parallel randomized trial

AWARD-7

A Randomized, Open-Label, Parallel-Arm Study Comparing the Effect of Once-weekly Dulaglutide With Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes and Moderate or Severe Chronic Kidney Disease

Type 2 diabetes (adults)Chronic kidney disease with diabetes NCT01621178S000237

Design

Randomized: 577
Start year: 2012
Treatment: 52 weeks, follow-up 56 weeks
Countries: Brazil, Hungary, Mexico, Poland, Romania, South Africa, Spain, Ukraine, United States (99 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: adults with T2D and CKD stage 3 to 4 (eGFR 15 to below 60); HbA1c 7.5 to 10.5 percent on insulin; maximal ACEI or ARB; BMI 23 to 45

Conduct and analysis

Blinding: single blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: hypothetical
Analysis population: modified itt
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Insulin glargine Insulin glargine plus insulin lispro	insulin lispro with 3 largest meals titrated to premeal glucose 120 to 180 mg/dL; ACEI or ARB; lifestyle: not reported	194	186	163
A2	Dulaglutide 0.75 mg subcutaneous once weekly Dulaglutide 0.75 mg plus insulin lispro	insulin lispro with 3 largest meals titrated to premeal glucose 120 to 180 mg/dL; ACEI or ARB; lifestyle: not reported	190	180	160
A3	Dulaglutide 1.5 mg subcutaneous once weekly Dulaglutide 1.5 mg plus insulin lispro	insulin lispro with 3 largest meals titrated to premeal glucose 120 to 180 mg/dL; ACEI or ARB; lifestyle: not reported	193	183	157

Baseline characteristics

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

Characteristic	Statistic	Insulin glargine A1	Dulaglutide 0.75 mg subcutaneous once weekly A2	Dulaglutide 1.5 mg subcutaneous once weekly A3
age	mean (years)	64.3	64.7	64.7
age	sd (years)	8.4	8.6	8.8
asian	n	5	4	7
asian	percent	3	2	4
black	n	26	36	26
black	percent	14	19	14
bmi	mean (kg/m2)	32.4	33.0	32.1
bmi	sd (kg/m2)	5.3	5.5	4.8
diabetes duration	mean (years)	18.7	18.0	17.6
diabetes duration	sd (years)	8.7	8.8	8.7
egfr: 15 to less than 30	n	61	55	55
egfr: 15 to less than 30	percent	31	29	29
egfr: 30 to less than 45	n	67	75	73
egfr: 30 to less than 45	percent	35	39	38
egfr: 45 to less than 60	n	51	53	53
egfr: 45 to less than 60	percent	26	28	28
egfr: 60 to less than 90	n	14	7	9
egfr: 60 to less than 90	percent	7	4	5
egfr: less than 15	n	1	0	2
egfr: less than 15	percent	1	0	1
egfr	mean (mL/min/1.73 m2)	38.5	38.3	38.1
egfr	sd (mL/min/1.73 m2)	13.0	12.3	13.2
established cvd	n	48		51
established cvd	percent	38.4		41.1
female	n	101	86	88
female	percent	52	45	46
hba1c: more than 8.5	n	81	91	96
hba1c: more than 8.5	percent	42	48	50
hba1c	mean (percent)	8.6	8.6	8.6
hba1c	sd (percent)	1.0	1.1	0.9
hispanic	n	79	75	78
hispanic	percent	41	39	41
insulin dose	mean (U/day)	59.3	56.6	58.8
insulin dose	sd (U/day)	34.2	31.2	30.1
other race american indian alaska native	n	18	17	12
other race american indian alaska native	percent	9	9	6
other race multiple	n	6	7	10
other race multiple	percent	3	4	5
other race native hawaiian pacific islander	n	1	0	0
other race native hawaiian pacific islander	percent	1	0	0
other race unknown	n	1	4	3
sbp	mean (mmHg)	136.7	137.4	136.8
sbp	sd (mmHg)	14.3	14.9	13.7
uacr: 30 to 300	n	56	61	74
uacr: 30 to 300	percent	29	32	39
uacr: less than 30	n	48	44	34
uacr: less than 30	percent	25	23	18
uacr: more than 300	n	90	84	84
uacr: more than 300	percent	46	44	44
uacr	median (mg/g)	195.6	233.6	213.7
uacr	q1 (mg/g)	30.1	36.7	45.8
uacr	q3 (mg/g)	1015.1	946.5	868.0
weight	mean (kg)	88.2	90.9	88.1
weight	sd (kg)	18.5	18.3	16.0
white	n	137	122	134
white	percent	71	66	71

