Search

The incidence of cardiovascular disease is substantially increased in patients with type 1 diabetes compared to the general population. Robust evidence from the randomized Diabetes Control and Complications Trial (DCCT) and the long-term epidemiologic surveillance of its participants suggest that tight glycemic control by means of intensive insulin treatment is efficacious both in primary and secondary prevention of cardiovascular disease. New antidiabetic agents with proven cardiorenal benefit in patients with type 2 diabetes, such as Glucagen-Like Polypeptide-1 Receptor Agonists (GLP-1RA) and Sodium-Glucose co-Transporter-2 Inhibitors (SGLT-2inh), have been tested as adjunctive to insulin treatment in a few clinical trials in patients with type 1 diabetes. Despite their favorable effect on risk factors for atherosclerotic disease, such as body weight and blood pressure, the lack of evidence for a direct effect on cardiovascular outcomes and an increased risk for serious adverse events, such as diabetic ketoacidosis, limit their use in patients with type 1 diabetes. New metrics of glycemia, alterations in diabetes classification and precision medicine may contribute in an individualized approach of cardiovascular risk prevention in patients with diabetes.

Metformin has been for many years the first-line pharmaceutic treatment for most patients with type 2 diabetes. However, new classes of antidiabetic agents with proven cardiorenal benefits beyond glycemic control challenge metformin’s predominance. The hypoglycemic effect of metformin is mediated in liver by inhibiting gluconeogenesis and improving insulin sensitivity and in intestines by reducing glucose absorption, increasing incretins and altering intestinal microbiome. After decades of use metformin has been proved to be one of the most potent, safe and cost-effective medications for the treatment of type 2 diabetes. Several other pleiotropic actions of metformin in inflammation pathways suggest a potential cardioprotective role. This hypothesis has been tested in a few randomized trials and in more observational studies and metanalyses with controversial results. Given the lack of robust evidence for the cardioprotective effect of metformin compared to the newer antidiabetic agents, current treatment algorithms are under scrutiny. Ongoing randomized clinical trials comparing metformin to placebo are expected to elucidate the effect of metformin on specific cardiovascular and renal outcomes.