parallel randomized trial

NCT01191268

The Impact of LY2189265 Versus Insulin Glargine in Combination With Insulin Lispro for the Treatment to Target of Type 2 Diabetes Mellitus (AWARD-4: Assessment of Weekly AdministRation of LY2189265 in Diabetes - 4)

Type 2 diabetes (adults)NCT01191268S001198

Design

Randomized: 884
Start year: 2010
Treatment: 52 weeks, follow-up 56 weeks
Countries: Argentina, Australia, Belgium, Brazil, Canada, Denmark, Greece, Hungary, Mexico, Poland, Puerto Rico, Russian Federation, Spain, Sweden, Taiwan, United States
Sponsor: Eli Lilly and Company (industry)
Eligibility: adults with type 2 diabetes on conventional insulin with or without metformin

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 plus lispro	insulin lispro TID titrated, with or without metformin; lifestyle: not reported	295	295
A2	Dulaglutide 0.75 mg subcutaneous once weekly Dulaglutide 0.75 mg plus lispro	insulin lispro TID titrated, with or without metformin; lifestyle: not reported	293	293
A3	Insulin glargine Insulin glargine plus lispro	insulin lispro TID titrated, with or without metformin; lifestyle: not reported	296	296

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: >=65	n			90
age	mean (years)	58.88	59.31	59.9
age	sd (years)	9.55	8.98	9.08
asian	n	9	12	14
black	n	32	27	26
bmi	mean (kg/m2)	31.99	33.08	32.41
bmi	sd (kg/m2)	5.11	5.15	5.33
diabetes duration: >=10	n			199
diabetes duration	mean (years)	12.80	12.43	12.96
diabetes duration	sd (years)	7.19	6.92	6.80
egfr: <60	n				93
egfr: <60	percent				10.5
female	n	135	145	131
hba1c: >9	n			92
hba1c	mean (percent)	8.46	8.40	8.53
hba1c	sd (percent)	1.08	1.03	1.03
hispanic	n	102	101	100
insulin dose	mean (U/day)	55.20	59.11	53.93
other race american indian alaska native	n	16	13	17
other race multiple	n	7	6	7
other race native hawaiian pacific islander	n	0	0	1
sbp	mean (mmHg)	133.26	134.03	133.26
sbp	sd (mmHg)	16.56	15.87	16.97
uacr: >300	n				52
uacr: >300	percent				5.9
weight	mean (kg)	91.00	91.69	90.75
weight	sd (kg)	18.24	18.03	18.87
white	n	231	235	231

Analyses this trial contributes to

Results

110 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 vs A3	md	-0.22 percent		-0.38 to -0.07		hypothetical; modified itt; registry:outcomes
26	A1	change	-1.64 percent	0.07		273	hypothetical; modified itt; registry:outcomes
26	A2	change	-1.59 percent	0.07		275	hypothetical; modified itt; registry:outcomes
26	A2 vs A3	md	-0.17 percent		-0.33 to -0.02		hypothetical; modified itt; registry:outcomes
26	A3	change	-1.41 percent	0.07		276	hypothetical; modified itt; registry:outcomes
52	A1	change	-1.48 percent	0.08		273	hypothetical; modified itt; registry:outcomes
52	A1 vs A3	md	-0.25 percent		-0.42 to -0.07		hypothetical; modified itt; registry:outcomes
52	A2	change	-1.42 percent	0.08		275	hypothetical; modified itt; registry:outcomes
52	A2 vs A3	md	-0.19 percent		-0.37 to -0.02		hypothetical; modified itt; registry:outcomes
52	A3	change	-1.23 percent	0.08		276	hypothetical; modified itt; registry:outcomes

