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Cardiovascular outcome trials and major cardiovascular events: does glucose matter? A systematic review with meta-analysis

  • D. GiuglianoEmail author
  • P. Chiodini
  • M. I. Maiorino
  • G. Bellastella
  • K. Esposito
Rapid Communication
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Abstract

Purpose

We did a meta-analysis with meta-regression to evaluate the relationship between hemoglobin A1c (A1C) reduction and the primary CV outcome of cardiovascular outcome trials (CVOTs).

Methods

We used a random effects meta-analysis of the 12 CVOTs to quantify the effect of A1C reduction on major cardiovascular events (MACE) risk by stratifying the difference in achieved A1C (drug vs placebo) in three strata: A1c < 0.3%, A1c ≥ 0.3% and < 0.5%, and A1c ≥ 0.5%.

Results

We found a relation between the reduction in achieved A1C and the hazard ratio reduction for MACE (P = 0.002), explaining almost all (94.1%) the between-study variances: lowering A1C by 0.5% conferred a significant HRR of 20% (95% CI 4–33%) for MACE.

Conclusions

Blood glucose reduction may play a more important role than previously thought in reducing the risk of MACE during treatment with the newer glucose-lowering drugs, including peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium–glucose co-transporter-2 inhibitors.

Keywords

CVOTs (cardiovascular outcome trials) Type 2 diabetes Major cardiovascular events Glycemic control 

Notes

Funding

No funding was specifically allocated for this study.

Compliance with ethical standards

Conflict of interest

D.G. received honoraria for speaking at meetings from Novartis, Sanofi-Aventis, Lilly, AstraZeneca, and NovoNordisk. M.I.M. received honoraria for speaking at meetings from Lilly and NovoNordisk. K.E. received honoraria for speaking at meetings from Novartis, Sanofi-Aventis, Lilly, AstraZeneca, Boehringer Ingelheim, and NovoNordisk. P.C. declares that he has no conflict of interest. G.B. declares that he has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Informed consent

For this type of study, informed consent is not required.

Supplementary material

40618_2019_1047_MOESM1_ESM.docx (20 kb)
Supplementary material 1 (DOCX 20 kb)

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Copyright information

© Italian Society of Endocrinology (SIE) 2019

Authors and Affiliations

  • D. Giugliano
    • 1
    Email author
  • P. Chiodini
    • 3
  • M. I. Maiorino
    • 2
  • G. Bellastella
    • 1
  • K. Esposito
    • 2
  1. 1.Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical SciencesUniversità della Campania Luigi VanvitelliNaplesItaly
  2. 2.Diabetes Unit, Department of Advanced Medical and Surgical SciencesUniversità della Campania Luigi VanvitelliNaplesItaly
  3. 3.Medical Statistics Unit, Department of Mental and Physical Health and Preventive MedicineUniversità della Campania Luigi VanvitelliNaplesItaly

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