Detailed
Information
The
REWIND study was an event-driven, randomized, double-blind, phase 3
CV outcomes study of dulaglutide.1
The
study evaluated the effect on MACE-3 and other serious outcomes with
once-weekly dulaglutide 1.5 mg treatment compared with placebo when
added to standard of care in participants 50 years of age and older
with T2DM and established CV disease and/or risk factors.1
Eligible
patients had
newly
diagnosed or established T2DM
an
HbA1c value of 9.5% or lower, and
vascular
diseases or CV risk factors depending on their age (Table
1).1,2
Table
1. Age-Specific Inclusion Criteria for REWIND Trial1
|
If
the participant's age was...
|
Then
they had to have...
|
|
50-54
y
|
established
CVD.
|
|
55-59
y
|
established
CVD or evidence of other subclinical CVD.
|
|
60
y or older
|
established
CVD, evidence of other subclinical CVD, or at least 2 other CV
risk factors.
|
Abbreviations:
CV = cardiovascular; CVD = cardiovascular disease; REWIND =
Researching cardiovascular Events with a Weekly INcretin in Diabetes.
Patients
were excluded if they had
liver
disease
a
history of pancreatitis
gastric
emptying abnormalities
an
eGFR of less than 15 mL/min/1.73m2
or on dialysis
a
coronary or cerebrovascular event in the last 2 months or plans to
revascularize, or
history
of medullary C-cell hyperplasia or medullary thyroid cancer.1,2
A
total of 9901 patients in 24 countries were randomized.2
More
detailed information on baseline characteristics is found in
Table
2. Baseline Characteristics of Patients Randomized in the REWIND
Study2
|
Clinical
Characteristics
|
Dulaglutide
n=4949
|
Placebo
n=4952
|
|
Age,
y, mean (SD)
|
66.2
(6.5)
|
66.2
(6.5)
|
|
Females,
n (%)
|
2306
(46.6)
|
2283
(46.1)
|
|
DM
duration, y, mean (SD)
|
10.5
(7.3)
|
10.6
(7.2)
|
|
HbA1c,
%, mean (SD)
|
7.3
(1.1)
|
7.4
(1.1)
|
|
BMI,
kg/m2,
mean (SD)
|
32.3
(5.7)
|
32.3
(5.8)
|
|
BP,
mmHg, mean (SD)
|
137.1
(16.6)/78.4 (9.8)
|
137.3
(17.0)/78.5 (9.9)
|
|
Pulse,
beats/min, mean (SD)
|
71.4
(10.7)
|
71.6
(11.0)
|
|
Cholesterol,
mmol/L [mg/dL], Mean (SD)
|
4.52
(1.16) [174.79 (44.86)]
|
4.52
(1.16) [174.79 (44.86)]
|
|
LDL
cholesterol, mmol/L [mg/dL], Mean (SD)
|
2.56
(0.98) [98.99 (37.90)]
|
2.56
(0.98) [98.99 (37.90)]
|
|
HDL
cholesterol, mmol/L [mg/dL], Mean (SD)
|
1.18
(0.33) [45.63 (12.76)]
|
1.18
(0.36) [45.63 (13.92)]
|
|
Median
triglycerides (IQR), mmol/L [mg/dL], Mean (SD)
|
1.60
(1.15-2.2) [141.72 (101.86-194.86)]
|
1.60
(1.20-2.25) [141.72 (106.29-199.30)]
|
|
eGFR<60
mL/min/1.73 m2,
n (%)
|
1081
(21.8)
|
1118
(22.6)
|
|
Albuminuria,
n (%)a
|
1707
(34.5)
|
1760
(35.5)
|
|
Prior
CV disease b,
n (%)
|
1560
(31.5)
|
1554
(31.4)
|
|
Prior
hypertension, n (%)
|
4605
(93.0)
|
4619
(93.3)
|
|
Prior
heart failure, n (%)
|
421
(8.5)
|
432
(8.7)
|
|
Prior
diabetic retinopathy, n (%)
|
448
(9.1)
|
443
(8.9)
|
|
Current
tobacco use, n (%)
|
694
(14.0)
|
713
(14.4)
|
Abbreviations:
BMI = body mass index; BP = blood pressure; CV = cardiovascular; DM =
diabetes mellitus; eGFR = estimated glomerular filtration rate; HbA1c
= glycated hemoglobin; HDL = high-density lipoprotein; IQR =
interquartile range; LDL = low-density lipoprotein; REWIND =
Researching cardiovascular Events with a Weekly INcretin in Diabetes.
a
UACR ≥30 mg/g
b
Myocardial infarction, ischemic stroke,unstable angina
with electrocardiogram changes, myocardial ischemia on imaging or
stress test, or coronary, carotid,or peripheral revascularization.
References
1.
Gerstein HC, Colhoun HM, Dagenais GR, et al. REWIND Trial
Investigators. Design and baseline characteristics of participants in
the Researching cardiovascular Events with a Weekly INcretin in
Diabetes (REWIND) trial on the cardiovascular effects of dulaglutide.
Diabetes Obes Metab. 2018;20(1):42-49.
https://doi.org/10.1111/dom.13028
2.
Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and
cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind,
randomised placebo-controlled trial. The Lancet.
2019;394(10193):121-130.
https://doi.org/10.1016/S0140-6736(19)31149-3
Glossary
CV =
cardiovascular
CVD
= cardiovascular disease
eGFR
= estimated glomerular filtration rate
HbA1c
= glycated hemoglobin
MACE-3
= major adverse cardiovascular events (death due to cardiovascular
causes, nonfatal myocardial infarction, or nonfatal stroke)
REWIND
= Researching cardiovascular Events with a Weekly INcretin in
Diabetes
T2DM
= type 2 diabetes mellitus