parallel randomized trial

AWARD-2

A Randomized, Open-Label, Parallel-Arm, Noninferiority Comparison of the Effects of Two Doses of LY2189265 and Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes on Stable Doses of Metformin and Glimepiride

Type 2 diabetes (adults)NCT01075282S001130

Design

Randomized: 810
Start year: 2010
Treatment: 78 weeks, follow-up 83 weeks
Countries: multinational
Sponsor: Eli Lilly and Company (industry)
Eligibility: type 2 diabetes on metformin and glimepiride

Conduct and analysis

Blinding: open label
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: yes
Primary estimand: hypothetical
Analysis population: modified itt
Missing data: LOCF

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Dulaglutide 1.5 mg subcutaneous once weekly Dulaglutide 1.5 mg	metformin at least 1500 mg/day and glimepiride at least 4 mg/day; lifestyle: not reported	273	263
A2	Dulaglutide 0.75 mg subcutaneous once weekly Dulaglutide 0.75 mg	metformin at least 1500 mg/day and glimepiride at least 4 mg/day; lifestyle: not reported	272	267
A3	Insulin glargine Insulin glargine	metformin at least 1500 mg/day and glimepiride at least 4 mg/day; lifestyle: not reported	265	259

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	Dulaglutide 0.75 mg subcutaneous once weekly A2	Insulin glargine A3	Whole trial ALL
age	mean (years)	56.24	56.56	57.21
age	sd (years)	9.76	9.27	9.38
asian	n	48	46	43
black	n	1	1	2
bmi	mean (kg/m2)	31.23	31.51	31.91
bmi	sd (kg/m2)	5.21	5.41	5.76
diabetes duration	mean (years)	9.13	9.28	8.87
diabetes duration	sd (years)	6.22	5.93	5.98
egfr: less than 60	n				9
egfr: less than 60	percent				1.1
female	n	129	136	128
hba1c	mean (percent)	8.18	8.13	8.10
hba1c	sd (percent)	1.03	0.98	0.95
hispanic	n	98	96	97
other race american indian alaska native	n	29	31	29
other race multiple	n	2	1	4
other race native hawaiian pacific islander	n	0	0	0
weight	mean (kg)	85.13	86.18	87.66
weight	sd (kg)	17.90	18.15	19.62
white	n	193	193	184

Analyses this trial contributes to

Results

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

HbA1c change (15 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.16 percent	0.06		263	hypothetical; modified itt; registry:outcomes
26	A1 vs A3	md	-0.51 percent		-0.65 to -0.37		hypothetical; modified itt; registry:outcomes
26	A2	change	-0.89 percent	0.05		266	hypothetical; modified itt; registry:outcomes
26	A2 vs A3	md	-0.24 percent		-0.38 to -0.10		hypothetical; modified itt; registry:outcomes
26	A3	change	-0.65 percent	0.06		258	hypothetical; modified itt; registry:outcomes
52	A1	change	-1.08 percent	0.06		263	hypothetical; modified itt; registry:outcomes
52	A1 vs A3	md	-0.45 percent		-0.60 to -0.29		hypothetical; modified itt; registry:outcomes
52	A2	change	-0.76 percent	0.06		267	hypothetical; modified itt; registry:outcomes
52	A2 vs A3	md	-0.13 percent		-0.29 to 0.02		hypothetical; modified itt; registry:outcomes
52	A3	change	-0.63 percent	0.06		259	hypothetical; modified itt; registry:outcomes
78	A1	change	-0.90 percent	0.07		263	hypothetical; modified itt; registry:outcomes
78	A1 vs A3	md	-0.31 percent		-0.50 to -0.13		hypothetical; modified itt; registry:outcomes
78	A2	change	-0.62 percent	0.07		267	hypothetical; modified itt; registry:outcomes
78	A2 vs A3	md	-0.03 percent		-0.21 to 0.15		hypothetical; modified itt; registry:outcomes
78	A3	change	-0.59 percent	0.07		259	hypothetical; modified itt; registry:outcomes

