Shifting Paradigms in the Medical Management of Type 2 Diabetes: Reflections on Recent Cardiovascular Outcome Trials

An important challenge in the management of patients with type 2 diabetes is cardiovascular disease (CVD) prevention. While it is well established that intensive glycemic control prevents the onset and slows the progression of certain microvascular complications, such a strategy utilized in multiple clinical trials over the past few decades has failed to show a similar benefit with regard to cardiovascular events, including mortality. Despite this, a major hope has been the discovery of glucose-lowering medications that simultaneously improve cardiovascular outcomes. Over the past year and a half, four randomized clinical trials (involving empagliflozin, pioglitazone, liraglutide, and semaglutide) have reported important benefits in preventing adverse cardiovascular outcomes in patients with or at risk for type 2 diabetes and established CVD. On the basis of these landmark trials, we propose that a paradigm shift in the management of patients with type 2 diabetes, specifically in those with prior macrovascular disease. A transition from current algorithms based primarily on hemoglobin A1c values to a more comprehensive strategy additionally focused on CVD prevention seems warranted.