	19	20	13
black	percent	12	12	8
bmi	mean (kg/m2)	32	32	33
bmi	sd (kg/m2)	5	5	5.5
diabetes duration	mean (years)	6	5	6
diabetes duration	sd (years)	5	4	5
egfr: 30 to 60	n	10	8	10
egfr: 60 to 90	n	85	85	98
female	n	71	80	86
female	percent	44	48	52
hba1c	mean (percent)	8.6	8.5	8.5
hba1c	sd (percent)	1.20	1.17	1.08
hispanic	n	50	49	44
hispanic	percent	31	30	27
other race other	n	1	5	3
other race other	percent	1	3	2
weight	mean (kg)	89.1	87.0	87.9
weight	sd (kg)	19.55	20.25	20.49
white	n	53	50	65
white	percent	33	30	39

Analyses this trial contributes to

Results

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

HbA1c change (5 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.55 percent	0.100		159	not stated; modified itt; registry:outcomes
26	A2	change	-0.92 percent	0.099		162	not stated; modified itt; registry:outcomes
26	A2 vs A1	md	0.63 percent		0.37 to 0.89		not stated; modified itt; registry:outcomes
26	A3	change	-1.23 percent	0.099		160	not stated; modified itt; registry:outcomes
26	A3 vs A1	md	0.32 percent		0.06 to 0.57		not stated; modified itt; registry:outcomes

Body weight change in kilograms (diabetes) (5 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-2.31 kg	0.323		160	not stated; modified itt; registry:outcomes
26	A2	change	-0.77 kg	0.322		163	not stated; modified itt; registry:outcomes
26	A2 vs A1	md	1.54 kg		0.72 to 2.35		not stated; modified itt; registry:outcomes
26	A3	change	2.79 kg	0.320		165	not stated; modified itt; registry:outcomes
26	A3 vs A1	md	5.10 kg		4.28 to 5.91		not stated; modified itt; registry:outcomes

HbA1c below 7 percent (8 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	responders	58.8		160	not stated; modified itt; registry:outcomes
26	A1	responders	58.6		157	not stated; modified itt; R0024240:Table 3
26	A1 vs A2	rd	30.9	20 to 41		not stated; modified itt; R0024240:Table 3
26	A1 vs A3	rd	15.2	4 to 26		not stated; modified itt; R0024240:Table 3
26	A2	responders	30.7		166	not stated; modified itt; registry:outcomes
26	A2	responders	27.7		155	not stated; modified itt; R0024240:Table 3
26	A3	responders	43.6		165	not stated; modified itt; registry:outcomes
26	A3	responders	43.4		159	not stated; modified itt; R0024240:Table 3

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

Arm	Statistic	Estimate	Events / N	Detail
A1	events		0 / 160	not stated; modified itt; R0026900:Research design and methods
A1	events	1.3	160	not stated; modified itt; R0026900:Research design and methods
A2	events	3.0	166	not stated; modified itt; R0026900:Research design and methods
A2	events		0 / 166	not stated; modified itt; R0026900:Research design and methods
A3	events		0 / 165	not stated; modified itt; R0026900:Research design and methods
A3	events	0.6	165	not stated; modified itt; R0026900:Research design and methods

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

Arm	Statistic	Estimate	SE or SD	Detail
A1	rate	0.03	0.021	not stated; modified itt; registry:outcomes
A2	rate	0.12	0.039	not stated; modified itt; registry:outcomes
A3	rate	0.01	0.014	not stated; modified itt; registry:outcomes

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-3.6 mmHg	0.97		160	not stated; modified itt; registry:outcomes
26	A2	change	0.2 mmHg	0.95		163	not stated; modified itt; registry:outcomes
26	A2 vs A1	md	3.8 mmHg		1.3 to 6.3		not stated; modified itt; registry:outcomes
26	A3	change	-1.6 mmHg	0.95		165	not stated; modified itt; registry:outcomes
26	A3 vs A1	md	2.0 mmHg		-0.5 to 4.5		not stated; modified itt; registry:outcomes

Acute kidney injury (3 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 160	not stated; safety; renal failure acute; registry:adverse_events
A2	events	0 / 166	not stated; safety; renal failure acute; registry:adverse_events
A3	events	1 / 165	not stated; safety; renal failure acute; registry:adverse_events

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	6.78 points	1.35	4.11 to 9.44	133	not stated; modified itt; R0026900:Table 2
26	A2	change	5.81 points	1.33	3.20 to 8.42	141	not stated; modified itt; R0026900:Table 2
26	A3	change	2.00 points	1.38	-0.71 to 4.71	131	not stated; modified itt; R0026900:Table 2

