parallel randomized trial

NCT02750410

A Phase 4 Study of Efficacy and Safety of Dulaglutide When Added to Insulin Treatment With or Without Oral Antidiabetic Medication in Patients With Type 2 Diabetes

Type 2 diabetes (adults)NCT02750410S001247

Design

Randomized: 159
Start year: 2016
Treatment: 16 weeks, follow-up 16 weeks
Countries: Japan (26 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: Japanese adults 20 years or older; HbA1c 7.5 to 10.5 percent on insulin over 10 U/day; BMI 18.5 to 35

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: full analysis
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Placebo Placebo	stable insulin (basal, premixed or basal bolus) with or without one or two oral drugs, doses unchanged; lifestyle: not reported	39	39	37
A2	Dulaglutide 0.75 mg subcutaneous once weekly Dulaglutide 0.75 mg	stable insulin (basal, premixed or basal bolus) with or without one or two oral drugs, doses unchanged; lifestyle: not reported	120	120	117

Baseline characteristics

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

Characteristic	Statistic	Placebo A1	Dulaglutide 0.75 mg subcutaneous once weekly A2
age	mean (years)	59.1	59.3
age	sd (years)	10.68	10.23
asian	n	39	120
asian	percent	100	100
black	n	0	0
bmi	mean (kg/m2)	26.7	26.13
bmi	sd (kg/m2)	3.68	3.65
diabetes duration	mean (years)	16.9	17.1
diabetes duration	sd (years)	7.7	8.6
egfr: 30 to less than 45	n	1	6
egfr: 30 to less than 45	percent	2.6	5.0
egfr: 45 to less than 60	n	6	14
egfr: 45 to less than 60	percent	15.4	11.7
egfr: 60 to less than 90	n	24	72
egfr: 60 to less than 90	percent	61.5	60.0
egfr: 90 or more	n	8	28
egfr: 90 or more	percent	20.5	23.3
female	n	19	42
female	percent	48.7	35.0
hba1c	mean (percent)	8.64	8.50
hba1c	sd (percent)	0.72	0.69
hispanic	n	0	0
insulin dose background:basal_bolus_insulin	mean (U/day)	43.4	46.0
insulin dose background:basal_bolus_insulin	sd (U/day)	19.3	19.1
insulin dose background:basal_insulin	mean (U/day)	20.2	22.7
insulin dose background:basal_insulin	sd (U/day)	8.0	11.1
insulin dose background:premixed_insulin	mean (U/day)	37.2	33.9
insulin dose background:premixed_insulin	sd (U/day)	17.0	15.8
other background: none	n	12	47
other background: none	percent	30.8	39.2
other background: oad	n	27	73
other background: oad	percent	69.2	60.8
other fbg	mean (mg/dL)	172.5	158.3
other fbg	sd (mg/dL)	62.1	57.3
other insulin regimen: basal bolus	n	13	42
other insulin regimen: basal bolus	percent	33.3	35.0
other insulin regimen: basal	n	17	52
other insulin regimen: basal	percent	43.6	43.3
other insulin regimen: premixed	n	9	26
other insulin regimen: premixed	percent	23.1	21.7
other race american indian alaska native	n	0	0
other race multiple	n	0	0
other race native hawaiian pacific islander	n	0	0
weight	mean (kg)	70.7	70.5
weight	sd (kg)	11.4	11.8
white	n	0	0

Results

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

HbA1c change (12 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
16	A1	change	0.22 percent	0.15			not stated; full analysis; background:basal_insulin; R0023153:Results
16	A1	change	0.20 percent	0.21			not stated; full analysis; background:premixed_insulin; R0023153:Results
16	A1	change	0.06 percent	0.10		39	not stated; full analysis; R0023021:Results
16	A1	change	-0.27 percent	0.17			not stated; full analysis; background:basal_bolus_insulin; R0023153:Results
16	A2 vs A1	md	-1.62 percent		-1.96 to -1.28		not stated; full analysis; background:basal_insulin; R0023153:Results
16	A2	change	-1.45 percent	0.06		120	not stated; full analysis; R0023021:Results
16	A2	change	-1.42 percent	0.10			not stated; full analysis; background:basal_bolus_insulin; R0023153:Results
16	A2 vs A1	md	-1.15 percent		-1.54 to -0.77		not stated; full analysis; background:basal_bolus_insulin; R0023153:Results
16	A2	change	-1.40 percent	0.08			not stated; full analysis; background:basal_insulin; R0023153:Results
16	A2	change	-1.57 percent	0.12			not stated; full analysis; background:premixed_insulin; R0023153:Results
16	A2 vs A1	md	-1.78 percent		-2.25 to -1.30		not stated; full analysis; background:premixed_insulin; R0023153:Results
16	A2 vs A1	md	-1.50 percent		-1.73 to -1.28		not stated; full analysis; R0023021:Results

