parallel randomized trial

NCT02113332

Addition of Liraglutide to Overweight Patients With Type 2 Diabetes Treated With Multiple Daily Insulin Injections (MDI) With Inadequate Glycaemic Control

Type 2 diabetes (adults)NCT02113332S002357

Design

Randomized: 124
Start year: 2013
Treatment: 24 weeks, follow-up 24 weeks
Countries: Sweden (14 sites)
Sponsor: NU Hospital Group (industry)
Eligibility: T2D on multiple daily insulin injections; HbA1c 7.5 to 11.5 percent; BMI 27.5 to 45 kg/m2

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: hypothetical
Analysis population: full analysis
Missing data: LOCF

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Liraglutide 1.8 mg subcutaneous once daily Liraglutide	multiple daily insulin injections with or without metformin; lifestyle: not reported	64	63
A2	Placebo Placebo	multiple daily insulin injections with or without metformin; lifestyle: not reported	60	59

Baseline characteristics

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

Characteristic	Statistic	Liraglutide 1.8 mg subcutaneous once daily A1	Placebo A2
age	mean (years)	63.7	63.5
age	sd (years)	8.2	7.7
bmi	mean (kg/m2)	33.7	33.5
bmi	sd (kg/m2)	4.3	4.0
diabetes duration	mean (years)	17.3	17.0
diabetes duration	sd (years)	7.6	8.1
established cvd: coronary artery bypass grafting	n	5	7
established cvd: coronary artery bypass grafting	percent	7.8	11.7
established cvd: myocardial infarction	n	6	10
established cvd: myocardial infarction	percent	9.4	16.7
established cvd: percutaneous coronary intervention	n	5	8
established cvd: percutaneous coronary intervention	percent	7.8	13.3
established cvd: stroke	n	1	0
established cvd: stroke	percent	1.6	0.0
female	n	24	20
female	percent	37.5	33.3
hba1c	mean (percent)	9.0	9.0
hba1c	sd (percent)	1.0	1.1
hispanic	n	2	0
hispanic	percent	3.1	0.0
insulin dose	mean (U/day)	105.3	105.7
insulin dose	sd (U/day)	44.5	41.2
metformin use	n	44	44
metformin use	percent	68.8	73.3
other race american indian alaska native	n	1	0
other race american indian alaska native	percent	1.6	0.0
sbp	mean (mmHg)	137.9	134.1
sbp	sd (mmHg)	16.6	13.9
waist	mean (cm)	116.1	115.7
waist	sd (cm)	10.2	10.6
weight	mean (kg)	98.9	100.0
weight	sd (kg)	14.0	14.8
white	n	63	60
white	percent	98.4	100.0

Analyses this trial contributes to

Results

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

HbA1c change (11 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
24	A1	change	-1.55 percent	0.95		63	hypothetical; full analysis; R0026157:Table 2
24	A1	change	-1.52 percent	0.11	-1.74 to -1.30	64	hypothetical; randomized; R0026157:Supplement eTable 3
24	A1 vs A2	md	-1.13 percent		-1.45 to -0.81		hypothetical; full analysis; R0026157:Table 2
24	A1	change	-1.54 percent	0.11	-1.77 to -1.32	63	hypothetical; full analysis; R0026157:Table 2
24	A1 vs A2	md	-1.10 percent		-1.42 to -0.78		hypothetical; randomized; R0026157:Supplement eTable 3
24	A1 vs A2	md	-1.14 percent		-1.47 to -0.80		hypothetical; per protocol; R0026157:Supplement eTable 2
24	A1	change	-1.53 percent	0.12	-1.76 to -1.30		hypothetical; per protocol; R0026157:Supplement eTable 2
24	A2	change	-0.42 percent	0.12	-0.65 to -0.19	59	hypothetical; full analysis; R0026157:Table 2
24	A2	change	-0.41 percent	0.12	-0.64 to -0.18	60	hypothetical; randomized; R0026157:Supplement eTable 3
24	A2	change	-0.42 percent	0.89		59	hypothetical; full analysis; R0026157:Table 2
24	A2	change	-0.398 percent	0.119	-0.64 to -0.16		hypothetical; per protocol; R0026157:Supplement eTable 2

