parallel randomized trial

NCT01558271

A Phase 3 Study of LY2189265 Monotherapy Compared to Placebo and Liraglutide in Patients With Type 2 Diabetes Mellitus

Type 2 diabetes (adults)NCT01558271S000837

Design

Randomized: 492
Start year: 2012
Treatment: 52 weeks, follow-up 56.29 weeks
Countries: Japan (33 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: Japanese; age 20 or more; BMI 18.5 to 35; HbA1c 7.0 to 10.0 percent; OAM naive or OAM stopped

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: hypothetical
Analysis population: full analysis
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Dulaglutide 0.75 mg subcutaneous once weekly Dulaglutide 0.75 mg	none, monotherapy; lifestyle: not reported	281	280
A2	Liraglutide 0.9 mg injection once daily Liraglutide 0.9 mg	none, monotherapy; lifestyle: not reported	141	137
A3	Placebo Placebo	none, monotherapy; lifestyle: not reported	70	70

Baseline characteristics

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

Characteristic	Statistic	Dulaglutide 0.75 mg subcutaneous once weekly A1	Liraglutide 0.9 mg injection once daily A2	Placebo A3
age: 65 or older	n	68	39	13
age: 65 or older	percent	24	29	19
age	mean (years)	57.2	57.9	57.7
age	sd (years)	9.6	10.4	8.3
asian	n	280	137	70
bmi	mean (kg/m2)	25.6	25.5	25.2
bmi	sd (kg/m2)	3.6	3.5	3.2
diabetes duration	mean (years)	6.8	6.3	6.3
diabetes duration	sd (years)	5.6	6.0	5.1
egfr	median (mL/min/1.73 m2)	73.23	70.26	73.00
female	n	52	24	15
female	percent	19	18	21
hba1c: more than 8.5	n	89	42	26
hba1c: more than 8.5	percent	32	31	37
hba1c	mean (percent)	8.15	8.08	8.20
hba1c	sd (percent)	0.77	0.89	0.83
uacr	median (mg/g)	12.39	13.28	10.62
weight	mean (kg)	71.3	70.2	69.3
weight	sd (kg)	12.5	12.5	11.6

Analyses this trial contributes to

Results

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

HbA1c change (18 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1 vs A3	md	-1.57 percent		-1.79 to -1.35		not stated; full analysis; R0011901:Results
26	A1 vs A2	md	-0.10 percent		-0.27 to 0.07		not stated; full analysis; R0011901:Results
26	A1	change	-1.43 percent	0.05		280	not stated; full analysis; R0011901:Results
26	A2	change	-1.33 percent	0.07		136	not stated; full analysis; R0011901:Results
26	A3	change	0.14 percent	0.10		68	not stated; full analysis; R0011901:Results
52	A1 vs A2	md	-0.20 percent		-0.39 to -0.01		not stated; full analysis; R0011754:Results
52	A1	change	-1.45 percent	0.07		186	not stated; full analysis; background:no_prior_oam; R0011754:Results
52	A1	final	6.74 percent				not stated; full analysis; R0011754:Figure 2
52	A1	change	-1.49 percent			52	not stated; modified itt; sex:female; R0022460:Table 3
52	A1	change	-1.37 percent			228	not stated; modified itt; sex:male; R0022460:Table 3
52	A1	change	-1.39 percent	0.06		280	not stated; full analysis; R0011754:Results
52	A1	change	-1.35 percent	0.09		94	not stated; full analysis; background:prior_oam; R0011754:Results
52	A2	change	-1.26 percent	0.13		47	not stated; full analysis; background:prior_oam; R0011754:Results
52	A2	change	-1.19 percent	0.08		136	not stated; full analysis; R0011754:Results
52	A2	final	6.94 percent				not stated; full analysis; R0011754:Figure 2
52	A2	change	-1.21 percent	0.10		88	not stated; full analysis; background:no_prior_oam; R0011754:Results
52	A2	change	-1.36 percent			24	not stated; modified itt; sex:female; R0022460:Table 3
52	A2	change	-1.17 percent			113	not stated; modified itt; sex:male; R0022460:Table 3

