Exploration of regional heterogeneity in trials assessing the efficacy of recent non-insulin glucose lowering drugs on cardiovascular outcomes

Diabetes is a major health issue, affecting almost 425 million people worldwide. Type 2 diabetes accounts for about 90% of all diagnosed cases of diabetes in adults. Cardiovascular events, such as myocardial infarction or stroke, are considered as the foremost cause of death in patients with type 2 diabetes. Several glucose lowering drugs have shown efficacy to control chronic hyperglycemia. Recently marketed drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1Ra) and sodium glucose linked transporter-2 inhibitor (SGLT-2i), have further shown efficacy to reduce cardiovascular events in type 2 diabetes. These results are derived from large, international clinical trials. In a preliminary analysis (8), we have shown that geographic variations might exist in these clinical trials, suggesting that benefit from these drugs might differ according to the region of the world. These differences, if they are confirmed, could be explained by different factors, such as genetic variations, differences in lifestyle and diet, or in background therapy.
The primary objective of this study is to assess whether efficacy of GLP-1 analogs and SGLT-2 inhibitors on cardiovascular events is homogenous across the different regions of the world, and if not, to find the factors explaining such variability.