Body weight change in kilograms (diabetes) (11 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
24	A1 vs A2	md	-3.77 kg		-4.85 to -2.69		hypothetical; per protocol; R0026157:Supplement eTable 2
24	A1	change	-3.77 kg	0.37	-4.50 to -3.03	63	hypothetical; full analysis; R0026157:Table 2
24	A1	change	-3.71 kg	0.37	-4.43 to -2.98	64	hypothetical; randomized; R0026157:Supplement eTable 3
24	A1	change	-3.77 kg	3.10		63	hypothetical; full analysis; R0026157:Table 2
24	A1	change	-3.79 kg	0.38	-4.55 to -3.04		hypothetical; per protocol; R0026157:Supplement eTable 2
24	A1 vs A2	md	-3.81 kg		-4.87 to -2.76		hypothetical; full analysis; R0026157:Table 2
24	A1 vs A2	md	-3.75 kg		-4.80 to -2.71		hypothetical; randomized; R0026157:Supplement eTable 3
24	A2	change	0.049 kg	0.38	-0.71 to 0.81	59	hypothetical; full analysis; R0026157:Table 2
24	A2	change	0.05 kg	0.38		60	hypothetical; randomized; R0026157:Supplement eTable 3
24	A2	change	0.058 kg	2.74		59	hypothetical; full analysis; R0026157:Table 2
24	A2	change	-0.024 kg	0.390	-0.796 to 0.748		hypothetical; per protocol; R0026157:Supplement eTable 2

HbA1c below 7 percent (6 lines; O03)

Week	Arm	Statistic	Events / N	Detail
24	A1	responders	27 / 63	hypothetical; full analysis; R0026157:Table 2
24	A1	responders	27 / 64	hypothetical; randomized; R0026157:Supplement eTable 3
24	A1	responders	26 / 58	hypothetical; per protocol; R0026157:Supplement eTable 2
24	A2	responders	3 / 59	hypothetical; full analysis; R0026157:Table 2
24	A2	responders	3 / 60	hypothetical; randomized; R0026157:Supplement eTable 3
24	A2	responders	3 / 55	hypothetical; per protocol; R0026157:Supplement eTable 2

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 63	hypothetical; full analysis; R0026157:Results
	A2	events				0 / 59	hypothetical; full analysis; R0026157:Results

Level 2 or 3 hypoglycemia (episode rate) (10 lines; O04B)

Arm	Statistic	Estimate	Events / N	Detail
A1	rate	0.0	63	hypothetical; full analysis; R0026157:Table 2
A1	rate	0.37	63	hypothetical; full analysis; R0026157:Table 2
A1	rate	1.29	63	hypothetical; full analysis; R0026157:Table 2
A1	rate	0.079	63	hypothetical; full analysis; R0026157:Table 2
A1	rate		63	hypothetical; full analysis; R0026157:Table 2
A2	rate	1.24	59	hypothetical; full analysis; R0026157:Table 2
A2	rate	0.0	59	hypothetical; full analysis; R0026157:Table 2
A2	rate	0.25	59	hypothetical; full analysis; R0026157:Table 2
A2	rate		59	hypothetical; full analysis; R0026157:Table 2
A2	rate	0.051	59	hypothetical; full analysis; R0026157:Table 2

