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Cardiovascular safety for once-weekly dulaglutide in type 2 diabetes: a pre-specified meta-analysis of prospectively adjudicated cardiovascular events.
- Source :
-
Cardiovascular diabetology [Cardiovasc Diabetol] 2016 Feb 24; Vol. 15, pp. 38. Date of Electronic Publication: 2016 Feb 24. - Publication Year :
- 2016
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Abstract
- Background: Patients with type 2 diabetes (T2D) have a substantial increased risk for cardiovascular (CV) disease and associated mortality than those without diabetes. Dulaglutide is a once-weekly glucagon-like peptide-1 receptor agonist that is approved for treatment of T2D.<br />Methods: This meta-analysis evaluates the CV risk in patients with T2D treated with dulaglutide in 9 randomized safety and efficacy trials. Mean (median) treatment duration was 333 (358) days. Reported CV events were independently adjudicated by a treatment-blinded clinical endpoint committee. The primary measure was a 4-component major adverse CV event (4-component MACE) composite endpoint of death due to CV causes, nonfatal myocardial infarction (MI), nonfatal stroke, or hospitalization for unstable angina. Additional pre-specified endpoints included adjudicated coronary revascularizations, hospitalization for heart failure, and all-cause mortality. A Cox proportional hazards regression model (stratified by study) was used to estimate the hazard ratio (HR) and confidence interval (CI). Tests of treatment effects for the primary endpoint were conducted at a 2-sided alpha level of 0.0198 and a corresponding 98.02 % CI was calculated. Statistical heterogeneity between the strata (studies) was tested by including in the Cox model an interaction term between treatment and strata.<br />Results: The analysis included 6010 randomized patients [dulaglutide: 3885; comparator therapy (active or placebo): 2125]; cumulative exposure to dulaglutide or comparator therapy was 3941 and 2223 patient-years, respectively. The demographic and baseline CV disease characteristics were similar across groups. Twenty-six (0.67 %) patients in the dulaglutide group versus 25 (1.18 %) in the comparator group experienced a primary 4-component MACE (HR 0.57; adjusted 98.02 % CI 0.30, 1.10). Results for the 3-component MACE (composite endpoint of death due to CV causes, nonfatal MI or stroke), 6-component MACE (composite endpoint of death due to CV causes, nonfatal MI or stroke, hospitalization for unstable angina or heart failure, or coronary revascularizations) and all-cause mortality were consistent with the primary analysis (HR < 1.0 for all).<br />Conclusions: These results suggest that dulaglutide does not increase the risk of major CV events in T2D patients. The ongoing CV outcomes study, Researching CV Events with a Weekly Incretin in Diabetes (REWIND), will further assess CV safety of dulaglutide.
- Subjects :
- Aged
Biomarkers blood
Blood Glucose drug effects
Blood Glucose metabolism
Cardiovascular Diseases diagnosis
Cardiovascular Diseases mortality
Clinical Trials, Phase III as Topic
Diabetes Mellitus, Type 2 blood
Diabetes Mellitus, Type 2 complications
Diabetes Mellitus, Type 2 diagnosis
Diabetes Mellitus, Type 2 mortality
Drug Administration Schedule
Female
Glucagon-Like Peptide-1 Receptor agonists
Glucagon-Like Peptide-1 Receptor metabolism
Glucagon-Like Peptides administration & dosage
Glucagon-Like Peptides adverse effects
Humans
Hypoglycemic Agents adverse effects
Immunoglobulin Fc Fragments adverse effects
Kaplan-Meier Estimate
Male
Middle Aged
Proportional Hazards Models
Prospective Studies
Protective Factors
Randomized Controlled Trials as Topic
Recombinant Fusion Proteins adverse effects
Risk Assessment
Risk Factors
Treatment Outcome
Cardiovascular Diseases etiology
Diabetes Mellitus, Type 2 drug therapy
Glucagon-Like Peptides analogs & derivatives
Hypoglycemic Agents administration & dosage
Immunoglobulin Fc Fragments administration & dosage
Recombinant Fusion Proteins administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1475-2840
- Volume :
- 15
- Database :
- MEDLINE
- Journal :
- Cardiovascular diabetology
- Publication Type :
- Academic Journal
- Accession number :
- 26912057
- Full Text :
- https://doi.org/10.1186/s12933-016-0355-z