Metabolic diseases, particularly diabetes mellitus (DM), are significant global public
health concerns. Despite the widespread use of standard-of-care therapies, cardiovascular
disease (CVD) remains the leading cause of death among diabetic patients. Early and
evidence-based interventions to reduce CVD are urgently needed. Large clinical trials
have recently shown that sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like
peptide-1 receptor agonists (GLP-1RA) ameliorate adverse cardiorenal outcomes in patients
with type 2 DM. These quite unexpected positive results represent a paradigm shift
in type 2 DM management, from the sole importance of glycemic control to the simultaneous
improvement of cardiovascular outcomes. Moreover, SGLT2i is also found to be cardio-
and nephroprotective in non-diabetic patients. Several mechanisms, which may be potentially
independent or at least separate from the reduction in blood glucose levels, have
already been identified behind the beneficial effect of these drugs. However, there
is still much to be understood regarding the exact pathomechanisms. This review provides
an overview of the current literature and sheds light on the modes of action of novel
antidiabetic drugs, focusing on inflammation, oxidative stress, and fibrosis.
