Recent recommendations regarding type 2 diabetes (T2D) patients’ treatments have focused on personalizing glycosylated haemoglobin (HbA_1c) targets. Because the relationship between HbA_1c and diabetes prognosis has been established from large prospective cohorts, it is valid to question the extrapolation from population-based risk reduction estimations to individual predictions. Our study aimed to investigate the relationship between HbA_1c reductions and clinical outcomes in randomized controlled trials (RCTs), using a meta-regression approach. Included were RCTs comparing intensive vs. standard glucose-lowering regimens for cardiovascular events and microvascular complications in T2D patients. Eight studies (33,396 patients) providing data for HbA_1c reductions were found. In our meta-regression, HbA_1c decreases were not significantly associated with reductions in our main study outcomes: total and cardiovascular mortality. They were also not associated with any of the secondary endpoints, including myocardial infarction, stroke and severe hypoglycaemia. Sensitivity analysis showed a significant correlation only between HbA_1c-lowering and severe hypoglycaemia (P=0.014). Meta-regression analysis could find no significant association between HbA_1c-lowering and a decrease in clinical outcomes, thereby questioning the use of HbA_1c as a surrogate outcome for T2D-related complications. Thus, RCTs vs. placebo are urgently required to evaluate the risk–benefit ratios of therapeutic strategies beyond HbA_1c control in T2D patients.