Body weight change in kilograms (diabetes) (15 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-1.82 kg	0.20		272	hypothetical; modified itt; registry:outcomes
26	A2	change	-1.47 kg	0.20		270	hypothetical; modified itt; registry:outcomes
26	A3	change	1.01 kg	0.20		259	hypothetical; modified itt; registry:outcomes
26	A3 vs A1	md	2.83 kg		2.33 to 3.33		hypothetical; modified itt; registry:outcomes
26	A3 vs A2	md	2.48 kg		1.99 to 2.99		hypothetical; modified itt; registry:outcomes
52	A1	change	-1.87 kg	0.24		272	hypothetical; modified itt; registry:outcomes
52	A2	change	-1.33 kg	0.24		270	hypothetical; modified itt; registry:outcomes
52	A3	change	1.44 kg	0.24		259	hypothetical; modified itt; registry:outcomes
52	A3 vs A1	md	3.31 kg		2.71 to 3.90		hypothetical; modified itt; registry:outcomes
52	A3 vs A2	md	2.77 kg		2.17 to 3.36		hypothetical; modified itt; registry:outcomes
78	A1	change	-1.96 kg	0.26		272	hypothetical; modified itt; registry:outcomes
78	A2	change	-1.54 kg	0.26		270	hypothetical; modified itt; registry:outcomes
78	A3	change	1.28 kg	0.26		259	hypothetical; modified itt; registry:outcomes
78	A3 vs A1	md	3.24 kg		2.59 to 3.89		hypothetical; modified itt; registry:outcomes
78	A3 vs A2	md	2.82 kg		2.17 to 3.46		hypothetical; modified itt; registry:outcomes

HbA1c below 7 percent (15 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
26	A1	responders			153 / 263	hypothetical; modified itt; registry:outcomes
26	A1 vs A3	or	4.61	2.98 to 7.11		hypothetical; modified itt; registry:outcomes
26	A2	responders			122 / 266	hypothetical; modified itt; registry:outcomes
26	A2 vs A3	or	2.13	1.41 to 3.24		hypothetical; modified itt; registry:outcomes
26	A3	responders			84 / 258	hypothetical; modified itt; registry:outcomes
52	A1	responders			140 / 263	hypothetical; modified itt; registry:outcomes
52	A1 vs A3	or	3.76	2.45 to 5.75		hypothetical; modified itt; registry:outcomes
52	A2	responders			99 / 267	hypothetical; modified itt; registry:outcomes
52	A2 vs A3	or	1.42	0.94 to 2.15		hypothetical; modified itt; registry:outcomes
52	A3	responders			80 / 259	hypothetical; modified itt; registry:outcomes
78	A1	responders			129 / 263	hypothetical; modified itt; registry:outcomes
78	A1 vs A3	or	2.77	1.85 to 4.14		hypothetical; modified itt; registry:outcomes
78	A2	responders			91 / 267	hypothetical; modified itt; registry:outcomes
78	A2 vs A3	or	1.22	0.82 to 1.82		hypothetical; modified itt; registry:outcomes
78	A3	responders			79 / 259	hypothetical; modified itt; registry:outcomes

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

Arm	Statistic	Estimate	Events / N	Detail
A1	events	13.6	273	not stated; modified itt; R0022281:Table 3
A2	events	12.5	272	not stated; modified itt; R0022281:Table 3
A3	events	16.8	262	not stated; modified itt; R0022281:Table 3

Systolic blood pressure change (9 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
26	A1	change	-1.28 mmHg	0.78	257	not stated; modified itt; registry:outcomes
26	A2	change	-1.6 mmHg	0.78	261	not stated; modified itt; registry:outcomes
26	A3	change	-0.03 mmHg	0.8	245	not stated; modified itt; registry:outcomes
52	A1	change	0.17 mmHg	0.81	250	not stated; modified itt; registry:outcomes
52	A2	change	0.09 mmHg	0.8	252	not stated; modified itt; registry:outcomes
52	A3	change	0.51 mmHg	0.83	240	not stated; modified itt; registry:outcomes
78	A1	change	-0.7 mmHg	0.85	246	not stated; modified itt; registry:outcomes
78	A2	change	-0.59 mmHg	0.85	244	not stated; modified itt; registry:outcomes
78	A3	change	0.51 mmHg	0.87	238	not stated; modified itt; registry:outcomes

