parallel randomized trial

NCT00676338

Safety and Efficacy of Exenatide Once Weekly Injection Versus Metformin, Dipeptidyl Peptidase-4 Inhibitor, or Thiazolidinedione as Monotherapy in Drug-Naive Patients With Type 2 Diabetes

Type 2 diabetes (adults)NCT00676338S001966

Design

Randomized: 820
Start year: 2008
Treatment: 26 weeks, follow-up 36 weeks
Countries: multinational
Sponsor: Amylin Pharmaceuticals and Eli Lilly (industry)
Eligibility: adults, HbA1c 7.1 to 11.0 percent, BMI 23 to 45 kg/m2, drug naive

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 extended release 2 mg subcutaneous once weekly Exenatide once weekly 2 mg plus oral placebo	lifestyle: standard	248	218	210
A2	Metformin Metformin plus SC placebo	lifestyle: standard	246	218	213
A3	Pioglitazone Pioglitazone 45 mg/day plus SC placebo	lifestyle: standard	163	137	133
A4	Sitagliptin Sitagliptin 100 mg/day plus SC placebo	lifestyle: standard	163	142	140

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	Metformin A2	Pioglitazone A3	Sitagliptin A4
age: 18 to 65	n	217	215	135	144
age: 65 or older	n	31	31	28	19
age	mean (years)	54	54	55	52
age	sd (years)	11	11	11	11
black	n	7	11	4	3
black	percent	2.8	4.5	2.5	1.8
bmi	mean (kg/m2)	31.4	30.7	31.1	31.8
bmi	sd (kg/m2)	5.3	5.5	5.3	5.4
diabetes duration	mean (years)	2.7	2.6	2.7	2.7
diabetes duration	sd (years)	3.2	3.6	3.7	3.7
female	n	109	92	66	69
female	percent	44.0	37.4	40.5	42.3
hba1c	mean (percent)	8.5	8.6	8.5	8.5
hba1c	sd (percent)	1.2	1.2	1.2	1.3
hispanic	n	16	21	15	13
hispanic	percent	6.5	8.5	9.2	8.0
other race east asian	n	34	31	19	18
other race east asian	percent	13.7	12.6	11.7	11.0
other race other	n	1	3	0	1
other race other	percent	0.4	1.2	0	0.6
other race west asian	n	21	20	15	15
other race west asian	percent	8.5	8.1	9.2	9.2
sbp	mean (mmHg)	129	129	131	130
sbp	sd (mmHg)	12	15	15	13
weight	mean (kg)	87.5	85.9	86.1	88.7
weight	sd (kg)	18.9	19.6	17.8	18.7
white	n	169	160	110	113
white	percent	68.1	65.0	67.5	69.3

Analyses this trial contributes to

Results

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

HbA1c change (11 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.56 percent	0.07			not stated; full analysis; R0027761:Results
26	A1 vs A3	md	0.10 percent	0.10	-0.15 to 0.35		not stated; full analysis; registry:outcomes
26	A1 vs A4	md	-0.37 percent	0.10	-0.62 to -0.13		not stated; full analysis; registry:outcomes
26	A1	change	-1.53 percent	0.07		218	not stated; full analysis; R0027761:Results
26	A1 vs A2	md	-0.05 percent	0.09	-0.26 to 0.17		not stated; full analysis; registry:outcomes
26	A2	change	-1.52 percent	0.06			not stated; full analysis; R0027761:Results
26	A2	change	-1.48 percent	0.07		218	not stated; full analysis; R0027761:Results
26	A3	change	-1.73 percent	0.08			not stated; full analysis; R0027761:Results
26	A3	change	-1.63 percent	0.08		137	not stated; full analysis; R0027761:Results
26	A4	change	-1.15 percent	0.08		142	not stated; full analysis; R0027761:Results
26	A4	change	-1.17 percent	0.08			not stated; full analysis; R0027761:Results

Body weight change in kilograms (diabetes) (7 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A2	md	-0.04 kg	0.29	-0.61 to 0.53		not stated; full analysis; registry:outcomes
26	A1 vs A4	md	-1.28 kg	0.33	-1.92 to -0.63		not stated; full analysis; registry:outcomes
26	A1	change	-2.0 kg	0.2		215	not stated; full analysis; R0027761:Results
26	A1 vs A3	md	-3.56 kg	0.33	-4.21 to -2.90		not stated; full analysis; registry:outcomes
26	A2	change	-2.0 kg	0.2		217	not stated; full analysis; R0027761:Results
26	A3	change	1.5 kg	0.3		134	not stated; full analysis; R0027761:Results
26	A4	change	-0.8 kg	0.3		141	not stated; full analysis; R0027761:Results

