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Trulicity ® (dulaglutid) injektion
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A meta-analysis that included four phase 2 and five phase 3 clinical studies evaluated the risk of MACE with once-weekly dulaglutide treatment compared with placebo or active comparator in patients with T2DM.1
Design
A total of 6010 patients were evaluated including
3885 dulaglutide-treated patients, and
2125 placebo or active comparator-treated patients.1
History of CV disease was reported amongst 9% of patients.2
The investigators defined CV disease as having a history of at least one of the following:
MI
unstable angina
coronary revascularization
stroke or TIA
peripheral vascular disease
heart failure
lower extremity arterial revascularization,
carotid revascularization, or
coronary artery disease.2
The duration of study was
12 to 26 weeks for phase 2 studies, and
52 to 104 weeks for phase 3 studies.1
The dose of dulaglutide was
0.1 to 3 mg for phase 2 studies and the dose-finding portion of the AWARD-5 study, and
0.75 mg or 1.5 mg for the phase 3 studies.1
Primary Endpoint
The primary endpoint was a composite endpoint of MACE-4, which includes death due to CV causes, nonfatal MI, nonfatal stroke, or hospitalization for unstable angina.1
Results
A total of 51 patients experienced the primary endpoint, including
26 dulaglutide-treated patients (0.67%), and
25 placebo or active comparator-treated patients (1.18%) (HR=0.57; adjusted 98.02% CI: 0.30, 1.10; p=.046)(Table 1).1
Treatment with once-weekly dulaglutide for up to 104 weeks did not increase the risk of MACE-4.1
Table 1. Time-to-event Analysis of the Primary and Other CV Endpoints for all Randomized Patients 1
Endpoint |
DU |
All
Comparators |
HRa |
P Valuea |
Primary endpoint: MACE-4 |
26 (0.67) |
25 (1.18) |
0.57 (0.30, 1.10) |
.046 |
Individual Components of MACE-4 |
||||
Death from CV causesb |
3 (0.08) |
5 (0.24) |
0.35 (0.07, 1.87) |
.119 |
Nonfatal MI |
9 (0.23) |
14 (0.66) |
0.35 (0.13, 0.95) |
.014 |
Nonfatal stroke |
12 (0.31) |
4 (0.19) |
1.61 (0.42, 6.20) |
.411 |
Hospitalization for unstable angina |
3 (0.08) |
6 (0.28) |
0.28 (0.05, 1.46) |
.054 |
|
HRc |
P Valuec |
||
MACE-3d |
23 (0.59) |
21 (0.99) |
0.60 (0.33, 1.08) |
.090 |
Heart failure requiring hospitalization |
7 (0.18) |
2 (0.09) |
2.02 (0.41, 9.88) |
.378 |
Coronary revascularization |
13 (0.33) |
16 (0.75) |
0.44 (0.21, 0.92) |
.029 |
Percutaneous coronary intervention |
11 (0.28) |
14 (0.66) |
0.43 (0.19, 0.95) |
.036 |
Coronary artery bypass grafting |
2 (0.05) |
2 (0.09) |
-- |
-- |
All-cause mortality |
7 (0.18) |
8 (0.38) |
0.50 (0.18, 1.38) |
.181 |
Abbreviations: adj = adjusted; AWARD = Assessment of Weekly AdministRation of LY2189265 (dulaglutide) in Diabetes; CV = cardiovascular; DU = dulaglutide; Est = estimated; HR = hazard ratio; MACE = major adverse cardiovascular events; MACE‑3 = 3-component MACE; MACE-4 = 4-component MACE; MI = myocardial infarction.
a Calculated from a stratified Cox Proportional Hazards regression (response = treatment; strata = studies); phase 2 studies formed 1 stratum, AWARD-3 and AWARD-5 formed 1 stratum. For primary endpoint and each component of the composite primary endpoint: 2-sided p value compared to an alpha level of 0.0198 for test of superiority.
b Death from CV causes was defined as death from an acute MI, sudden cardiac death, death from heart failure, death from a stroke, and death from other CV causes.
c Calculated from a stratified Cox Proportional Hazards regression (response = treatment; strata = studies); phase 2 studies formed 1 stratum, AWARD-3 and AWARD-5 formed 1 stratum. When total number of outcomes was less than 10, survival analysis was not performed. When total number of outcomes was at least 5 and less than 10, Mantel-Haenszel odds ratio and p value by Cochran-Mantel-Haenszel test were reported. When total number of outcomes was less than 5, ratio and p value were not reported.
d Composite endpoint of death from CV causes, nonfatal MI, or nonfatal stroke.
1. Ferdinand KC, Botros FT, Atisso CM, Sager PT. Cardiovascular safety for once-weekly dulaglutide in type 2 diabetes: a pre-specified meta-analysis of prospectively adjudicated cardiovascular events. Cardiovasc Diabetol. 2016;15:38. https://doi.org/10.1186/s12933-016-0355-z
2. Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Glossary
AWARD = Assessment of Weekly AdministRation of LY2189265 in Diabetes
CV = cardiovascular
FDA = Food and Drug Administration
HR = hazard ratio
MACE = major adverse cardiovascular event
MI = myocardial infarction
T2DM = type 2 diabetes mellitus
TIA = transient ischemic attack
Datum fӧr senaste ӧversyn 2019 M05 22