parallel randomized trial

NCT01144338

Exenatide Study of Cardiovascular Event Lowering Trial (EXSCEL). A Randomized, Placebo Controlled Clinical Trial to Evaluate Cardiovascular Outcomes After Treatment With Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus.

Type 2 diabetes (adults)NCT01144338S000905

Design

Randomized: 14,752
Start year: 2010
Treatment
Countries: multinational (687 sites)
Sponsor: AstraZeneca (industry)
Eligibility: age 18 or older; HbA1c 6.5 to 10.0 percent; eGFR 30 or more

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: yes
Primary estimand: not stated
Analysis population: randomized
Missing data

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Placebo Placebo	usual care glucose lowering therapy; lifestyle: not reported	7,396	7,396
A2	Exenatide extended release 2 mg subcutaneous once weekly Exenatide once weekly 2 mg	usual care glucose lowering therapy; lifestyle: not reported	7,356	7,356

Baseline characteristics

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

Characteristic	Statistic	Placebo A1	Exenatide extended release 2 mg subcutaneous once weekly A2	Whole trial ALL
age	mean (years)	61.9	61.8
age	sd (years)	9.4	9.4
asian	n	727	725
asian	percent	9.8	9.9
black	n	436	442
black	percent	5.9	6.0
bmi	mean (kg/m2)	32.7	32.6
bmi	sd (kg/m2)	6.4	6.3
diabetes duration	median (years)			12
diabetes duration	q1 (years)			7
diabetes duration	q3 (years)			18
egfr	mean (mL/min/1.73 m2)	76.6	77.1
egfr	sd (mL/min/1.73 m2)	24.0	23.5
established cvd	n	5388	5394
female	n	2809	2794
female	percent	38	38
hba1c	mean (percent)	8.1	8.1
hba1c	sd (percent)	1.0	1.0
hispanic	n	557	577
insulin use	n	3242	3216
insulin use	percent	47	46
metformin use	n	5297	5296
metformin use	percent	77	77
other dpp4i use	n	1027	1049
other dpp4i use	percent	15	15
other race american indian alaska native	n	35	38
other race native hawaiian pacific islander	n	17	18
other race other	n	612	635
other race other	percent	8.3	8.6
other sulfonylurea use	n	2522	2547
other sulfonylurea use	percent	37	37
other tzd use	n	268	283
other tzd use	percent	4	4
sbp	mean (mmHg)	135.5	135.4
sbp	sd (mmHg)	16.9	16.9
sglt2i use	n	24	44
sglt2i use	percent	0	1
uacr	median (mg/g)	23.8	22.9
uacr	q1 (mg/g)	13.5	11.6
uacr	q3 (mg/g)	35.1	34.1
weight	mean (kg)	92	92
weight	sd (kg)	21	22
white	n	5621	5554
white	percent	76.0	75.5

Analyses this trial contributes to

Results

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

HbA1c change (7 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Detail
26.07	A2 vs A1	md	-0.79 percent	-0.84 to -0.74	not stated; other; R0025168:Results
26.07	A2 vs A1	md	-0.66 percent	-0.79 to -0.54	not stated; other; race:other; R0023223:Table 3
26.07	A2 vs A1	md	-0.54 percent	-0.58 to -0.49	not stated; other; race:white; R0023223:Table 3
26.07	A2 vs A1	md	-0.7 percent		not stated; other; R0012068:Table 1
26.07	A2 vs A1	md	-0.63 percent	-0.75 to -0.53	not stated; other; race:asian; R0023223:Table 3
26.07	A2 vs A1	md	-0.63 percent	-0.77 to -0.46	not stated; other; race:black; R0023223:Table 3
52.14	A2 vs A1	md	-0.4 percent		not stated; other; R0012068:Table 1

Body weight change in kilograms (diabetes) (2 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26.07	A2 vs A1	md	-1.0 kg				not stated; other; R0012068:Table 1
52.14	A2 vs A1	md	-1.4 kg				not stated; other; R0012068:Table 1

Systolic blood pressure change (2 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
26.07	A2 vs A1	md	-1.2 mmHg				not stated; other; R0012068:Table 1
52.14	A2 vs A1	md	-2.0 mmHg				not stated; other; R0012068:Table 1

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 7372	not stated; safety; registry:adverse_events
	A2	events				0 / 7344	not stated; safety; registry:adverse_events

All cause mortality (3 lines; O20)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			584 / 7396	not stated; randomized; R0025316:Methods
A2	events			507 / 7356	not stated; randomized; R0025316:Methods
A2 vs A1	hr	0.86	0.77 to 0.97		not stated; randomized; R0025316:Methods

Three point MACE (5 lines; O21)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			905 / 7396	not stated; randomized; R0025316:Methods
A2 vs A1	hr	0.93	0.84 to 1.03		not stated; other; background:metformin; R0007143:Figure 4A
A2	events			839 / 7356	not stated; randomized; R0025316:Methods
A2 vs A1	hr	0.91	0.83 to 1.00		not stated; randomized; R0025316:Methods
A2 vs A1	hr	0.84	0.69 to 1.03		not stated; other; background:no_metformin; R0007143:Figure 4B

