Frontiers in Cardiovascular Medicine (Apr 2022)
Glucose-Lowering and the Risk of Cardiovascular Events With Antidiabetic Therapies: A Systematic Review and Additive-Effects Network Meta-Analysis
Abstract
AimTo assess the impact of the HbA1c levels achieved with antidiabetic therapies (ADTs) on the risk of MACE.MethodsA systematic search was performed in PubMed, Cochrane, and ClinicalTrials. gov 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.ResultsWe 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; p = 0.017) compared with HbA1c>7.0%, without affecting all-cause mortality. These results, however, were not maintained among all ADTs.ConclusionsAchieving lower glucose levels with SGLT2i, GLP1-RA, or pioglitazone is linearly associated with a reduced risk of MACEs, without affecting all-cause mortality.Systematic Review Registrationwww.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213127, identifier: CRD42020213127.
Keywords
