The Timeline of the Association Between Diabetes and Cardiovascular Diseases: A Narrative Review.

Diabetes and cardiovascular diseases (CVDs) are two strongly associated conditions that mutually influence each other. This review aims to follow the historical timeline of their association by highlighting the changing paradigm in CV risk management and treatment strategies in type 2 diabetes (T2D). While the discovery of insulin was a breakthrough in reducing life-threatening complications like diabetic ketoacidosis, patients with diabetes still faced a poor prognosis in terms of macrovascular outcomes, especially CVDs. Initial efforts in improving outcomes by tightly controlling glycemia proved insufficient, highlighting the complex relationship between the two diseases. After decades of focusing solely on glucose-lowering strategies, rosiglitazone, a promising new drug was developed, ultimately raising the flag about the potential higher risk of CV complications like myocardial infarction associated with its use. This turning point shifted the focus towards CV safety of novel glucose-lowering drugs, mandating for the development of cardiovascular outcome trials. Several drug classes, like sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), exceeded expectations by not only providing safety but also benefits in patients with T2D and CVDs and becoming the new standard of care in T2D management. The historical evidence linking T2D and CVDs has shaped regulatory requirements for cardiovascular outcome trials, guideline recommendations, and current therapeutic strategies. These insights highlight the importance of early interventions and a multidisciplinary approach to optimize patient outcomes.