Systolic blood pressure change (11 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
24	A1	change	-4.62 mmHg	1.53	-7.65 to -1.59	61	hypothetical; full analysis; R0026157:Table 2
24	A1	change	-4.70 mmHg	1.46	-7.60 to -1.80	64	hypothetical; randomized; R0026157:Supplement eTable 3
24	A1	change	-5.69 mmHg	13.38		61	hypothetical; full analysis; R0026157:Table 2
24	A1	change	-4.08 mmHg	1.59	-7.22 to -0.93	56	hypothetical; per protocol; R0026157:Supplement eTable 2
24	A1 vs A2	md	-5.47 mmHg		-9.85 to -1.10		hypothetical; full analysis; R0026157:Table 2
24	A1 vs A2	md	-5.84 mmHg		-10.03 to -1.66		hypothetical; randomized; R0026157:Supplement eTable 3
24	A1 vs A2	md	-5.01 mmHg		-9.53 to -0.48		hypothetical; per protocol; R0026157:Supplement eTable 2
24	A2	change	0.86 mmHg	1.57	-2.25 to 3.97	58	hypothetical; full analysis; R0026157:Table 2
24	A2	change	1.14 mmHg	1.51	-1.85 to 4.14	60	hypothetical; randomized; R0026157:Supplement eTable 3
24	A2	change	1.98 mmHg	13.32		58	hypothetical; full analysis; R0026157:Table 2
24	A2	change	0.930 mmHg	1.617	-2.275 to 4.135	54	hypothetical; per protocol; R0026157:Supplement eTable 2

Hospitalization for heart failure (2 lines; O23)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 64	not stated; safety; cardiac failure; R0026157:Table 3
	A2	events				1 / 60	not stated; safety; cardiac failure; R0026157:Table 3

Health related quality of life total score (any instrument) (15 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
24	A1	change	4.48 points	0.76	2.98 to 5.98	60	hypothetical; full analysis; R0026157:Table 2
24	A1	change	4.23 points	0.77	2.71 to 5.74	63	hypothetical; randomized; R0026157:Supplement eTable 3
24	A1	change	4.85 points	6.89		60	hypothetical; full analysis; R0026157:Table 2
24	A1	change	4.75 points	0.79	3.19 to 6.31	55	hypothetical; per protocol; R0026157:Supplement eTable 2
24	A1	final	13.8 points	4.5		58	hypothetical; full analysis; R0026157:Table 2
24	A1	final	13.7 points	4.6		55	hypothetical; per protocol; R0026157:Supplement eTable 2
24	A1 vs A2	md	3.09 points		0.94 to 5.25		hypothetical; full analysis; R0026157:Table 2
24	A1 vs A2	md	2.84 points		0.66 to 5.03		hypothetical; randomized; R0026157:Supplement eTable 3
24	A1 vs A2	md	3.22 points		1.00 to 5.45		hypothetical; per protocol; R0026157:Supplement eTable 2
24	A2	change	1.39 points	0.78	-0.15 to 2.93	57	hypothetical; full analysis; R0026157:Table 2
24	A2	change	1.38 points	0.79	-0.18 to 2.95	59	hypothetical; randomized; R0026157:Supplement eTable 3
24	A2	change	1.00 points	8.10		57	hypothetical; full analysis; R0026157:Table 2
24	A2	change	1.53 points	0.79	-0.05 to 3.11	54	hypothetical; per protocol; R0026157:Supplement eTable 2
24	A2	final	10.0 points	6.8		56	hypothetical; full analysis; R0026157:Table 2
24	A2	final	9.98 points	6.84		52	hypothetical; per protocol; R0026157:Supplement eTable 2

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				3 / 64	not stated; safety; R0026157:Table 3
	A2	events				4 / 60	not stated; safety; R0026157:Table 3

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 64	not stated; randomized; gastrointestinal symptoms; R0026157:Figure 1
	A2	events				2 / 60	not stated; randomized; R0026157:Figure 1

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				21 / 64	not stated; safety; R0026157:Results
	A2	events				1 / 60	not stated; safety; R0026157:Results

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				5 / 64	not stated; safety; R0026157:Results
	A2	events				3 / 60	not stated; safety; R0026157:Results

Discontinuation due to gastrointestinal adverse events (1 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 64	not stated; randomized; gastrointestinal symptoms; R0026157:Figure 1

Gallbladder and biliary disease (2 lines; O28)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 64	not stated; safety; cholecystitis; R0026157:Table 3
	A2	events				1 / 60	not stated; safety; cholecystitis; R0026157:Table 3