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

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.

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No funding was specifically allocated for this study.

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Correspondence to D. Giugliano.

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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.

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Giugliano, D., Chiodini, P., Maiorino, M.I. et al. Cardiovascular outcome trials and major cardiovascular events: does glucose matter? A systematic review with meta-analysis. J Endocrinol Invest 42, 1165–1169 (2019). https://doi.org/10.1007/s40618-019-01047-0

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Keywords

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