Kidney composite with 40 percent eGFR decline (3 lines; O22B)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			241 / 7396	not stated; randomized; R0025168:Results
A2	events			213 / 7356	not stated; randomized; R0025168:Results
A2 vs A1	hr	0.86	0.72 to 1.04		not stated; randomized; R0025168:Results

Kidney composite including albuminuria or smaller eGFR declines (3 lines; O22E)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			546 / 7396	not stated; randomized; R0025168:Results
A2	events			489 / 7356	not stated; randomized; R0025168:Results
A2 vs A1	hr	0.87	0.73 to 0.99		not stated; randomized; R0025168:Results

Hospitalization for heart failure (3 lines; O23)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			231 / 7396	not stated; randomized; registry:outcomes
A2	events			219 / 7356	not stated; randomized; registry:outcomes
A2 vs A1	hr	0.94	0.78 to 1.13		not stated; randomized; registry:outcomes

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1222 / 7372	not stated; safety; registry:adverse_events
	A2	events				1234 / 7344	not stated; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 7372	not stated; safety; registry:adverse_events
	A2	events				2 / 7344	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (8 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 7372	not stated; safety; biliary colic; registry:adverse_events
A1	events	1 / 7372	not stated; safety; biliary cyst; registry:adverse_events
A1	events	0 / 7372	not stated; safety; gallbladder fistula; registry:adverse_events
A1	events	1 / 7372	not stated; safety; gallbladder polyp; registry:adverse_events
A2	events	1 / 7344	not stated; safety; biliary colic; registry:adverse_events
A2	events	0 / 7344	not stated; safety; biliary cyst; registry:adverse_events
A2	events	1 / 7344	not stated; safety; gallbladder fistula; registry:adverse_events
A2	events	0 / 7344	not stated; safety; gallbladder polyp; registry:adverse_events

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				22 / 7372	not stated; safety; pancreatitis; registry:adverse_events
	A2	events				37 / 7344	not stated; safety; pancreatitis; registry:adverse_events

Thyroid cancer (any) (4 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	7 / 7372	not stated; safety; registry:adverse_events
A1	events	0 / 7372	not stated; safety; papillary thyroid cancer; registry:adverse_events
A2	events	14 / 7344	not stated; safety; registry:adverse_events
A2	events	1 / 7344	not stated; safety; papillary thyroid cancer; registry:adverse_events

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	1 / 7372	not stated; safety; blindness unilateral; registry:adverse_events
A1	events	2 / 7372	not stated; safety; vitreous haemorrhage; registry:adverse_events
A2	events	1 / 7344	not stated; safety; blindness unilateral; registry:adverse_events
A2	events	3 / 7344	not stated; safety; vitreous haemorrhage; registry:adverse_events

Suicidal ideation or behavior (6 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 7372	not stated; safety; depression suicidal; registry:adverse_events
A1	events	1 / 7372	not stated; safety; suicidal ideation; registry:adverse_events
A1	events	2 / 7372	not stated; safety; suicide attempt; registry:adverse_events
A2	events	1 / 7344	not stated; safety; depression suicidal; registry:adverse_events
A2	events	2 / 7344	not stated; safety; suicidal ideation; registry:adverse_events
A2	events	1 / 7344	not stated; safety; suicide attempt; registry:adverse_events

Gastroparesis (2 lines; O37A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 7372	not stated; safety; impaired gastric emptying; registry:adverse_events
	A2	events				1 / 7344	not stated; safety; impaired gastric emptying; registry:adverse_events

Intestinal obstruction or ileus (12 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	3 / 7372	not stated; safety; registry:adverse_events
A1	events	2 / 7372	not stated; safety; gastrointestinal obstruction; registry:adverse_events
A1	events	2 / 7372	not stated; safety; ileus; registry:adverse_events
A1	events	0 / 7372	not stated; safety; postoperative ileus; registry:adverse_events
A1	events	8 / 7372	not stated; safety; small intestinal obstruction; registry:adverse_events
A1	events	2 / 7372	not stated; safety; subileus; registry:adverse_events
A2	events	4 / 7344	not stated; safety; registry:adverse_events
A2	events	3 / 7344	not stated; safety; gastrointestinal obstruction; registry:adverse_events
A2	events	3 / 7344	not stated; safety; ileus; registry:adverse_events
A2	events	1 / 7344	not stated; safety; postoperative ileus; registry:adverse_events
A2	events	7 / 7344	not stated; safety; small intestinal obstruction; registry:adverse_events
A2	events	0 / 7344	not stated; safety; subileus; registry:adverse_events

Pancreatic cancer (2 lines; O38)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				15 / 7372	not stated; safety; registry:adverse_events
	A2	events				15 / 7344	not stated; safety; registry:adverse_events

eGFR total slope (3 lines; O51)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
166.98	A1	slope	-0.89 mL/min/1.73 m2 per year	0.04		6906	not stated; other; R0009730:Supplement Table S2
166.98	A2	slope	-0.88 mL/min/1.73 m2 per year	0.04		6920	not stated; other; R0009730:Supplement Table S2
166.98	A2 vs A1	md	0.01 mL/min/1.73 m2 per year		-0.11 to 0.13		not stated; other; R0009730:Supplement Table S2