Empagliflozin reduced long-term HbA1c variability and cardiovascular death: insights from the EMPA-REG OUTCOME trial.
Cardiovasc Diabetol
; 19(1): 176, 2020 10 13.
Article
in En
| MEDLINE
| ID: mdl-33050931
ABSTRACT
BACKGROUND:
Glucose variability has been associated with cardiovascular outcomes in type 2 diabetes, however, the interplay between glucose variability, empagliflozin and cardiovascular death has not been explored. In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of cardiovascular death by 38%. We explore post-hoc the association between HbA1c variability and cardiovascular death, and the potential mediating effects of HbA1c variability on empagliflozin's cardiovascular death reductions.METHODS:
In total, 7,020 patients with type 2 diabetes and established cardiovascular disease received placebo, empagliflozin 10 mg or 25 mg. We defined within-patient HbA1c variability as standard deviation, coefficient of variation and range of HbA1c measurements (%) post-baseline. First, we compared HbA1c variability until week 28 and 52 by Wilcoxon tests. We explored the association between cardiovascular death and HbA1c variability in placebo and pooled empagliflozin arms separately with landmark analyses at week 28 and 52, and additionally with HbA1c variability as a time-dependent co-variate. We used Cox regression models adjusted for baseline risk factors including changes in HbA1c from baseline to week 12, and the interaction term HbA1c variability* treatment.RESULTS:
HbA1c variability was lower with empagliflozin compared to placebo. In all Cox analyses, high HbA1c variability increased the risk for cardiovascular death in both treatment arms with no interaction with treatment e.g. an increase in HbA1c variability of one unit for the standard deviation at week 28 was associated with a subsequent increased risk of CV death with HRs of 1.97 (95% CI 1.36, 2.84) and 1.53 (1.01, 2.31) in the placebo and empagliflozin groups, separately, interaction p-value 0.3615.CONCLUSIONS:
HbA1c variability was reduced by empagliflozin and high values of HbA1c variability were associated with an increased risk of cardiovascular death. Empagliflozin's reduction in cardiovascular death did not appear to be mediated by reductions in HbA1c variability. ClinicalTrials.gov number, NCT01131676.Key words
Full text:
1
Database:
MEDLINE
Main subject:
Benzhydryl Compounds
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Blood Glucose
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Glycated Hemoglobin
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Cardiovascular Diseases
/
Diabetes Mellitus, Type 2
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Sodium-Glucose Transporter 2 Inhibitors
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Glycemic Control
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Glucosides
Type of study:
Clinical_trials
/
Diagnostic_studies
/
Etiology_studies
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Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Cardiovasc Diabetol
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
/
ENDOCRINOLOGIA
Year:
2020
Type:
Article
Affiliation country:
Italy