Analyses this trial contributes to

Results

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

HbA1c change (10 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.1 percent	0.1		175	hypothetical; modified itt; R0017387:Results
26	A2	change	-1.1 percent	0.1		149	hypothetical; modified itt; R0017387:Results
26	A2 vs A1	md	0.02 percent		-0.18 to 0.22		hypothetical; modified itt; R0017387:Figure 2A
26	A3	change	-1.2 percent	0.1		138	hypothetical; modified itt; R0017387:Results
26	A3 vs A1	md	-0.05 percent		-0.26 to 0.15		hypothetical; modified itt; R0017387:Figure 2A
52	A1	change	-1.0 percent	0.1		153	hypothetical; modified itt; R0017387:Abstract
52	A2	change	-1.1 percent	0.1		132	hypothetical; modified itt; R0017387:Abstract
52	A2 vs A1	md	-0.10 percent		-0.33 to 0.13		hypothetical; modified itt; R0017387:Supplement Table 4
52	A3	change	-1.1 percent	0.1		130	hypothetical; modified itt; R0017387:Abstract
52	A3 vs A1	md	-0.10 percent		-0.34 to 0.14		hypothetical; modified itt; R0017387:Supplement Table 4

Body weight change in kilograms (diabetes) (10 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	1.1 kg	0.3		175	hypothetical; safety; R0017387:Supplement Table 4
26	A2	change	-2.0 kg	0.4		151	hypothetical; safety; R0017387:Supplement Table 4
26	A2 vs A1	md	-3.13 kg		-3.92 to -2.34		hypothetical; safety; R0017387:Supplement Table 4
26	A3	change	-2.8 kg	0.4		140	hypothetical; safety; R0017387:Supplement Table 4
26	A3 vs A1	md	-3.92 kg		-4.73 to -3.11		hypothetical; safety; R0017387:Supplement Table 4
52	A1	change	1.6 kg	0.4		158	hypothetical; safety; R0017387:Supplement Table 4
52	A2	change	-1.7 kg	0.4		137	hypothetical; safety; R0017387:Supplement Table 4
52	A2 vs A1	md	-3.28 kg		-4.36 to -2.20		hypothetical; safety; R0017387:Supplement Table 4
52	A3	change	-2.7 kg	0.5		132	hypothetical; safety; R0017387:Supplement Table 4
52	A3 vs A1	md	-4.23 kg		-5.33 to -3.13		hypothetical; safety; R0017387:Supplement Table 4

HbA1c below 7 percent (6 lines; O03)

Week	Arm	Statistic	Estimate	Events / N	Detail
26	A1	responders	34.6	182	hypothetical; modified itt; R0017387:Supplement Figure 2B
26	A2	responders	31.7	164	hypothetical; modified itt; R0017387:Supplement Figure 2B
26	A3	responders	37.5	152	hypothetical; modified itt; R0017387:Supplement Figure 2B
52	A1	responders	29.1	182	hypothetical; modified itt; R0017387:Supplement Figure 2B
52	A2	responders	33.5	164	hypothetical; modified itt; R0017387:Supplement Figure 2B
52	A3	responders	32.9	152	hypothetical; modified itt; R0017387:Supplement Figure 2B