Health related quality of life total score (any instrument) (9 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	3.96 points	0.60	2.78 to 5.15	121	not stated; modified itt; R0026900:Table 2
26	A1	change	0.04 points	0.02	0.01 to 0.08	129	not stated; modified itt; R0026900:Table 2
26	A1	change	5.15 points	1.04	3.11 to 7.19	132	not stated; modified itt; R0026900:Table 2
26	A2	change	2.35 points	0.59	1.19 to 3.51	127	not stated; modified itt; R0026900:Table 2
26	A2	change	0.05 points	0.02	0.02 to 0.08	139	not stated; modified itt; R0026900:Table 2
26	A2	change	4.56 points	1.02	2.56 to 6.57	139	not stated; modified itt; R0026900:Table 2
26	A3	change	2.50 points	0.61	1.31 to 3.69	123	not stated; modified itt; R0026900:Table 2
26	A3	change	0.02 points	0.02	-0.01 to 0.06	130	not stated; modified itt; R0026900:Table 2
26	A3	change	1.20 points	1.06	-0.87 to 3.28	130	not stated; modified itt; R0026900:Table 2

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	4 / 160	not stated; safety; registry:adverse_events
A2	events	5 / 166	not stated; safety; registry:adverse_events
A3	events	10 / 165	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	11 / 170	not stated; randomized; registry:flow
A2	events	5 / 172	not stated; randomized; registry:flow
A3	events	7 / 172	not stated; randomized; registry:flow

Nausea (6 lines; O27A)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	24	160	not stated; modified itt; R0024240:Table 4
A1	events		38 / 160	not stated; safety; registry:adverse_events
A2	events	10	166	not stated; modified itt; R0024240:Table 4
A2	events		16 / 166	not stated; safety; registry:adverse_events
A3	events	5	165	not stated; modified itt; R0024240:Table 4
A3	events		8 / 165	not stated; safety; registry:adverse_events

Vomiting (6 lines; O27B)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	11	160	not stated; modified itt; R0024240:Table 4
A1	events		18 / 160	not stated; safety; registry:adverse_events
A2	events	2	166	not stated; modified itt; R0024240:Table 4
A2	events		4 / 166	not stated; safety; registry:adverse_events
A3	events	3	165	not stated; modified itt; R0024240:Table 4
A3	events		5 / 165	not stated; safety; registry:adverse_events

Diarrhea (6 lines; O27C)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	18	160	not stated; modified itt; R0024240:Table 4
A1	events		29 / 160	not stated; safety; registry:adverse_events
A2	events	10	166	not stated; modified itt; R0024240:Table 4
A2	events		16 / 166	not stated; safety; registry:adverse_events
A3	events	7	165	not stated; modified itt; R0024240:Table 4
A3	events		12 / 165	not stated; safety; registry:adverse_events

Constipation (6 lines; O27D)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	6	160	not stated; modified itt; R0024240:Table 4
A1	events		9 / 160	not stated; safety; registry:adverse_events
A2	events	2	166	not stated; modified itt; R0024240:Table 4
A2	events		3 / 166	not stated; safety; registry:adverse_events
A3	events	1	165	not stated; modified itt; R0024240:Table 4
A3	events		2 / 165	not stated; safety; registry:adverse_events

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

Arm	Statistic	Events / N	Detail
A1	events	1 / 160	not stated; modified itt; nausea; R0026900:Research design and methods
A2	events	1 / 166	not stated; modified itt; nausea; R0026900:Research design and methods
A3	events	1 / 165	not stated; modified itt; nausea; R0026900:Research design and methods

Gallbladder and biliary disease (6 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 160	not stated; safety; bile duct obstruction; registry:adverse_events
A1	events	0 / 160	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	0 / 166	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	0 / 166	not stated; safety; bile duct obstruction; registry:adverse_events
A3	events	1 / 165	not stated; safety; bile duct obstruction; registry:adverse_events
A3	events	1 / 165	not stated; safety; cholelithiasis; registry:adverse_events

Acute pancreatitis (6 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 160	not stated; safety; pancreatitis necrotising; registry:adverse_events
A1	events	0 / 160	not stated; safety; pancreatitis; registry:adverse_events
A2	events	0 / 166	not stated; safety; pancreatitis necrotising; registry:adverse_events
A2	events	0 / 166	not stated; safety; pancreatitis; registry:adverse_events
A3	events	1 / 165	not stated; safety; pancreatitis necrotising; registry:adverse_events
A3	events	1 / 165	not stated; safety; pancreatitis; registry:adverse_events

Thyroid cancer (any) (3 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 160	not stated; safety; papillary thyroid cancer; registry:adverse_events
A2	events	1 / 166	not stated; safety; papillary thyroid cancer; registry:adverse_events
A3	events	0 / 165	not stated; safety; papillary thyroid cancer; registry:adverse_events