Body weight change in kilograms (diabetes) (13 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
16	A1	change	-0.30 kg	0.30		39	not stated; full analysis; R0023021:Results
16	A1	change	-0.74 kg	0.65			not stated; full analysis; background:premixed_insulin; R0023153:Results
16	A1	change	-0.30 kg	0.45			not stated; full analysis; background:basal_insulin; R0023153:Results
16	A1	change	0.05 kg	0.52			not stated; full analysis; background:basal_bolus_insulin; R0023153:Results
16	A2 vs A1	md	0.10 kg		-0.59 to 0.78		not stated; full analysis; registry:outcomes
16	A2	change	-0.20 kg	0.17		120	not stated; full analysis; R0023021:Results
16	A2 vs A1	md	-0.10 kg				not stated; full analysis; R0023021:Results
16	A2	change	-0.53 kg	0.29			not stated; full analysis; background:basal_bolus_insulin; R0023153:Results
16	A2 vs A1	md	-0.58 kg		-1.76 to 0.60		not stated; full analysis; background:basal_bolus_insulin; R0023153:Results
16	A2	change	0.17 kg	0.26			not stated; full analysis; background:basal_insulin; R0023153:Results
16	A2 vs A1	md	0.46 kg		-0.56 to 1.48		not stated; full analysis; background:basal_insulin; R0023153:Results
16	A2	change	-0.44 kg	0.37			not stated; full analysis; background:premixed_insulin; R0023153:Results
16	A2 vs A1	md	0.30 kg		-1.17 to 1.78		not stated; full analysis; background:premixed_insulin; R0023153:Results

HbA1c below 7 percent (5 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	responders	0		36	not stated; full analysis; R0023021:Results
16	A1	responders	47.4		36	not stated; full analysis; registry:outcomes
16	A1 vs A2	or	0.117	0.028 to 0.479		not stated; full analysis; registry:outcomes
16	A2	responders	47.4		116	not stated; full analysis; R0023021:Results
16	A2	responders	0		116	not stated; full analysis; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (8 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 39	not stated; safety; registry:adverse_events
A1	events	0 / 39	not stated; safety; R0023021:Results
A1	events	12 / 39	not stated; safety; R0023021:Results
A1	events	4 / 39	not stated; safety; R0023021:Results
A2	events	1 / 120	not stated; safety; R0023021:Results
A2	events	51 / 120	not stated; safety; R0023021:Results
A2	events	10 / 120	not stated; safety; R0023021:Results
A2	events	1 / 120	not stated; safety; registry:adverse_events

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 39	not stated; safety; R0023021:Table 2
	A2	events				0 / 120	not stated; safety; R0023021:Table 2

Hospitalization for heart failure (1 lines; O23)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 39	not stated; safety; R0023021:Table 2

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 39	not stated; safety; R0023021:Table 2
	A2	events				3 / 120	not stated; safety; R0023021:Table 2

Discontinuation due to adverse events (11 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	4 / 39	not stated; safety; R0023021:Table 2
A1	events	2 / 39	not stated; randomized; registry:flow
A1	events	2 / 39	not stated; safety; hyperglycemia; R0023021:Results
A1	events	1 / 39	not stated; safety; hypersensitivity; R0023021:Results
A1	events	1 / 39	not stated; safety; puncture site pain; R0023021:Results
A2	events	4 / 120	not stated; safety; R0023021:Table 2
A2	events	2 / 120	not stated; randomized; registry:flow
A2	events	1 / 120	not stated; safety; gastrointestinal disorder; R0023021:Results
A2	events	1 / 120	not stated; safety; injection site reaction; R0023021:Results
A2	events	1 / 120	not stated; safety; liver function test increased; R0023021:Results
A2	events	1 / 120	not stated; safety; myositis; R0023021:Results

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 39	not stated; safety; R0023021:Table 2
	A2	events				7 / 120	not stated; safety; R0023021:Table 2

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 39	not stated; safety; R0023021:Table 2
	A2	events				3 / 120	not stated; safety; R0023021:Table 2

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 39	not stated; safety; registry:adverse_events
	A2	events				5 / 120	not stated; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				4 / 39	not stated; safety; R0023021:Table 2
	A2	events				8 / 120	not stated; safety; R0023021:Table 2

Discontinuation due to gastrointestinal adverse events (2 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 39	not stated; safety; R0023021:Results
	A2	events				1 / 120	not stated; safety; R0023021:Results

Suicidal ideation or behavior (2 lines; O35A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 39	not stated; safety; suicide attempt; registry:adverse_events
	A2	events				0 / 120	not stated; safety; suicide attempt; registry:adverse_events

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 39	not stated; safety; R0023021:Table 2
	A2	events				0 / 120	not stated; safety; R0023021:Table 2