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Meta-Analysis
. 2020 Aug;22(8):1397-1405.
doi: 10.1111/dom.14047. Epub 2020 May 7.

Relationship between improvement of glycaemic control and reduction of major cardiovascular events in 15 cardiovascular outcome trials: A meta-analysis with meta-regression

Dario Giugliano  1 , Giuseppe Bellastella  1 , Miriam Longo  1 , Lorenzo Scappaticcio  1 , Maria Ida Maiorino  2 , Paolo Chiodini  3 , Katherine Esposito  2
Affiliations
Meta-Analysis

Relationship between improvement of glycaemic control and reduction of major cardiovascular events in 15 cardiovascular outcome trials: A meta-analysis with meta-regression

Dario Giugliano et al. Diabetes Obes Metab. 2020 Aug.

Abstract

Aim: In order to disclose relations between reduction of haemoglobin A1c (HbA1c) levels and risk of major cardiovascular events (MACE), we performed a meta-analysis with metaregression of all cardiovascular outcome trials (CVOTs) so far published in patients with type 2 diabetes (T2D).

Materials and methods: An electronic search up to February 10, 2020 was conducted to determine eligible trials. Pooled summary estimates and 95% confidence intervals (CI) were calculated according to the random effects model using the Paule-Mandel method; restricted maximum likelihood estimators were used to estimate model parameters in the metaregression.

Results: The 15 CVOTs included evaluated 138,250 patients. In the pooled analysis, the risk of MACE was significantly reduced by 9% (hazard ratio, HR = 0.91, 0.87-0.95, P <0.001) as compared with placebo, with significant heterogeneity between trials (I2 = 44%, P = 0.060) There was a robust relation between the reduction in achieved HbA1c at the end of the trial and the HR reduction for MACE (beta = -0.3169, P = 0.029), explaining most (78%) of the between-study variance; this relation was totally driven by the risk reduction of non-fatal stroke only, which explained 100% of between-study variance, and apparently restricted to the class of glucagon-like peptide 1 receptor agonists (GLP-1RAs). There was no relation between the reduction in achieved HbA1c and the HR for heart failure (variance explained = 0%) or all-cause mortality (variance explained = 6%).

Conclusion: The blood glucose reduction observed in CVOTs may play some role in reducing the risk of non-fatal stroke, at least during treatment with GLP-1RAs, without affecting the other two components of MACE.

Keywords: cardiovascular outcome trials, glucagon-like peptide-1 receptor agonists, major cardiovascular events, meta-regression, non-fatal stroke, type 2 diabetes.

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References

REFERENCES

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