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26	A1	change	-0.02 kg	0.14		280	hypothetical; modified itt; registry:outcomes
26	A1 vs A3	md	0.61 kg		-0.02 to 1.23		hypothetical; modified itt; registry:outcomes
26	A1 vs A2	md	0.34 kg		-0.14 to 0.82		hypothetical; modified itt; registry:outcomes
26	A1	change	-0.02 kg				not stated; full analysis; R0011901:Results
26	A2	change	-0.36 kg				not stated; full analysis; R0011901:Results
26	A2	change	-0.36 kg	0.20		136	hypothetical; modified itt; registry:outcomes
26	A3	change	-0.63 kg				not stated; full analysis; R0011901:Results
26	A3	change	-0.63 kg	0.29		70	hypothetical; modified itt; registry:outcomes
52	A1	change	0.09 kg			228	not stated; modified itt; sex:male; R0022460:Table 3
52	A1	change	-0.17 kg	0.18		280	hypothetical; modified itt; registry:outcomes
52	A1 vs A2	md	-0.03 kg		-0.64 to 0.57		hypothetical; modified itt; registry:outcomes
52	A1	change	-0.17 kg				not stated; full analysis; R0011754:Results
52	A1	change	-1.32 kg			52	not stated; modified itt; sex:female; R0022460:Table 3
52	A2	change	-0.13 kg	0.26		136	hypothetical; modified itt; registry:outcomes
52	A2	change	-0.13 kg				not stated; full analysis; R0011754:Results
52	A2	change	-0.03 kg			113	not stated; modified itt; sex:male; R0022460:Table 3
52	A2	change	-0.51 kg			24	not stated; modified itt; sex:female; R0022460:Table 3

HbA1c below 7 percent (5 lines; O03)

Week	Arm	Statistic	Events / N	Detail
26	A1	responders	200 / 280	not stated; full analysis; R0011901:Results
26	A2	responders	94 / 136	not stated; full analysis; R0011901:Results
26	A3	responders	4 / 68	not stated; full analysis; R0011901:Results
52	A1	responders	190 / 280	not stated; full analysis; R0011754:Results
52	A2	responders	82 / 136	not stated; full analysis; R0011754:Results

Level 2 or 3 hypoglycemia (participants) (10 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 280	not stated; safety; R0011901:Results
A1	events	8 / 280	not stated; safety; R0011754:Results
A1	events	6 / 280	not stated; safety; R0011901:Results
A1	events	0 / 280	not stated; safety; R0011754:Results
A2	events	4 / 137	not stated; safety; R0011754:Results
A2	events	0 / 137	not stated; safety; R0011901:Results
A2	events	0 / 137	not stated; safety; R0011754:Results
A2	events	2 / 137	not stated; safety; R0011901:Results
A3	events	1 / 70	not stated; safety; R0011901:Results
A3	events	0 / 70	not stated; safety; R0011901:Results

Level 2 or 3 hypoglycemia (episode rate) (5 lines; O04B)

Arm	Statistic	Estimate	Detail
A1	rate	0.01	not stated; safety; registry:outcomes
A1	rate	0.00	not stated; safety; registry:outcomes
A2	rate	0.01	not stated; safety; registry:outcomes
A2	rate	0.00	not stated; safety; registry:outcomes
A3	rate	0.00	not stated; safety; registry:outcomes

Systolic blood pressure change (7 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
26	A1	change	0.62 mmHg	0.62	280	not stated; safety; R0011901:Table 2
26	A2	change	-2.10 mmHg	0.89	136	not stated; safety; R0011901:Table 2
26	A3	change	0.53 mmHg	1.25	70	not stated; safety; R0011901:Table 2
52	A1	change	1.32 mmHg	0.66	280	hypothetical; modified itt; registry:outcomes
52	A1	change	1.45 mmHg	0.64		not stated; safety; R0011754:Table 2
52	A2	change	-1.86 mmHg	0.95	136	hypothetical; modified itt; registry:outcomes
52	A2	change	-1.58 mmHg	0.92		not stated; safety; R0011754:Table 2

All cause mortality (5 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 280	while on treatment; safety; R0011754:Table 2
A1	events	0 / 280	not stated; safety; R0011901:Table 2
A2	events	0 / 137	not stated; safety; R0011901:Table 2
A2	events	0 / 137	while on treatment; safety; R0011754:Table 2
A3	events	0 / 70	not stated; safety; R0011901:Table 2

Three point MACE (5 lines; O21)

Arm	Statistic	Events / N	Detail
A1	events	0 / 280	not stated; safety; registry:outcomes
A1	events	0 / 280	not stated; safety; registry:outcomes
A2	events	0 / 137	not stated; safety; registry:outcomes
A2	events	0 / 137	not stated; safety; registry:outcomes
A3	events	0 / 70	not stated; safety; registry:outcomes

Four point MACE including unstable angina (5 lines; O21B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 280	not stated; safety; registry:outcomes
A1	events	0 / 280	not stated; safety; registry:outcomes
A2	events	0 / 137	not stated; safety; registry:outcomes
A2	events	0 / 137	not stated; safety; registry:outcomes
A3	events	0 / 70	not stated; safety; registry:outcomes

Hospitalization for heart failure (5 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 280	not stated; safety; registry:outcomes
A1	events	0 / 280	not stated; safety; registry:outcomes
A2	events	0 / 137	not stated; safety; registry:outcomes
A2	events	0 / 137	not stated; safety; registry:outcomes
A3	events	0 / 70	not stated; safety; registry:outcomes

