factorial randomized trial

DECREASE

Combined Effects of SGLT2 Inhibition and GLP-1 Receptor Agonism on Food Intake, Body Weight and Central Satiety and Reward Circuits in Obese T2DM Patients

Type 2 diabetes (adults)NCT03361098S000930

Design

Randomized: 65
Start year: 2017
Treatment: 16 weeks, follow-up 16 weeks
Countries: Netherlands (1 sites)
Sponsor: Amsterdam UMC, location VUmc (industry)
Eligibility: age 18 to 75; BMI over 27; HbA1c 7 to 10 percent on metformin or 7.5 to 10 on metformin plus SU

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: randomized
Missing data: linear mixed model

Arms

Arm	Treatment	Background	Randomized
A1	Dapagliflozin Dapagliflozin with exenatide placebo	metformin with or without sulfonylurea; lifestyle: not reported	16
A2	Exenatide 10 ug subcutaneous twice daily Exenatide with dapagliflozin placebo	metformin with or without sulfonylurea; lifestyle: not reported	17
A3	exenatide and dapagliflozin Dapagliflozin plus exenatide	metformin with or without sulfonylurea; lifestyle: not reported	16
A4	Placebo Double placebo	metformin with or without sulfonylurea; lifestyle: not reported	16

Baseline characteristics

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

Characteristic	Statistic	Dapagliflozin A1	Exenatide 10 ug subcutaneous twice daily A2	Dapagliflozin plus exenatide A3	Placebo A4
age	mean (years)	64	65	64	60.9
age	sd (years)	8.4	5.8	7.4	7.2
bmi	mean (kg/m2)	31.7	32.7	30.9	31.5
bmi	sd (kg/m2)	3.3	5.1	3.4	5.9
diabetes duration	median (years)	8.0	10.0	7.0	9.5
diabetes duration	q1 (years)	5.5	6	5	7
diabetes duration	q3 (years)	13.5	18	12.8	10.5
egfr	mean (mL/min/1.73 m2)	83.4	83.2	88.8	87.8
egfr	sd (mL/min/1.73 m2)	14.6	13.7	10.6	11.2
female	n	4	6	4	4
female	percent	25	35.3	25	25.0
hba1c	mean (percent)	7.8	7.9	8.0	8.0
hba1c	sd (percent)	0.6	0.8	1.3	0.95
metformin use	n	16	17	16	16
metformin use	percent	100	100	100	100
other sulfonylurea use	n	5	6	3	8
other sulfonylurea use	percent	31.3	35.3	18.8	50.0
other uaer: less than 30	n	11	12	9	12
other uaer: less than 30	percent	68.8	70.6	56.3	70.6
other uaer: more than 30	n	5	5	7	5
other uaer: more than 30	percent	31.2	29.4	43.8	29.4
sbp	mean (mmHg)	136.4	132.1	130.3	132.6
sbp	sd (mmHg)	10.7	11.1	10.8	13.2
uacr	median (mg/mmol)	1.3	1.0	1.9	0.7
uacr	q1 (mg/mmol)	0.5	0.3	1.2	0.5
uacr	q3 (mg/mmol)	2.7	2.4	3.5	3.1
waist	mean (cm)	114.1	109.5	109.2	113.8
waist	sd (cm)	9.1	7.6	7.9	18.8
weight	mean (kg)	97.8	96.6	93.6	99.1
weight	sd (kg)	15.4	13.3	13.4	21.9

Results

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

HbA1c change (7 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Detail
16	A1	change	-8.6 mmol/mol		-12.1 to -5.2	not stated; other; R0010478:Results
16	A2	change	-11.9 mmol/mol		-15.2 to -8.5	not stated; other; R0010478:Results
16	A3	change	-15.5 mmol/mol		-19.0 to -12.0	not stated; other; R0010478:Results
16	A3 vs A4	md	-1.2 percent	0.19		not stated; randomized; R0008399:Results
16	A4	change	-3.4 mmol/mol		-7.0 to 0.1	not stated; other; R0010478:Results
16	A4 vs A1	md	0.5 percent	0.19		not stated; randomized; R0008399:Results
16	A4 vs A2	md	0.8 percent	0.18		not stated; randomized; R0008399:Results

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Detail
16	A1	change	-2.8 kg		-3.9 to -1.8	not stated; other; R0010478:Results
16	A1 vs A4	md	-2.5 kg	0.6		not stated; randomized; R0008399:Supplement Table 1
16	A2	change	-1.7 kg		-2.7 to -0.7	not stated; other; R0010478:Results
16	A2 vs A4	md	-1.4 kg	0.5		not stated; randomized; R0008399:Results
16	A3	change	-3.0 kg		-4.1 to -1.9	not stated; other; R0010478:Results
16	A3 vs A4	md	-2.8 kg	0.5		not stated; randomized; R0008399:Results
16	A4	change	-0.4 kg		-1.4 to 0.7	not stated; other; R0010478:Results