Body weight change in kilograms (diabetes) (31 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A3	md	-3.20 kg		-3.81 to -2.59		not stated; modified itt; registry:outcomes
26	A1	change	-0.87 kg	0.27		286	not stated; modified itt; registry:outcomes
26	A2	change	0.18 kg	0.27		289	not stated; modified itt; registry:outcomes
26	A2 vs A3	md	-2.15 kg		-2.76 to -1.54		not stated; modified itt; registry:outcomes
26	A3	change	2.33 kg	0.27		294	not stated; modified itt; registry:outcomes
26.07	A1	change	-0.33 kg		-0.98 to 0.33		not stated; modified itt; sex:male; R0014882:Table 2
26.07	A1	change	-1.63 kg		-2.37 to -0.88		not stated; modified itt; sex:female; R0014882:Table 2
26.07	A1	change	0.31 kg		-0.57 to 1.19		not stated; modified itt; diabetes_duration:>=5_<10; R0014882:Table 2
26.07	A1	change	0.06 kg		-0.64 to 0.76		not stated; modified itt; hba1c:>=8.5; R0014882:Table 2
26.07	A1	change	-1.71 kg		-2.39 to -1.04		not stated; modified itt; hba1c:<8.5; R0014882:Table 2
26.07	A1	change	-1.64 kg		-3.04 to -0.24		not stated; modified itt; diabetes_duration:<5; R0014882:Table 2
26.07	A1	change	-0.96 kg		-1.55 to -0.38		not stated; modified itt; diabetes_duration:>=10; R0014882:Table 2
26.07	A2	change	0.95 kg		0.24 to 1.67		not stated; modified itt; hba1c:>=8.5; R0014882:Table 2
26.07	A2	change	0.21 kg		-1.09 to 1.51		not stated; modified itt; diabetes_duration:<5; R0014882:Table 2
26.07	A2	change	0.54 kg		-0.04 to 1.13		not stated; modified itt; diabetes_duration:>=10; R0014882:Table 2
26.07	A2	change	0.08 kg		-0.84 to 1.00		not stated; modified itt; diabetes_duration:>=5_<10; R0014882:Table 2
26.07	A2	change	-0.46 kg		-1.10 to 0.19		not stated; modified itt; hba1c:<8.5; R0014882:Table 2
26.07	A2	change	-0.33 kg		-1.04 to 0.37		not stated; modified itt; sex:female; R0014882:Table 2
26.07	A2	change	0.61 kg		-0.07 to 1.28		not stated; modified itt; sex:male; R0014882:Table 2
26.07	A3	change	2.66 kg		2.09 to 3.23		not stated; modified itt; diabetes_duration:>=10; R0014882:Table 2
26.07	A3	change	2.19 kg		1.25 to 3.12		not stated; modified itt; diabetes_duration:>=5_<10; R0014882:Table 2
26.07	A3	change	1.70 kg		1.03 to 2.38		not stated; modified itt; hba1c:<8.5; R0014882:Table 2
26.07	A3	change	2.96 kg		2.28 to 3.63		not stated; modified itt; hba1c:>=8.5; R0014882:Table 2
26.07	A3	change	1.98 kg		0.58 to 3.38		not stated; modified itt; diabetes_duration:<5; R0014882:Table 2
26.07	A3	change	2.20 kg		1.47 to 2.93		not stated; modified itt; sex:female; R0014882:Table 2
26.07	A3	change	2.34 kg		1.69 to 3.00		not stated; modified itt; sex:male; R0014882:Table 2
52	A1	change	-0.35 kg	0.34		286	not stated; modified itt; registry:outcomes
52	A1 vs A3	md	-3.23 kg		-3.99 to -2.48		not stated; modified itt; registry:outcomes
52	A2 vs A3	md	-2.03 kg		-2.78 to -1.27		not stated; modified itt; registry:outcomes
52	A2	change	0.86 kg	0.33		289	not stated; modified itt; registry:outcomes
52	A3	change	2.89 kg	0.33		294	not stated; modified itt; registry:outcomes

HbA1c below 7 percent (6 lines; O03)

Week	Arm	Statistic	Estimate	Events / N	Detail
26	A1	responders	67.6	275	hypothetical; modified itt; registry:outcomes
26	A2	responders	69.0	277	hypothetical; modified itt; registry:outcomes
26	A3	responders	56.8	280	hypothetical; modified itt; registry:outcomes
52	A1	responders	58.5	275	hypothetical; modified itt; registry:outcomes
52	A2	responders	56.3	277	hypothetical; modified itt; registry:outcomes
52	A3	responders	49.3	280	hypothetical; modified itt; registry:outcomes

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

Arm	Statistic	Events / N	Detail
A1	events	4 / 295	hypothetical; safety; registry:outcomes
A1	events	8 / 295	hypothetical; safety; registry:outcomes
A2	events	5 / 293	hypothetical; safety; registry:outcomes
A2	events	7 / 293	hypothetical; safety; registry:outcomes
A3	events	14 / 296	hypothetical; safety; registry:outcomes
A3	events	9 / 296	hypothetical; safety; registry:outcomes