HbA1c below 7 percent (15 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1 vs A2	rd	6.8	-2 to 15		not stated; other; R0024240:Table 3
26	A1 vs A4	rd	20.2	10 to 30		not stated; other; R0024240:Table 3
26	A1	responders	61.6		237	not stated; other; R0024240:Table 3
26	A1	responders	63			not stated; other; R0027761:Figure 2
26	A1	responders	64.2		226	not stated; other; registry:outcomes
26	A1 vs A3	rd	3.0	-7 to 13		not stated; other; R0024240:Table 3
26	A2	responders	54.8		239	not stated; other; R0024240:Table 3
26	A2	responders	55			not stated; other; R0027761:Figure 2
26	A2	responders	57.3		232	not stated; other; registry:outcomes
26	A3	responders	58.5		157	not stated; other; R0024240:Table 3
26	A3	responders	61			not stated; other; R0027761:Figure 2
26	A3	responders	63.3		150	not stated; other; registry:outcomes
26	A4	responders	43			not stated; other; R0027761:Figure 2
26	A4	responders	45.5		143	not stated; other; registry:outcomes
26	A4	responders	41.4		152	not stated; other; R0024240:Table 3

Level 2 or 3 hypoglycemia (participants) (12 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	5 / 248	not stated; full analysis; R0027761:Results
A1	events	0 / 248	not stated; full analysis; R0027761:Results
A1	events	13 / 248	not stated; full analysis; R0027761:Results
A2	events	10 / 246	not stated; full analysis; R0027761:Results
A2	events	0 / 246	not stated; full analysis; registry:outcomes
A2	events	0 / 246	not stated; full analysis; R0027761:Results
A3	events	0 / 163	not stated; full analysis; registry:outcomes
A3	events	6 / 163	not stated; full analysis; R0027761:Results
A3	events	0 / 163	not stated; full analysis; R0027761:Results
A4	events	0 / 163	not stated; full analysis; R0027761:Results
A4	events	5 / 163	not stated; full analysis; R0027761:Results
A4	events	0 / 163	not stated; full analysis; registry:outcomes

Systolic blood pressure change (7 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A2	md	-1.39 mmHg	1.09	-3.52 to 0.74		not stated; full analysis; registry:outcomes
26	A1 vs A4	md	0.56 mmHg	1.22	-1.84 to 2.96		not stated; full analysis; registry:outcomes
26	A1	change	-1.3 mmHg	0.8		215	not stated; full analysis; R0027761:Results
26	A1 vs A3	md	0.49 mmHg	1.24	-1.94 to 2.93		not stated; full analysis; registry:outcomes
26	A2	change	0.14 mmHg	0.78		217	not stated; full analysis; registry:outcomes
26	A3	change	-1.7 mmHg	1.0		134	not stated; full analysis; R0027761:Results
26	A4	change	-1.8 mmHg	1.0		141	not stated; full analysis; R0027761:Results

All cause mortality (1 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	events				1 / 246	not stated; full analysis; R0027761:Results

