AUTHOR=Carvalho Luiz Sergio Fernandes de , Nogueira Ana Claudia Cavalcante , Bonilha Isabella , Luchiari Beatriz , Benchimol Alexander , Couri Carlos Eduardo Barra , Borges Jairo Lins , Barreto Joaquim , Sposito Andrei C. 

TITLE=Glucose-Lowering and the Risk of Cardiovascular Events With Antidiabetic Therapies: A Systematic Review and Additive-Effects Network Meta-Analysis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.876795

DOI=10.3389/fcvm.2022.876795

ISSN=2297-055X

ABSTRACT=<sec><title>Aim</title><p>To assess the impact of the HbA1c levels achieved with antidiabetic therapies (ADTs) on the risk of MACE.</p></sec><sec><title>Methods</title><p>A systematic search was performed in PubMed, Cochrane, and <ext-link ext-link-type="uri" xlink:href="https://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials. gov</ext-link> for RCTs published up to March 2022 reporting the occurrence of MACE and all-cause mortality in individuals with T2DM treated with all marketed ADTs, including a sample size ≥100 individuals in each study arm and follow-up ≥24 weeks. A systematic review and additive-effects network meta-analysis with random effects and a multivariate meta-regression were utilized to assess the impact of achieved HbA1c on incident MACE.</p></sec><sec><title>Results</title><p>We included 126 RCTs with 143 treatment arms, 270,874 individuals, and 740,295 individuals-years who were randomized to an active treatment vs. control group. Among all ADTs, only therapy with SGLT2i, GLP1-RA, or pioglitazone similarly reduced the risk of MACE compared to placebo. The achievement of HbA1c ≤ 7.0% in RCTs with the 3 drug classes in the active arm was associated with an adjusted HR of 0.91 (95% CI 0.80, 0.97; <italic>p</italic> = 0.017) compared with HbA1c&gt;7.0%, without affecting all-cause mortality. These results, however, were not maintained among all ADTs.</p></sec><sec><title>Conclusions</title><p>Achieving lower glucose levels with SGLT2i, GLP1-RA, or pioglitazone is linearly associated with a reduced risk of MACEs, without affecting all-cause mortality.</p></sec><sec><title>Systematic Review Registration</title><p><ext-link ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213127" xmlns:xlink="http://www.w3.org/1999/xlink">www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213127</ext-link>, identifier: CRD42020213127.</p></sec>