parallel randomized trial

AWARD-8

A Randomized, Parallel-Arm, Double-Blinded Study Comparing the Effect of Once-Weekly Dulaglutide With Placebo in Patients With Type 2 Diabetes Mellitus on Sulfonylurea Therapy (AWARD-8: Assessment of Weekly AdministRation of LY2189265 in Diabetes - 8)

Type 2 diabetes (adults)NCT01769378S001068

Design

Randomized: 300
Start year: 2013
Treatment: 24 weeks, follow-up 28.29 weeks
Countries: Argentina, Austria, Romania, United States, South Africa, Mexico, Slovenia, Croatia, Puerto Rico
Sponsor: Eli Lilly and Company (industry)
Eligibility: age 18 or older; BMI up to 45; HbA1c 7.5 to 9.5 percent on sulfonylurea at least half maximal dose

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: yes
Primary estimand: hypothetical
Analysis population: modified itt
Missing data: MMRM with values after rescue censored

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Dulaglutide 1.5 mg subcutaneous once weekly Dulaglutide 1.5 mg	glimepiride at stable lead in dose; lifestyle: not reported	240	239	215
A2	Placebo Placebo	glimepiride at stable lead in dose; lifestyle: not reported	60	60	56

Baseline characteristics

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

Characteristic	Statistic	Dulaglutide 1.5 mg subcutaneous once weekly A1	Placebo A2
age	mean (years)	57.7	58.2
age	sd (years)	10.2	7.4
asian	n	3	2
asian	percent	1.3	3.3
black	n	7	4
black	percent	2.9	6.7
bmi	mean (kg/m2)	30.9	32.4
bmi	sd (kg/m2)	5.2	5.9
diabetes duration	mean (years)	7.8	6.8
diabetes duration	sd (years)	5.3	3.8
egfr	mean (mL/min)	90.2	88.0
egfr	sd (mL/min)	18.3	17.4
female	n	135	32
female	percent	56.5	53.3
hba1c	mean (percent)	8.4	8.4
hba1c	sd (percent)	0.7	0.7
hispanic	n	112	27
hispanic	percent	46.9	45.0
other race american indian alaska native	n	21	5
other race american indian alaska native	percent	8.8	8.3
other race multiple	n	6	2
other race multiple	percent	2.5	3.3
sbp	mean (mmHg)	132	130
sbp	sd (mmHg)	13	12
weight	mean (kg)	84.5	89.5
weight	sd (kg)	16.4	18.6
white	n	202	47
white	percent	84.5	78.3

Analyses this trial contributes to

Results

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

HbA1c change (20 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
24	A1 vs A2	md	-1.3 percent		-1.6 to -1.0		hypothetical; modified itt; R0016038:Results
24	A1	change	-1.54 percent		-1.79 to -1.29	104	not stated; modified itt; hba1c:8.5_or_more; R0014882:Supplement Table 3
24	A1 vs A2	md	-1.27 percent		-1.57 to -0.97		hypothetical; modified itt; registry:outcomes
24	A1	change	-1.19 percent		-1.41 to -0.97	132	not stated; modified itt; hba1c:less_than_8.5; R0014882:Supplement Table 3
24	A1	change	-1.38 percent	0.08		215	hypothetical; modified itt; registry:outcomes
24	A1	change	-1.41 percent		-1.62 to -1.19	134	not stated; modified itt; sex:female; R0014882:Supplement Table 3
24	A1	change	-1.4 percent				hypothetical; modified itt; R0016038:Results
24	A1	change	-1.27 percent		-1.51 to -1.02	102	not stated; modified itt; sex:male; R0014882:Supplement Table 3
24	A1	change	-1.40 percent		-1.65 to -1.16	87	not stated; modified itt; diabetes_duration:5_to_less_than_10; R0014882:Supplement Table 3
24	A1	change	-1.04 percent		-1.32 to -0.77	75	not stated; modified itt; diabetes_duration:10_or_more; R0014882:Supplement Table 3
24	A1	change	-1.47 percent		-1.74 to -1.20	74	not stated; modified itt; diabetes_duration:less_than_5; R0014882:Supplement Table 3
24	A2	change	-0.1 percent				hypothetical; modified itt; R0016038:Results
24	A2	change	-0.11 percent	0.14		53	hypothetical; modified itt; registry:outcomes
24	A2	change	0.03 percent		-0.52 to 0.58		not stated; modified itt; diabetes_duration:10_or_more; R0014882:Supplement Table 3
24	A2	change	0.29 percent		-0.12 to 0.70		not stated; modified itt; diabetes_duration:5_to_less_than_10; R0014882:Supplement Table 3
24	A2	change	-0.62 percent		-1.09 to -0.16		not stated; modified itt; diabetes_duration:less_than_5; R0014882:Supplement Table 3
24	A2	change	-0.24 percent		-0.65 to 0.16		not stated; modified itt; hba1c:8.5_or_more; R0014882:Supplement Table 3
24	A2	change	0.04 percent		-0.35 to 0.42		not stated; modified itt; hba1c:less_than_8.5; R0014882:Supplement Table 3
24	A2	change	0.07 percent		-0.31 to 0.45		not stated; modified itt; sex:female; R0014882:Supplement Table 3
24	A2	change	-0.30 percent		-0.70 to 0.11		not stated; modified itt; sex:male; R0014882:Supplement Table 3

