Geographic Variation in Cardiovascular Disease Prevention by GLP-1 Receptor Agonists and SGLT2 Inhibitors: A Meta-Analysis

Based on cardiovascular outcome trials, the FDA has approved the indication to reduce the risk of cardiovascular events in patients with diabetes for GLP-1 receptor agonists and SGLT-2 inhibitors. We assess the effect of GLP-1 receptor agonists and SGLT-2 inhibitors on cardiovascular risk reduction according to geographic areas. We performed a systematic search of cardiovascular outcome trials in PubMed (MEDLINE) until September 2024. We included cardiovascular outcome trials with these medications that demonstrated a reduction in major cardiovascular events in patients with diabetes and provided geographic sub-analyses of these outcomes. The data was extracted from the study publications, including their supplementary material. A statistical meta-analysis was conducted to assess differences in cardiovascular risk reduction by region. The primary outcome was the regional variation in cardiovascular risk reduction, as measured by major cardiovascular events, associated with these medications. We found 5 studies with GLP-1 receptor agonists and 2 with SGLT-2 inhibitors in which a reduction in major cardiovascular events was recorded and related geographic sub-analysis was published. None of the studies demonstrated major cardiovascular events improvement in North America. Almost all the studies found higher hazard ratio for major cardiovascular events in North America as compared to whole study hazard ratio. We conclude that GLP-1 receptor agonists and SGLT-2 inhibitors do not decrease cardiovascular risk in diabetic patients in North America. Based on our results, the FDA should reconsider the registered indication of cardiovascular prevention in patients with diabetes mellitus for these medications.