An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis

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.

Automated summary

Metabolic diseases, especially diabetes mellitus (DM), are significant global public health concerns. Standard-of-care therapies for DM have not effectively reduced cardiovascular disease (CVD), which remains the leading cause of death among diabetic patients. Recent clinical trials have shown that SGLT2 inhibitors and GLP-1 receptor agonists can improve cardiorenal outcomes in type 2 DM patients, indicating a paradigm shift in DM management to focus on cardiovascular outcomes as well as glycemic control. The mechanisms behind the beneficial effects of these drugs, such as inflammation, oxidative stress, and fibrosis, are still not fully understood.