Serious adverse events (5 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	3 / 280	not stated; safety; R0011901:Table 2
A1	events	9 / 280	while on treatment; safety; R0011754:Table 2
A2	events	2 / 137	not stated; safety; R0011901:Table 2
A2	events	7 / 137	while on treatment; safety; R0011754:Table 2
A3	events	2 / 70	not stated; safety; R0011901:Table 2

Discontinuation due to adverse events (7 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	3 / 280	not stated; safety; R0011901:Table 2
A1	events	5 / 280	while on treatment; safety; R0011754:Table 2
A1	events	6 / 281	not stated; randomized; registry:flow
A2	events	4 / 137	while on treatment; safety; R0011754:Table 2
A2	events	1 / 137	not stated; safety; R0011901:Table 2
A2	events	4 / 141	not stated; randomized; registry:flow
A3	events	0 / 70	not stated; safety; R0011901:Table 2

Nausea (5 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	17 / 280	while on treatment; safety; R0011754:Table 2
A1	events	15 / 280	not stated; safety; R0011901:Table 2
A2	events	11 / 137	not stated; safety; R0011901:Table 2
A2	events	11 / 137	while on treatment; safety; R0011754:Table 2
A3	events	1 / 70	not stated; safety; R0011901:Table 2

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				5 / 280	not stated; safety; registry:adverse_events
	A2	events				1 / 137	not stated; safety; registry:adverse_events

Diarrhea (5 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	16 / 280	not stated; safety; R0011901:Table 2
A1	events	20 / 280	while on treatment; safety; R0011754:Table 2
A2	events	6 / 137	while on treatment; safety; R0011754:Table 2
A2	events	5 / 137	not stated; safety; R0011901:Table 2
A3	events	1 / 70	not stated; safety; R0011901:Table 2

Constipation (5 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	22 / 280	while on treatment; safety; R0011754:Table 2
A1	events	19 / 280	not stated; safety; R0011901:Table 2
A2	events	8 / 137	not stated; safety; R0011901:Table 2
A2	events	11 / 137	while on treatment; safety; R0011754:Table 2
A3	events	3 / 70	not stated; safety; R0011901:Table 2

Discontinuation due to gastrointestinal adverse events (5 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	1 / 280	not stated; safety; R0011754:Results
A1	events	1 / 280	not stated; safety; R0011901:Results
A2	events	5 / 137	not stated; safety; R0011901:Results
A2	events	4 / 137	not stated; safety; R0011754:Results
A3	events	0 / 70	not stated; safety; R0011901:Results

Gallbladder and biliary disease (8 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 280	not stated; safety; hyperplastic cholecystopathy; registry:adverse_events
A1	events	1 / 280	while on treatment; safety; bile duct stone; R0011754:Supplement Table S2
A1	events	2 / 280	not stated; safety; cholelithiasis; registry:adverse_events
A1	events	2 / 280	not stated; safety; gallbladder polyp; registry:adverse_events
A2	events	0 / 137	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	0 / 137	while on treatment; safety; bile duct stone; R0011754:Supplement Table S2
A2	events	0 / 137	not stated; safety; gallbladder polyp; registry:adverse_events
A2	events	0 / 137	not stated; safety; hyperplastic cholecystopathy; registry:adverse_events

Acute pancreatitis (5 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 280	not stated; safety; R0011901:Results
A1	events	0 / 280	not stated; safety; R0011754:Results
A2	events	0 / 137	not stated; safety; R0011754:Results
A2	events	0 / 137	not stated; safety; R0011901:Results
A3	events	0 / 70	not stated; safety; R0011901:Results

Diabetic retinopathy complications (2 lines; O33)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 280	not stated; safety; diabetic retinopathy; registry:adverse_events
	A2	events				2 / 137	not stated; safety; diabetic retinopathy; registry:adverse_events

Death by suicide (5 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 280	while on treatment; safety; R0011754:Table 2
A1	events	0 / 280	not stated; safety; R0011901:Table 2
A2	events	0 / 137	not stated; safety; R0011901:Table 2
A2	events	0 / 137	while on treatment; safety; R0011754:Table 2
A3	events	0 / 70	not stated; safety; R0011901:Table 2

Pancreatic cancer (5 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	0 / 280	not stated; safety; R0011901:Supplement Table S2
A1	events	0 / 280	while on treatment; safety; R0011754:Supplement Table S2
A2	events	1 / 137	while on treatment; safety; R0011754:Supplement Table S2
A2	events	1 / 137	not stated; safety; R0011901:Supplement Table S2
A3	events	0 / 70	not stated; safety; R0011901:Supplement Table S2