Detailed
Information
The
AWARD-5 study was an adaptive, multicenter, randomized, 104-week,
double-blind study that compared once-weekly dulaglutide 1.5 mg
and dulaglutide 0.75 mg treatments with once-daily sitagliptin 100 mg
and placebo in patients with T2DM inadequately controlled with
metformin.1,2
Treatment
with dulaglutide was associated with a significantly higher incidence
of GI TEAEs than treatment with sitagliptin (p<.05).1,2
Nausea,
diarrhea, and vomiting were the most commonly reported AEs with the
incidence highest after 2 weeks of treatment and decreased at the
following visits.1
Both
dulaglutide 1.5 mg and dulaglutide 0.75 mg treatment doses reported
more TEAEs than the sitagliptin treatment group due to greater
incidence of GI AEs (Table 1).1
A
similar incidence of serious AEs was reported across treatment groups
(Table 1).1
Table
1. Adverse Events From Baseline to 104 Weeks in Patients Treated With
Dulaglutide 1.5 mg, Dulaglutide 0.75 mg, or Sitagliptin 100
mg in the AWARD-5 Study 1,3
|
Variablea
|
DULA
1.5 mg
n=304
|
DULA
0.75 mg
n=302
|
SITA
100 mg
n=315
|
|
Treatment-emergent
adverse events ≥1
|
259
(85)
|
255
(84)
|
242
(77)
|
|
Treatment-emergent
GI adverse events
|
|
Nausea
|
53
(17)
|
44
(15)
|
21
(7)
|
|
Vomiting
|
41
(14)
|
25
(8)
|
11
(4)
|
|
Diarrhea
|
49
(16)
|
36
(12)
|
18
(6)
|
|
Abdominal
pain
|
21
(7)
|
13
(4)
|
11
(4)
|
|
Abdominal
distention
|
13
(4)
|
15
(5)
|
3
(1)
|
|
Dyspepsia
|
18
(6)
|
19
(6)
|
14
(4)
|
|
Pancreatic
enzymes, median (Q1,Q3) [U/I]
|
|
Lipase
|
6
(-1,14)
|
6
(-1,18)
|
3
(-2,9)
|
|
Total
amylase
|
6
(-1,15)
|
7
(-1,17)
|
3
(-3,12)
|
|
p-Amylase
|
4
(0,9)
|
4
(0,11)
|
2
(-1,7)
|
|
Pancreatitis
|
0
(0)
|
0
(0)
|
2
(0.6)
|
|
Serious
adverse events
|
36 (12)
|
23 (8)
|
32 (10)
|
|
Infections
and infestations
|
7 (2)
|
3 (1)
|
5 (2)
|
|
Cardiac
disorders
|
6 (2)
|
2 (1)
|
4 (1)
|
|
Neoplasms
|
5 (2)
|
3 (1)
|
5 (2)
|
|
Gastrointestinal
events
|
4 (1)
|
2 (1)
|
4 (1)
|
|
Renal/urinary
disorders
|
5 (2)
|
2 (1)
|
0 (0)
|
|
Death
|
1 (<1)
|
0
(0)
|
2
(1)
|
|
Injection
site reactions
|
4
(1.3)
|
3
(1.0)
|
3
(1.0)
|
|
Hypoglycemiab,
mean (SD)
|
|
Total
|
0.0
(0.2)
|
0.0
(0.5)
|
0.0
(0.3)
|
|
Documented
symptomatic
|
0.0
(0.1)
|
0.0
(0.5)
|
0.0
(0.3)
|
|
Discontinuation
resulting from adverse events
|
63
(21)
|
64
(21)
|
65
(21)
|
|
Vital
signs, LSM (SE)
|
|
Systolic
blood pressure, mmHg
|
-0.1
(0.8)
|
1.3
(0.8)
|
<0.1
(0.8)
|
|
Diastolic
blood pressure, mmHg
|
0.4
(0.5)
|
1.4
(0.5)
|
-0.4
(0.5)
|
|
Pulse
rate, beats/min
|
2.3
(0.5)
|
2.8
(0.5)
|
-0.8
(0.5)
|
Abbreviations:
AWARD = Assessment of Weekly AdministRation of LY2189265 in Diabetes;
DULA = dulagultide; GI = Gastrointestinal; LSM = least squares
mean; Q1 = first quartile; Q3 = third quartile; SITA =
Sitagliptin; U/l = units per liter.
a
Data presented as n (%) unless otherwise indicated.
b
<54 mg/dL cutoff, 1-year adjusted rate.
References
1.
Weinstock RS, Guerci B, Umpierrez G, et al. Safety and efficacy of
once-weekly dulaglutide versus sitagliptin after 2 years in
metformin-treated patients with type 2 diabetes (AWARD-5): a
randomized, phase III study. Diabetes Obes Metab.
2015;17(9):849-858. http://dx.doi.org/10.1111/dom.12479
2.
Nauck M, Weinstock RS, Umpierrez GE, et al. Efficacy and safety of
dulaglutide versus sitagliptin after 52 weeks in type 2 diabetes in a
randomized controlled trial (AWARD-5). Diabetes Care.
2014;37(8):2149-2158. http://dx.doi.org/10.2337/dc13-2761
3.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Glossary
AE =
adverse event
AWARD
= Assessment of Weekly AdministRation of LY2189265 in Diabetes
GI =
gastrointestinal
T2DM
= type 2 diabetes mellitus
TEAE
= treatment-emergent adverse event