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
24	A1	change	-0.91 kg	0.21		212	hypothetical; modified itt; R0016038:Results
24	A1 vs A2	md	-0.68 kg	0.43	-1.53 to 0.18		hypothetical; modified itt; R0016038:Results
24	A1	change	-0.24 kg		-0.91 to 0.43	102	not stated; modified itt; sex:male; R0014882:Table 2
24	A1	change	-0.64 kg		-1.38 to 0.11	75	not stated; modified itt; diabetes_duration:10_or_more; R0014882:Table 2
24	A1	change	-0.75 kg		-1.35 to -0.16	134	not stated; modified itt; sex:female; R0014882:Table 2
24	A1	change	-0.56 kg		-1.25 to 0.12	87	not stated; modified itt; diabetes_duration:5_to_less_than_10; R0014882:Table 2
24	A1	change	-0.62 kg		-1.20 to -0.03	132	not stated; modified itt; hba1c:less_than_8.5; R0014882:Table 2
24	A1	change	-0.46 kg		-1.22 to 0.30	74	not stated; modified itt; diabetes_duration:less_than_5; R0014882:Table 2
24	A1	change	-0.49 kg		-1.15 to 0.18	104	not stated; modified itt; hba1c:8.5_or_more; R0014882:Table 2
24	A2	change	0.54 kg		-0.58 to 1.65		not stated; modified itt; sex:male; R0014882:Table 2
24	A2	change	-0.24 kg	0.40		53	hypothetical; modified itt; R0016038:Results
24	A2	change	-0.39 kg		-1.93 to 1.15		not stated; modified itt; diabetes_duration:10_or_more; R0014882:Table 2
24	A2	change	-0.09 kg		-1.21 to 1.03		not stated; modified itt; diabetes_duration:5_to_less_than_10; R0014882:Table 2
24	A2	change	0.47 kg		-0.84 to 1.78		not stated; modified itt; diabetes_duration:less_than_5; R0014882:Table 2
24	A2	change	-0.20 kg		-1.26 to 0.86		not stated; modified itt; hba1c:8.5_or_more; R0014882:Table 2
24	A2	change	0.18 kg		-0.86 to 1.21		not stated; modified itt; hba1c:less_than_8.5; R0014882:Table 2
24	A2	change	-0.39 kg		-1.39 to 0.61		not stated; modified itt; sex:female; R0014882:Table 2

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
24	A1	responders	55.3		215	hypothetical; modified itt; R0016038:Results
24	A1 vs A2	or	11.37	3.82 to 33.84		hypothetical; modified itt; registry:outcomes
24	A2	responders	18.9		53	hypothetical; modified itt; R0016038:Results

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

Arm	Statistic	Events / N	Detail
A1	events	50 / 239	hypothetical; modified itt; R0016038:Table 3
A1	events	13 / 239	hypothetical; modified itt; R0016038:Supplement Table S3
A1	events	0 / 239	hypothetical; modified itt; R0016038:Table 3
A2	events	2 / 60	hypothetical; modified itt; R0016038:Table 3
A2	events	0 / 60	hypothetical; modified itt; R0016038:Supplement Table S3
A2	events	0 / 60	hypothetical; modified itt; R0016038:Table 3

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Detail
24	A1	change	-0.52 mmHg	0.96		not stated; modified itt; R0016038:Table 2
24	A1 vs A2	md	0.3 mmHg		-3.2 to 3.3	not stated; other; R0008191:Supplement Table S4
24	A2	change	0.00 mmHg	1.54		not stated; modified itt; R0016038:Table 2

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 239	not stated; modified itt; R0016038:Results
	A2	events				0 / 60	not stated; modified itt; R0016038:Results

Three point MACE (2 lines; O21)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 239	not stated; modified itt; cerebrovascular accident; R0016038:Supplement Table S2
	A2	events				0 / 60	not stated; modified itt; cerebrovascular accident; R0016038:Supplement Table S2

Hospitalization for heart failure (2 lines; O23)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 239	not stated; modified itt; R0016038:Results
	A2	events				0 / 60	not stated; modified itt; registry:outcomes

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 239	not stated; modified itt; R0016038:Table 2
	A2	events				0 / 60	not stated; modified itt; R0016038:Table 2

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	10 / 240	not stated; randomized; R0016038:Figure 1
A1	events	10 / 240	not stated; randomized; registry:flow
A2	events	0 / 60	not stated; randomized; R0016038:Figure 1
A2	events	0 / 60	not stated; randomized; registry:flow

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				25 / 239	not stated; modified itt; R0016038:Table 2
	A2	events				0 / 60	not stated; modified itt; R0016038:Table 2

Vomiting (1 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				10 / 239	not stated; modified itt; R0016038:Results

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				20 / 239	not stated; modified itt; R0016038:Table 2
	A2	events				0 / 60	not stated; modified itt; R0016038:Table 2

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 239	not stated; modified itt; registry:outcomes
	A2	events				0 / 60	not stated; modified itt; registry:outcomes

Medullary thyroid carcinoma (2 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 239	not stated; modified itt; R0016038:Results
	A2	events				0 / 60	not stated; modified itt; R0016038:Results

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 239	not stated; modified itt; R0016038:Results
	A2	events				0 / 60	not stated; modified itt; R0016038:Results