Trulicity ® (dulaglutid) injektion

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Trulicity® (dulaglutid): Kardiovaskulär metaanalys

En metaanalys som utvärderade dulaglutidebehandling visade att det inte fanns någon ökning av en sammansatt endpoint av död (MACE-4) jämfört med kontrollbehandlinar.

Detailed Information

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
(n=3885)
n (%)

All Comparators
(n=2125)
n (%)

HRa
(adj. 98.02% CI)

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
(Est. 95% CI)

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.

References

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


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