Level 2 or 3 hypoglycemia (participants) (30 lines; O04)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	4.1	194	hypothetical; safety; registry:outcomes
A1	events		145 / 194	hypothetical; safety; R0017387:Supplement Table 12
A1	events		16 / 194	treatment policy; safety; R0017387:Table 2
A1	events		13 / 194	hypothetical; safety; R0017387:Results
A1	events		123 / 194	hypothetical; safety; R0017387:Supplement Table 12
A1	events		13 / 194	not stated; safety; registry:adverse_events
A1	events	71.6	194	hypothetical; safety; registry:outcomes
A1	events	60.3	194	hypothetical; safety; registry:outcomes
A1	events	38.1	194	hypothetical; safety; registry:outcomes
A1	events		93 / 194	hypothetical; safety; R0017387:Supplement Table 12
A2	events		5 / 190	hypothetical; safety; R0017387:Results
A2	events	1.1	189	hypothetical; safety; registry:outcomes
A2	events	50.8	189	hypothetical; safety; registry:outcomes
A2	events	40.7	189	hypothetical; safety; registry:outcomes
A2	events	15.9	189	hypothetical; safety; registry:outcomes
A2	events		113 / 189	hypothetical; safety; R0017387:Supplement Table 12
A2	events		91 / 189	hypothetical; safety; R0017387:Supplement Table 12
A2	events		45 / 189	hypothetical; safety; R0017387:Supplement Table 12
A2	events		6 / 190	not stated; safety; registry:adverse_events
A2	events		9 / 190	treatment policy; safety; R0017387:Table 2
A3	events	31.6	190	hypothetical; safety; registry:outcomes
A3	events	13.2	190	hypothetical; safety; registry:outcomes
A3	events		77 / 190	hypothetical; safety; R0017387:Supplement Table 12
A3	events		39 / 190	hypothetical; safety; R0017387:Supplement Table 12
A3	events		0 / 192	hypothetical; safety; R0017387:Results
A3	events		95 / 190	hypothetical; safety; R0017387:Supplement Table 12
A3	events		1 / 192	not stated; safety; registry:adverse_events
A3	events	0	190	hypothetical; safety; registry:outcomes
A3	events	43.2	190	hypothetical; safety; registry:outcomes
A3	events		3 / 192	treatment policy; safety; R0017387:Table 2

Level 2 or 3 hypoglycemia (episode rate) (12 lines; O04B)

Arm	Statistic	Estimate	Events / N	Detail
A1	rate	9.6	194	hypothetical; safety; R0017387:Supplement Table 12
A1	rate	0.1	194	hypothetical; safety; R0017387:Supplement Table 12
A1	rate	14.4	194	hypothetical; safety; R0017387:Supplement Table 12
A1	rate	2.5	194	hypothetical; safety; R0017387:Supplement Table 12
A2	rate	0.8	189	hypothetical; safety; R0017387:Supplement Table 12
A2	rate	0.0	189	hypothetical; safety; R0017387:Supplement Table 12
A2	rate	7.6	189	hypothetical; safety; R0017387:Supplement Table 12
A2	rate	4.3	189	hypothetical; safety; R0017387:Supplement Table 12
A3	rate	0.7	190	hypothetical; safety; R0017387:Supplement Table 12
A3	rate	5.8	190	hypothetical; safety; R0017387:Supplement Table 12
A3	rate	4.4	190	hypothetical; safety; R0017387:Supplement Table 12
A3	rate	0.0	190	hypothetical; safety; R0017387:Supplement Table 12

Acute kidney injury (3 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	2 / 194	not stated; safety; registry:adverse_events
A2	events	5 / 190	not stated; safety; registry:adverse_events
A3	events	3 / 192	not stated; safety; registry:adverse_events

All cause mortality (6 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	6 / 194	treatment policy; safety; R0017387:Table 2
A1	events	6 / 194	treatment policy; safety; R0017387:Table 2
A2	events	9 / 190	treatment policy; safety; R0017387:Table 2
A2	events	7 / 190	treatment policy; safety; R0017387:Table 2
A3	events	3 / 192	treatment policy; safety; R0017387:Table 2
A3	events	2 / 192	treatment policy; safety; R0017387:Table 2