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 273	not stated; randomized; registry:flow
A2	events	1 / 272	not stated; randomized; registry:flow
A3	events	2 / 265	not stated; randomized; registry:flow

Physical functioning (any instrument) (9 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
26	A1	change	0.7 points	0.30	256	hypothetical; modified itt; registry:outcomes
26	A2	change	0.1 points	0.30	256	hypothetical; modified itt; registry:outcomes
26	A3	change	-0.3 points	0.30	248	hypothetical; modified itt; registry:outcomes
52	A1	change	0.9 points	0.31	260	hypothetical; modified itt; registry:outcomes
52	A2	change	0.4 points	0.31	261	hypothetical; modified itt; registry:outcomes
52	A3	change	-0.6 points	0.32	249	hypothetical; modified itt; registry:outcomes
78	A1	change	1.0 points	0.31	260	hypothetical; modified itt; registry:outcomes
78	A2	change	0.3 points	0.31	261	hypothetical; modified itt; registry:outcomes
78	A3	change	-0.3 points	0.32	249	hypothetical; modified itt; registry:outcomes

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

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
26	A1	change	0.01 points	0.01	257	hypothetical; modified itt; registry:outcomes
26	A2	change	0.00 points	0.01	254	hypothetical; modified itt; registry:outcomes
26	A3	change	-0.01 points	0.01	249	hypothetical; modified itt; registry:outcomes
52	A1	change	0.01 points	0.01	259	hypothetical; modified itt; registry:outcomes
52	A2	change	0.00 points	0.01	260	hypothetical; modified itt; registry:outcomes
52	A3	change	-0.04 points	0.01	253	hypothetical; modified itt; registry:outcomes
78	A1	change	0.01 points	0.01	259	hypothetical; modified itt; registry:outcomes
78	A2	change	0.00 points	0.01	260	hypothetical; modified itt; registry:outcomes
78	A3	change	0.00 points	0.01	253	hypothetical; modified itt; registry:outcomes

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	32 / 273	not stated; safety; registry:adverse_events
A2	events	28 / 272	not stated; safety; registry:adverse_events
A3	events	33 / 262	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	9 / 273	not stated; randomized; registry:flow
A2	events	8 / 272	not stated; randomized; registry:flow
A3	events	5 / 265	not stated; randomized; registry:flow

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	42 / 273	not stated; safety; registry:adverse_events
A2	events	22 / 272	not stated; safety; registry:adverse_events
A3	events	4 / 262	not stated; safety; registry:adverse_events

Vomiting (3 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	18 / 273	not stated; safety; registry:adverse_events
A2	events	10 / 272	not stated; safety; registry:adverse_events
A3	events	3 / 262	not stated; safety; registry:adverse_events

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	29 / 273	not stated; safety; registry:adverse_events
A2	events	26 / 272	not stated; safety; registry:adverse_events
A3	events	15 / 262	not stated; safety; registry:adverse_events

Constipation (3 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	12 / 273	not stated; safety; registry:adverse_events
A2	events	3 / 272	not stated; safety; registry:adverse_events
A3	events	3 / 262	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (3 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 273	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	1 / 272	not stated; safety; cholelithiasis; registry:adverse_events
A3	events	2 / 262	not stated; safety; cholelithiasis; registry:adverse_events

Acute pancreatitis (6 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	2 / 273	not stated; safety; registry:outcomes
A1	events	1 / 273	not stated; safety; registry:adverse_events
A2	events	1 / 272	not stated; safety; registry:outcomes
A2	events	0 / 272	not stated; safety; registry:adverse_events
A3	events	0 / 262	not stated; safety; registry:outcomes
A3	events	0 / 262	not stated; safety; registry:adverse_events

Thyroid cancer (any) (3 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 273	not stated; safety; registry:adverse_events
A2	events	0 / 272	not stated; safety; registry:adverse_events
A3	events	0 / 262	not stated; safety; registry:adverse_events