[Incretin-based therapies and cardiovascular outcome: analyses, pooled analyses and meta-analyses]

The assessment of the effects on cardiovascular risk is necessary for all new drugs for diabetes, including glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. While waiting for the results of ongoing clinical trials specifically designed for cardiovascular outcomes, some analyses were performed on major cardiovascular events reported as severe adverse events in short- and medium-term trials with metabolic endpoints. Several pooled analyses of trials with individual molecules, based on patient-level data, showed a trend toward a reduction in the incidence of major cardiovascular events, which reached statistical significance in some cases. Meta-analyses of the same trials, combining all molecules of each class, showed that DPP-4 inhibitors are associated with a significant reduction of major cardiovascular events and mortality; in trials with GLP-1 receptor agonists, which are fewer because of the smaller number of available molecules, a similar trend is observed, reaching statistical significance only for major cardiovascular events in placebo-controlled trials. In conclusion, currently available data suggest that incretin-based therapies are probably associated with a relevant reduction of cardiovascular risk. These promising results need to be confirmed by ongoing large-scale trials.