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

Arm	Statistic	Events / N	Detail
A1	events	0 / 16	not stated; randomized; R0008399:Results
A1	events	0 / 16	not stated; randomized; R0008399:Results
A1	events	0 / 16	not stated; randomized; R0008399:Results
A2	events	1 / 17	not stated; randomized; R0008399:Results
A3	events	0 / 16	not stated; randomized; R0008399:Results
A3	events	0 / 16	not stated; randomized; R0008399:Results
A3	events	0 / 16	not stated; randomized; R0008399:Results
A4	events	0 / 16	not stated; randomized; R0008399:Results
A4	events	0 / 16	not stated; randomized; R0008399:Results
A4	events	0 / 16	not stated; randomized; R0008399:Results

Level 2 or 3 hypoglycemia (episode rate) (4 lines; O04B)

Arm	Statistic	Detail
A1	rate	not stated; other; R0008399:Results
A2	rate	not stated; other; R0008399:Results
A3	rate	not stated; other; R0008399:Results
A4	rate	not stated; other; R0008399:Results

Systolic blood pressure change (11 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
16	A1	change	-4.4 mmHg	2.7	14	not stated; per protocol; R0008648:Table 2
16	A1 vs A4	md	-1.0 mmHg	3.2		not stated; randomized; R0008399:Supplement Table 1
16	A1 vs A4	md	-1.8 mmHg	3.0		not stated; per protocol; R0008648:Table 2
16	A2	change	-1.3 mmHg	2.1	17	not stated; per protocol; R0008648:Table 2
16	A2 vs A4	md	1.5 mmHg	3.2		not stated; randomized; R0008399:Supplement Table 1
16	A2 vs A4	md	0.5 mmHg	2.8		not stated; per protocol; R0008648:Table 2
16	A3	change	-6.8 mmHg	2.4	12	not stated; per protocol; R0008648:Table 2
16	A3 vs A4	md	-6.7 mmHg	3.1		not stated; per protocol; R0008648:Table 2
16	A3 vs A4	md	-6.1 mmHg	3.3		not stated; randomized; R0008399:Supplement Table 1
16	A4	change	-1.4 mmHg	2.4	13	not stated; per protocol; R0008648:Table 2
16	A4 vs A3	md	6.1 mmHg			not stated; other; R0010478:Results

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 16	not stated; randomized; R0008399:Results
A2	events	0 / 17	not stated; randomized; R0008399:Results
A3	events	0 / 16	not stated; randomized; R0008399:Results
A4	events	0 / 16	not stated; randomized; R0008399:Results

Hospitalization for heart failure (4 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 16	not stated; randomized; R0008399:Results
A2	events	0 / 17	not stated; randomized; R0008399:Results
A3	events	0 / 16	not stated; randomized; R0008399:Results
A4	events	0 / 16	not stated; randomized; R0008399:Results

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	0 / 16	not stated; randomized; R0008399:Results
A2	events	0 / 17	not stated; randomized; R0008399:Results
A3	events	0 / 16	not stated; randomized; R0008399:Results
A4	events	0 / 16	not stated; randomized; R0008399:Results

Discontinuation due to adverse events (8 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 16	not stated; randomized; R0008399:Results
A1	events	0 / 16	not stated; randomized; R0008399:Results
A2	events	0 / 17	not stated; randomized; R0008399:Results
A2	events	0 / 17	not stated; randomized; R0008399:Results
A3	events	1 / 16	not stated; randomized; R0008648:Figure 1
A3	events	1 / 16	not stated; randomized; R0008399:Results
A4	events	0 / 16	not stated; randomized; R0008399:Results
A4	events	0 / 16	not stated; randomized; R0008399:Results

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	1 / 16	not stated; randomized; nausea/vomiting; R0008399:Supplement Table 3
A2	events	3 / 17	not stated; randomized; nausea/vomiting; R0008399:Supplement Table 3
A3	events	6 / 16	not stated; randomized; nausea/vomiting; R0008399:Supplement Table 3
A4	events	1 / 16	not stated; randomized; nausea/vomiting; R0008399:Supplement Table 3

Discontinuation due to gastrointestinal adverse events (8 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	0 / 16	not stated; randomized; nausea; R0008399:Results
A1	events	0 / 16	not stated; randomized; nausea; R0008399:Results
A2	events	0 / 17	not stated; randomized; nausea; R0008399:Results
A2	events	0 / 17	not stated; randomized; nausea; R0008399:Results
A3	events	1 / 16	not stated; randomized; nausea; R0008648:Figure 1
A3	events	1 / 16	not stated; randomized; nausea; R0008399:Results
A4	events	0 / 16	not stated; randomized; nausea; R0008399:Results
A4	events	0 / 16	not stated; randomized; nausea; R0008399:Results

Death by suicide (4 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 16	not stated; randomized; R0008399:Results
A2	events	0 / 17	not stated; randomized; R0008399:Results
A3	events	0 / 16	not stated; randomized; R0008399:Results
A4	events	0 / 16	not stated; randomized; R0008399:Results