other randomized trial

NCT01744236

A Phase IV, Randomized, Double-blind, Placebo-controlled, Parallel-group Trial to Assess the Effect of 12-week Treatment With the Glucagon-like Peptide-1 Receptor Agonist (GLP-1RA) Liraglutide or Dipeptidyl Peptidase-4 Inhibitor (DPP-4i) Sitagliptin on the Cardiovascular, Renal and Gastrointestinal System in Insulin-naïve Patients With Type 2 Diabetes (T2DM).

Type 2 diabetes (adults)NCT01744236S002312

Design

Randomized: 57
Start year: 2013
Treatment: 12 weeks, follow-up 12 weeks
Countries: Netherlands (1 sites)
Sponsor: Amsterdam UMC, location VUmc (mixed)
Eligibility: age 35 to 75, BMI 25 to 40, HbA1c 6.5 to 9.0 percent, stable metformin and/or sulfonylurea, eGFR 60 or more

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: pharmacy or sealed
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: per protocol
Missing data: completers only

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Placebo Placebo infusion (acute study)	lifestyle: not reported	28	28
A2	exenatide Exenatide infusion (acute study)	lifestyle: not reported	29	24
A3	Sitagliptin Sitagliptin 100 mg (12 week study)	metformin and/or sulfonylurea; lifestyle: not reported	20	19
A4	Liraglutide 1.8 mg subcutaneous once daily Liraglutide 1.8 mg (12 week study)	metformin and/or sulfonylurea; lifestyle: not reported	19	19
A5	Placebo Placebo (12 week study)	metformin and/or sulfonylurea; lifestyle: not reported	17	17
A6	exenatide Exenatide infusion (MRI crossover)	lifestyle: not reported	12	12
A7	Placebo Placebo infusion (MRI crossover)	lifestyle: not reported	12	12

Baseline characteristics

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

Characteristic	Statistic	Placebo A1	Exenatide infusion (acute study) A2	Sitagliptin A3	Liraglutide 1.8 mg subcutaneous once daily A4	Placebo A5	Whole trial ALL
age cohort:mri_crossover	mean (years)						60.1
age cohort:mri_crossover	sd (years)						7.4
age	mean (years)	64.3	61.4	61.7	60.5	65.8
age	sd (years)	6.2	7.4	6.8	7.2	5.8
bmi cohort:mri_crossover	mean (kg/m2)						32.0
bmi cohort:mri_crossover	sd (kg/m2)						4.1
bmi	mean (kg/m2)	31.2	32.1	31.5	33.3	30.6
bmi	sd (kg/m2)	3.5	4.6	4.3	4.5	2.9
diabetes duration	mean (years)	8.6	7.3	8.1	7.7	8.2
diabetes duration	sd (years)	5.4	4.5	5.8	4.5	4.8
egfr	median (mL/min/1.73 m2)	91	93
egfr	q1 (mL/min/1.73 m2)	80	82
egfr	q3 (mL/min/1.73 m2)	112	103
hba1c cohort:mri_crossover	mean (percent)						7.4
hba1c cohort:mri_crossover	sd (percent)						0.7
hba1c	mean (percent)	7.3	7.3	7.1	7.4	7.5
hba1c	sd (percent)	0.7	0.6	0.5	0.7	0.7
metformin use	n	26	23	18	19	15
metformin use	percent	92.9	95.8	94.7	100	88.2
other male cohort:mri_crossover	n						12
other male	n	23	21	16	14	13
other male	percent	82.1	72.4	84.2	73.7	76.5
other sulfonylurea use cohort:mri_crossover	n						5
other sulfonylurea use	n	13	10	9	7	8
other sulfonylurea use	percent	46.4	41.7	47.4	36.8	47.1
sbp	mean (mmHg)	136.1	135.5	132.5	136.6	137.6
sbp	sd (mmHg)			12.4	17.0	14.9
sbp	se (mmHg)	3.0	2.6
uacr	median (mg/mmol)	1.04	0.93
uacr	q1 (mg/mmol)	0.45	0.47
uacr	q3 (mg/mmol)	1.80	3.21
waist cohort:mri_crossover	mean (cm)						111.8
waist cohort:mri_crossover	sd (cm)						8.9
waist	mean (cm)	111.7	111.7	111.7	114.9	107.8
waist	sd (cm)	8.1	13.7	13.1	11.7	7.2
weight	mean (kg)	98.8	101.3	99.3	105.9	95.8
weight	sd (kg)	11.6	19.1	17.2	17.2	9.8

