Abstract
Type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD) are not merely coexisting epidemics but co-evolving manifestations of a shared cardiometabolic continuum. Despite advances in glycemic, lipid, and blood pressure control, residual cardiovascular risk remains high, underscoring the limitations of siloed approaches. In this perspective, we argue for reframing T2D and CVD as interconnected conditions driven by inflammation, adipose tissue dysfunction, and organ crosstalk. Beyond metformin, which remains foundational, several glucose-lowering drug classes are now evaluated not only for glycemic control but also for their cardiovascular and renal impact. Landmark trials and recent meta-analyses confirm that sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists improve cardiorenal outcomes. More recently, tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, has shown unprecedented efficacy in weight and glucose management, with potential to further transform cardiometabolic risk reduction. Yet enthusiasm for these therapies must be tempered by heterogeneity of response, treatment costs, and inequitable access. Integrated care models, supported by multidisciplinary teams, digital health tools, and value-based reimbursement, are essential to close the gap between trial efficacy and real-world outcomes. Attention to sex, age, ethnicity, and comorbidity profiles is critical to ensure equity, as is the adaptation of strategies to low- and middle-income countries where the burden of cardiometabolic disease is rapidly rising. Ultimately, advancing cardiometabolic medicine requires not only novel therapies but also a unifying framework that integrates biology, behavior, economics, and health systems to deliver the right treatment to the right patient at the right time.
Authors
Caturano, Alfredo; Morciano, Cassandra; Zielińska, Katarzyna; Russo, Vincenzo; Perrone, Marco Alfonso; Berra, Cesare Celeste; Conte, Caterina