An updated perspective and pooled analysis of cardiovascular outcome trials of GLP-1 receptor agonists and SGLT-2 inhibitors.

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduce major cardiovascular (CV) events in patients with type 2 diabetes mellitus. In this review, we assessed the CV outcome trials of GLP-1 receptor agonists and SGLT-2 inhibitors in terms of their methodological properties and results, and also, using a meta-analytic approach, we calculated and interpreted the pooled analyses. A systematic PubMed search was conducted for CV outcome studies of GLP-1 receptor agonists and SGLT-2 inhibitors with the main outcome of three-point major adverse cardiovascular events (MACE), which is the composite of CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. We pooled the results of each outcome for each group of medications using a fixed effect model. Also, the results of two studies of SGLT-2 inhibitors conducted in patients with heart failure were discussed briefly. We found 12 eligible studies, 7 with GLP-1 agonists (n=56,004) and 5 with SGLT-2 inhibitors (n=46,969). All of the drugs analyzed were non-inferior, and some superior, to placebo in terms of three-point MACE. Pooled analyses demonstrated that GLP-1 receptor agonists, especially those having structural homology for human GLP-1 receptor, and SGLT-2 inhibitors reduced the risk of three-point MACE (by 12% and 10%, respectively), CV mortality (12% and 15%), total mortality (12% and 13%), and to a lesser extent, fatal or non-fatal MI (8% and 9%). While GLP-1 receptor agonists reduced the risk of ischemic stroke by 15%, SGLT-2 inhibitors decreased the risk of hospitalization for heart failure by 32%. GLP-1 agonists and SGLT-2 inhibitors reduced the risk of MACE in patients with type 2 diabetes with established CV disease or those with high risk for CV disease. Also, SGLT-2 inhibitors reduced the risk of hospitalization for heart failure independent of the diabetes status.