Four point MACE including unstable angina (3 lines; O21B)

Arm	Statistic	Events / N	Detail
A1	events	13 / 194	treatment policy; safety; R0017387:Table 2
A2	events	18 / 190	treatment policy; safety; R0017387:Table 2
A3	events	10 / 192	treatment policy; safety; R0017387:Table 2

Hospitalization for heart failure (9 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	2 / 194	not stated; safety; cardiac failure congestive; registry:adverse_events
A1	events	0 / 194	not stated; safety; cardiac failure acute; registry:adverse_events
A1	events	1 / 194	not stated; safety; cardiac failure; registry:adverse_events
A2	events	2 / 190	not stated; safety; cardiac failure congestive; registry:adverse_events
A2	events	1 / 190	not stated; safety; cardiac failure acute; registry:adverse_events
A2	events	1 / 190	not stated; safety; cardiac failure; registry:adverse_events
A3	events	0 / 192	not stated; safety; cardiac failure acute; registry:adverse_events
A3	events	2 / 192	not stated; safety; cardiac failure congestive; registry:adverse_events
A3	events	3 / 192	not stated; safety; cardiac failure; registry:adverse_events

Serious adverse events (6 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	52 / 194	treatment policy; safety; R0017387:Table 2
A1	events	56 / 194	not stated; safety; registry:adverse_events
A2	events	45 / 190	treatment policy; safety; R0017387:Table 2
A2	events	48 / 190	not stated; safety; registry:adverse_events
A3	events	38 / 192	treatment policy; safety; R0017387:Table 2
A3	events	41 / 192	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (12 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	5 / 194	not stated; randomized; registry:flow
A1	events	1 / 194	not stated; randomized; R0017387:Figure 1
A1	events	4 / 194	not stated; randomized; R0017387:Figure 1
A1	events	12 / 194	treatment policy; safety; R0017387:Table 2
A2	events	2 / 190	not stated; randomized; registry:flow
A2	events	19 / 190	treatment policy; safety; R0017387:Table 2
A2	events	1 / 190	not stated; randomized; R0017387:Figure 1
A2	events	1 / 190	not stated; randomized; R0017387:Figure 1
A3	events	24 / 192	treatment policy; safety; R0017387:Table 2
A3	events	7 / 193	not stated; randomized; R0017387:Figure 1
A3	events	8 / 193	not stated; randomized; registry:flow
A3	events	1 / 193	not stated; randomized; R0017387:Figure 1

Nausea (6 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 194	not stated; safety; registry:adverse_events
A1	events	9 / 194	treatment policy; safety; R0017387:Table 2
A2	events	1 / 190	not stated; safety; registry:adverse_events
A2	events	27 / 190	treatment policy; safety; R0017387:Table 2
A3	events	0 / 192	not stated; safety; registry:adverse_events
A3	events	38 / 192	treatment policy; safety; R0017387:Table 2

Vomiting (6 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	9 / 194	treatment policy; safety; R0017387:Table 2
A1	events	0 / 194	not stated; safety; registry:adverse_events
A2	events	1 / 190	not stated; safety; registry:adverse_events
A2	events	16 / 190	treatment policy; safety; R0017387:Table 2
A3	events	1 / 192	not stated; safety; registry:adverse_events
A3	events	26 / 192	treatment policy; safety; R0017387:Table 2

Diarrhea (7 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	0 / 194	not stated; safety; registry:adverse_events
A1	events	14 / 194	treatment policy; safety; R0017387:Table 2
A2	events	0 / 190	not stated; safety; registry:adverse_events
A2	events	30 / 190	treatment policy; safety; R0017387:Table 2
A3	events	2 / 192	not stated; safety; registry:adverse_events
A3	events	31 / 192	not stated; safety; registry:adverse_events
A3	events	33 / 192	treatment policy; safety; R0017387:Table 2