Results

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

HbA1c change (9 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
12	A3	final	6.7 percent	0.1		17	not stated; per protocol; R0023036:Table 1
12	A3 vs A5	md	-0.8 percent		-1.4 to -0.4		not stated; per protocol; R0020426:Results
12	A3 vs A5	md	-0.91 percent	0.22			not stated; per protocol; R0023036:Table 1
12	A4	final	6.7 percent	0.2		17	not stated; per protocol; R0023036:Table 1
12	A4 vs A5	md	-1.3 percent		-1.7 to -0.9		not stated; per protocol; R0020426:Results
12	A4 vs A5	md	-1.26 percent	0.21			not stated; per protocol; R0023036:Table 1
12	A5	final	8.0 percent	0.3		17	not stated; per protocol; R0023036:Table 1
12	A5 vs A3	md	0.8 percent				not stated; per protocol; R0017471:Results
12	A5 vs A4	md	1.7 percent				not stated; per protocol; R0017471:Results

Body weight change in kilograms (diabetes) (7 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
12	A3	final	97.7 kg	4.5		17	not stated; per protocol; R0023036:Table 1
12	A3 vs A5	md	-0.8 kg		-2.7 to 1.0		not stated; per protocol; R0020426:Results
12	A3 vs A5	md	-0.57 kg	0.97			not stated; per protocol; R0023036:Table 1
12	A4	final	101.0 kg	3.1		17	not stated; per protocol; R0023036:Table 1
12	A4 vs A5	md	-1.7 kg		-3.6 to 0.3		not stated; per protocol; R0020426:Results
12	A4 vs A5	md	-1.89 kg	0.99			not stated; per protocol; R0023036:Table 1
12	A5	final	95.7 kg	2.5		17	not stated; per protocol; R0023036:Table 1

Level 2 or 3 hypoglycemia (participants) (1 lines; O04)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A6	events				1 / 12	not stated; safety; R0012378:Results

Systolic blood pressure change (9 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
0.01	A1	final	145 mmHg	4	28	not stated; other; R0013843:Table 2
0.01	A1	final	143.9 mmHg	3.8	28	not stated; other; R0017471:Table 1
0.01	A2	final	151 mmHg	4	24	not stated; other; R0013843:Table 2
0.01	A2	final	151.3 mmHg	3.2	29	not stated; other; R0017471:Table 1
0.01	A2 vs A1	md	7.3 mmHg			not stated; other; R0017471:Results
12	A3	final	132.1 mmHg	3.1	19	not stated; per protocol; R0017471:Table 2
12	A4	final	127.5 mmHg	4.9	19	not stated; per protocol; R0017471:Table 2
12	A5	final	139.7 mmHg	3.2	17	not stated; per protocol; R0017471:Table 2
12	A5 vs A4	md	11.5 mmHg			not stated; per protocol; R0017471:Results

Acute kidney injury (3 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Three point MACE (3 lines; O21)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Four point MACE including unstable angina (3 lines; O21B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Hospitalization for heart failure (3 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Heart failure events (3 lines; O23B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Discontinuation due to adverse events (6 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A3	events	1 / 20	not stated; randomized; R0020426:Results
A4	events	0 / 19	not stated; randomized; R0017471:Figure 1
A5	events	0 / 17	not stated; randomized; R0017471:Figure 1
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Nausea (7 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A2	events	4 / 24	not stated; other; R0013843:Results
A3	events	2 / 20	not stated; other; gastrointestinal disturbances (nausea, diarrhoea); R0020426:Results
A4	events	12 / 19	not stated; other; gastrointestinal disturbances (nausea, diarrhoea); R0020426:Results
A5	events	0 / 17	not stated; other; gastrointestinal disturbances (nausea, diarrhoea); R0020426:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Vomiting (3 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A2	events	1 / 24	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Constipation (3 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Discontinuation due to gastrointestinal adverse events (6 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A3	events	0 / 20	not stated; randomized; R0017471:Figure 1
A4	events	0 / 19	not stated; randomized; R0017471:Figure 1
A5	events	0 / 17	not stated; randomized; R0017471:Figure 1
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Gallbladder and biliary disease (3 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Acute pancreatitis (3 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Medullary thyroid carcinoma (3 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Thyroid cancer (any) (3 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Diabetic retinopathy complications (3 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Nonarteritic anterior ischemic optic neuropathy (3 lines; O34)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Suicidal ideation or behavior (3 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Death by suicide (3 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Gastroparesis (3 lines; O37A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Intestinal obstruction or ileus (3 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Pancreatic cancer (3 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results

Any cancer (3 lines; O39)

Arm	Statistic	Events / N	Detail
A1	events	0 / 28	not stated; other; R0013843:Results
A6	events	0 / 12	not stated; safety; R0012378:Results
A7	events	0 / 12	not stated; safety; R0012378:Results