The management of type 2 diabetes predominantly focuses on reducing hemoglobin A1C (HbA1c). We examined the association between the magnitude of reduction in HbA1c and cardiovascular outcomes for new diabetes medications: sodium-glucose cotransporter-2 SGLT2 inhibitors, glucagon-like peptide-1 GLP1 agonists, and dipeptidyl peptidase-4 DPP4 inhibitors. We reviewed all published, placebo-controlled, randomized cardiovascular outcome trials. Meta-regression was performed to evaluate the association between HbA1c reduction (i.e., post-intervention HbA1c for active drug – pre-intervention HbA1c for active drug – post-intervention HbA1c for placebo – pre-intervention HbA1c for placebo) and the composite cardiovascular outcome (i.e., stroke, myocardial infarction, or cardiovascular death). We identified 14 cardiovascular outcome clinical trials, the median sample size was 9401, the median age was 64 years, the median time since diagnosis of diabetes was 12 years, and the median duration of trial follow-up was 120 weeks. Within individual medication classes, each additional 0.5% reduction in HbA1c in the active drug arm, relative to placebo, was associated with a lower incidence of cardiovascular events for GLP1 agonists (0.82, 0.68–0.98) but not for SGLT2 (0.97, 0.69–1.36) or DPP4 (1.03, 0.39–2.74) inhibitors. Our study provides further support that reducing the risk of cardiovascular events for adults with diabetes is partly explained by a reduction in HbA1c. •Among over 130,000 adults with diabetes, reduction in hemoglobin A1c was associated with a decrease in cardiovascular risk•The association between hemoglobin A1c reduction and decreased cardiovascular risk varies by medication class•For GLP-1 agonists, there is a strong correlation between hemoglobin A1c reduction and decreased cardiovascular risk•For SGLT2 inhibitors, there was no association between hemoglobin A1c reduction and cardiovascular risk