Health related quality of life total score (any instrument) (35 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A2	md	0.00 points		-0.02 to 0.02		not stated; other; R0027761:Supplement Table 9
26	A1	change	3.38 points	0.40		222	not stated; other; R0027761:Supplement Table 7
26	A1	change	0.03 points	0.01		232	not stated; other; R0027761:Supplement Table 8
26	A1	change	0.02 points	0.01		232	not stated; other; R0027761:Supplement Table 9
26	A1	change	4.85 points	0.77		228	not stated; other; R0027761:Supplement Table 4
26	A1	final	13.08 points			221	not stated; other; R0027761:Supplement Table 6
26	A1 vs A2	md	0.65 points		-0.48 to 1.78		not stated; other; R0027761:Supplement Table 6
26	A1 vs A2	md	0.43 points		-0.62 to 1.49		not stated; other; R0027761:Supplement Table 7
26	A1 vs A2	md	0.00 points		-0.02 to 0.03		not stated; other; R0027761:Supplement Table 8
26	A1 vs A2	md	0.01 points		-2.02 to 2.04		not stated; other; R0027761:Supplement Table 4
26	A1 vs A3	md	-0.27 points		-1.55 to 1.01		not stated; other; R0027761:Supplement Table 6
26	A1 vs A3	md	-0.32 points		-1.51 to 0.88		not stated; other; R0027761:Supplement Table 7
26	A1 vs A3	md	0.04 points		0.01 to 0.07		not stated; other; R0027761:Supplement Table 8
26	A1 vs A3	md	0.03 points		0.00 to 0.05		not stated; other; R0027761:Supplement Table 9
26	A1 vs A3	md	3.54 points		1.23 to 5.84		not stated; other; R0027761:Supplement Table 4
26	A1 vs A4	md	0.59 points		-0.70 to 1.87		not stated; other; R0027761:Supplement Table 6
26	A1 vs A4	md	0.77 points		-0.41 to 1.95		not stated; other; R0027761:Supplement Table 7
26	A1 vs A4	md	0.02 points		-0.02 to 0.05		not stated; other; R0027761:Supplement Table 8
26	A1 vs A4	md	0.01 points		-0.01 to 0.03		not stated; other; R0027761:Supplement Table 9
26	A1 vs A4	md	0.83 points		-1.48 to 3.13		not stated; other; R0027761:Supplement Table 4
26	A2	change	4.84 points	0.77		221	not stated; other; R0027761:Supplement Table 4
26	A2	final	12.42 points			224	not stated; other; R0027761:Supplement Table 6
26	A2	change	2.95 points	0.40		210	not stated; other; R0027761:Supplement Table 7
26	A2	change	0.03 points	0.01		227	not stated; other; R0027761:Supplement Table 8
26	A2	change	0.02 points	0.01		227	not stated; other; R0027761:Supplement Table 9
26	A3	change	-0.01 points	0.01		146	not stated; other; R0027761:Supplement Table 9
26	A3	final	13.35 points			143	not stated; other; R0027761:Supplement Table 6
26	A3	change	3.70 points	0.49		138	not stated; other; R0027761:Supplement Table 7
26	A3	change	-0.01 points	0.01		146	not stated; other; R0027761:Supplement Table 8
26	A3	change	1.31 points	0.94		142	not stated; other; R0027761:Supplement Table 4
26	A4	change	0.01 points	0.01		149	not stated; other; R0027761:Supplement Table 9
26	A4	final	12.49 points			140	not stated; other; R0027761:Supplement Table 6
26	A4	change	2.61 points	0.48		143	not stated; other; R0027761:Supplement Table 7
26	A4	change	0.02 points	0.01		149	not stated; other; R0027761:Supplement Table 8
26	A4	change	4.02 points	0.95		142	not stated; other; R0027761:Supplement Table 4

Serious adverse events (5 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	4 / 248	not stated; full analysis; R0027761:Results
A2	events	12 / 246	not stated; safety; registry:adverse_events
A2	events	13 / 246	not stated; full analysis; R0027761:Results
A3	events	9 / 163	not stated; full analysis; R0027761:Results
A4	events	3 / 163	not stated; full analysis; R0027761:Results

Discontinuation due to adverse events (8 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	6 / 248	not stated; randomized; registry:flow
A1	events	6 / 248	not stated; randomized; R0027761:Figure 1
A2	events	6 / 246	not stated; randomized; R0027761:Figure 1
A2	events	6 / 246	not stated; randomized; registry:flow
A3	events	5 / 163	not stated; randomized; registry:flow
A3	events	5 / 163	not stated; randomized; R0027761:Figure 1
A4	events	1 / 163	not stated; randomized; R0027761:Figure 1
A4	events	1 / 163	not stated; randomized; registry:flow

Nausea (9 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	28 / 248	not stated; full analysis; R0027761:Table 1
A1	events	0 / 248	not stated; safety; registry:adverse_events
A2	events	0 / 246	not stated; safety; registry:adverse_events
A2	events	17 / 246	not stated; full analysis; R0027761:Table 1
A3	events	7 / 163	not stated; full analysis; R0027761:Table 1
A3	events	1 / 163	not stated; safety; registry:adverse_events
A3	events	6 / 163	not stated; safety; registry:adverse_events
A4	events	6 / 163	not stated; full analysis; R0027761:Table 1
A4	events	0 / 163	not stated; safety; registry:adverse_events

Vomiting (8 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	12 / 248	not stated; full analysis; R0027761:Results
A1	events	0 / 248	not stated; safety; registry:adverse_events
A2	events	0 / 246	not stated; safety; registry:adverse_events
A2	events	8 / 246	not stated; full analysis; R0027761:Results
A3	events	5 / 163	not stated; full analysis; R0027761:Results
A3	events	1 / 163	not stated; safety; registry:adverse_events
A4	events	0 / 163	not stated; safety; registry:adverse_events
A4	events	3 / 163	not stated; full analysis; R0027761:Results

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	27 / 248	not stated; full analysis; R0027761:Table 1
A2	events	31 / 246	not stated; full analysis; R0027761:Table 1
A3	events	6 / 163	not stated; full analysis; R0027761:Table 1
A4	events	9 / 163	not stated; full analysis; R0027761:Table 1

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	21 / 248	not stated; full analysis; R0027761:Table 1
A2	events	8 / 246	not stated; full analysis; R0027761:Table 1
A3	events	3 / 163	not stated; full analysis; R0027761:Table 1
A4	events	4 / 163	not stated; full analysis; R0027761:Table 1

Discontinuation due to gastrointestinal adverse events (1 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 248	not stated; full analysis; nausea; R0027761:Results