Trulicity® (dulaglutid): Kardiovaskulär metaanalys

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

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