Systolic blood pressure change (6 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
26	A1	change	-0.97 mmHg	0.88	255	not stated; modified itt; registry:outcomes
26	A2	change	-0.65 mmHg	0.87	261	not stated; modified itt; registry:outcomes
26	A3	change	2.23 mmHg	0.88	258	not stated; modified itt; registry:outcomes
52	A1	change	-0.26 mmHg	0.94	239	not stated; modified itt; registry:outcomes
52	A2	change	1.04 mmHg	0.93	240	not stated; modified itt; registry:outcomes
52	A3	change	1.98 mmHg	0.92	246	not stated; modified itt; registry:outcomes

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 295	not stated; randomized; registry:flow
A2	events	1 / 293	not stated; randomized; registry:flow
A3	events	3 / 296	not stated; randomized; registry:flow

Physical functioning (any instrument) (6 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
26	A1	change	-0.50 points	0.30	274	hypothetical; modified itt; registry:outcomes
26	A2	change	-0.60 points	0.31	270	hypothetical; modified itt; registry:outcomes
26	A3	change	-0.93 points	0.31	270	hypothetical; modified itt; registry:outcomes
52	A1	change	-0.50 points	0.33	277	hypothetical; modified itt; registry:outcomes
52	A2	change	-1.05 points	0.33	275	hypothetical; modified itt; registry:outcomes
52	A3	change	-1.28 points	0.33	279	hypothetical; modified itt; registry:outcomes

Health related quality of life total score (any instrument) (6 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
26	A1	change	-0.03 points	0.01	272	hypothetical; modified itt; registry:outcomes
26	A2	change	-0.03 points	0.01	271	hypothetical; modified itt; registry:outcomes
26	A3	change	-0.03 points	0.01	274	hypothetical; modified itt; registry:outcomes
52	A1	change	-0.04 points	0.01	274	hypothetical; modified itt; registry:outcomes
52	A2	change	-0.04 points	0.01	274	hypothetical; modified itt; registry:outcomes
52	A3	change	-0.03 points	0.01	281	hypothetical; modified itt; registry:outcomes

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	27 / 295	not stated; safety; registry:adverse_events
A2	events	46 / 293	not stated; safety; registry:adverse_events
A3	events	53 / 296	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	21 / 295	not stated; randomized; registry:flow
A2	events	13 / 293	not stated; randomized; registry:flow
A3	events	8 / 296	not stated; randomized; registry:flow

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	76 / 295	not stated; safety; registry:adverse_events
A2	events	52 / 293	not stated; safety; registry:adverse_events
A3	events	9 / 296	not stated; safety; registry:adverse_events

Vomiting (3 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	35 / 295	not stated; safety; registry:adverse_events
A2	events	31 / 293	not stated; safety; registry:adverse_events
A3	events	5 / 296	not stated; safety; registry:adverse_events

Diarrhea (9 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	44 / 295	not stated; safety; registry:adverse_events
A1	events	0 / 295	not stated; safety; registry:adverse_events
A1	events	0 / 295	not stated; safety; Chronic diarrhea; registry:adverse_events
A2	events	34 / 293	not stated; safety; registry:adverse_events
A2	events	1 / 293	not stated; safety; registry:adverse_events
A2	events	1 / 293	not stated; safety; Chronic diarrhea; registry:adverse_events
A3	events	15 / 296	not stated; safety; registry:adverse_events
A3	events	0 / 296	not stated; safety; registry:adverse_events
A3	events	0 / 296	not stated; safety; Chronic diarrhea; registry:adverse_events

Constipation (3 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	12 / 295	not stated; safety; registry:adverse_events
A2	events	6 / 293	not stated; safety; registry:adverse_events
A3	events	5 / 296	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (6 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 295	not stated; safety; Cholecystitis acute; registry:adverse_events
A1	events	0 / 295	not stated; safety; Cholelithiasis; registry:adverse_events
A2	events	0 / 293	not stated; safety; Cholecystitis acute; registry:adverse_events
A2	events	2 / 293	not stated; safety; Cholelithiasis; registry:adverse_events
A3	events	1 / 296	not stated; safety; Cholecystitis acute; registry:adverse_events
A3	events	0 / 296	not stated; safety; Cholelithiasis; registry:adverse_events

Acute pancreatitis (3 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 295	not stated; safety; registry:outcomes
A2	events	0 / 293	not stated; safety; registry:outcomes
A3	events	0 / 296	not stated; safety; registry:outcomes

Intestinal obstruction or ileus (3 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 295	not stated; safety; Ileus paralytic; registry:adverse_events
A2	events	0 / 293	not stated; safety; Ileus paralytic; registry:adverse_events
A3	events	0 / 296	not stated; safety; Ileus paralytic; registry:adverse_events