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Updated: Sep 23, 2025

A Zebrafish Model of Diabetes Mellitus and Metabolic Memory
Published on: February 28, 2013
Glucose-Lowering and the Risk of Cardiovascular Events With Antidiabetic Therapies: A Systematic Review and
Luiz Sergio Fernandes de Carvalho1,2,3, Ana Claudia Cavalcante Nogueira2,3, Isabella Bonilha2
1Laboratory of Data for Quality of Care and Outcomes Research, Clarity Healthcare Intelligence, Jundiaí, Brazil.
Aim:
To assess the impact of the HbA1c levels achieved with antidiabetic therapies (ADTs) on the risk of MACE.
Methods:
A 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.
Results:
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; p = 0.017) compared with HbA1c>7.0%, without affecting all-cause mortality. These results, however, were not maintained among all ADTs.
Conclusions:
Achieving 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 Registration:
www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020213127, identifier: CRD42020213127.
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