Constipation (3 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	6 / 194	treatment policy; safety; R0017387:Table 2
A2	events	10 / 190	treatment policy; safety; R0017387:Table 2
A3	events	12 / 192	treatment policy; safety; R0017387:Table 2

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 194	treatment policy; safety; R0017387:Results
A2	events	4 / 190	treatment policy; safety; R0017387:Results
A3	events	13 / 192	treatment policy; safety; R0017387:Results

Gallbladder and biliary disease (3 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 194	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	2 / 190	not stated; safety; cholecystitis acute; registry:adverse_events
A3	events	0 / 192	not stated; safety; cholecystitis acute; registry:adverse_events

Acute pancreatitis (6 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 194	not stated; safety; registry:adverse_events
A1	events	1 / 194	treatment policy; safety; pancreatitis; R0017387:Table 2
A2	events	0 / 190	treatment policy; safety; pancreatitis; R0017387:Table 2
A2	events	0 / 190	not stated; safety; registry:adverse_events
A3	events	2 / 192	treatment policy; safety; pancreatitis; R0017387:Table 2
A3	events	2 / 192	not stated; safety; registry:adverse_events

Medullary thyroid carcinoma (3 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 194	treatment policy; safety; R0017387:Supplement Results
A2	events	0 / 190	treatment policy; safety; R0017387:Supplement Results
A3	events	0 / 192	treatment policy; safety; R0017387:Supplement Results

Thyroid cancer (any) (3 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 194	treatment policy; safety; R0017387:Supplement Results
A2	events	0 / 190	treatment policy; safety; R0017387:Supplement Results
A3	events	0 / 192	treatment policy; safety; R0017387:Supplement Results

eGFR total slope (15 lines; O51)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	change	-2.9 mL/min/1.73 m2	-4.2 to -1.6	164	not stated; safety; R0017387:Supplement Table 8
52	A1	change	mL/min/1.73 m2		164	not stated; safety; registry:outcomes
52	A1	change	-2.1 mL/min/1.73 m2	-4.2 to -0.0	95	not stated; safety; uacr:300_or_less; R0017387:Supplement Table 9
52	A1	change	-5.5 mL/min/1.73 m2	-8.5 to -2.5	69	not stated; safety; uacr:more_than_300; R0017387:Supplement Table 9
52	A1	change	-3.3 mL/min/1.73 m2	-5.1 to -1.6	164	not stated; safety; R0017387:Supplement Table 8
52	A2	change	mL/min/1.73 m2		160	not stated; safety; registry:outcomes
52	A2	change	-0.7 mL/min/1.73 m2	-3.8 to 2.4	67	not stated; safety; uacr:more_than_300; R0017387:Supplement Table 9
52	A2	change	-1.5 mL/min/1.73 m2	-2.8 to -0.2	160	not stated; safety; R0017387:Supplement Table 8
52	A2	change	-1.4 mL/min/1.73 m2	-3.5 to 0.7	93	not stated; safety; uacr:300_or_less; R0017387:Supplement Table 9
52	A2	change	-0.7 mL/min/1.73 m2	-2.4 to 1.1	160	not stated; safety; R0017387:Supplement Table 8
52	A3	change	-0.5 mL/min/1.73 m2	-3.6 to 2.7	64	not stated; safety; uacr:more_than_300; R0017387:Supplement Table 9
52	A3	change	-1.1 mL/min/1.73 m2	-2.4 to 0.2	157	not stated; safety; R0017387:Supplement Table 8
52	A3	change	mL/min/1.73 m2		157	not stated; safety; registry:outcomes
52	A3	change	-0.7 mL/min/1.73 m2	-2.5 to 1.0	157	not stated; safety; R0017387:Supplement Table 8
52	A3	change	-1.6 mL/min/1.73 m2	-3.7 to -0.5	93	not stated; safety; uacr:300_or_less; R0017387:Supplement Table 9