Dario Giugliano1, Giuseppe Bellastella1, Miriam Longo1, Lorenzo Scappaticcio1, Maria Ida Maiorino2, Paolo Chiodini3, Katherine Esposito2. 1. Division of Endocrinology and Metabolic Diseases, Department of Advanced Medical and Surgical Sciences, Università della Campania Luigi Vanvitelli, Naples, Italy. 2. Diabetes Unit, Department of Advanced Medical and Surgical Sciences, Università della Campania Luigi Vanvitelli, Naples, Italy. 3. Medical Statistics Unit, Università della Campania Luigi Vanvitelli, Naples, Italy.
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.
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.
Authors: Maria Ida Maiorino; Miriam Longo; Lorenzo Scappaticcio; Giuseppe Bellastella; Paolo Chiodini; Katherine Esposito; Dario Giugliano Journal: Cardiovasc Diabetol Date: 2021-10-18 Impact factor: 9.951
Authors: Miriam Longo; Lorenzo Scappaticcio; Paolo Cirillo; Antonietta Maio; Raffaela Carotenuto; Maria Ida Maiorino; Giuseppe Bellastella; Katherine Esposito Journal: Biomolecules Date: 2022-02-08