Bonus Effects of Antidiabetic Drugs: Possible Beneficial Effects on Endothelial Dysfunction, Vascular Inflammation and Atherosclerosis

• Published in: Basic & clinical pharmacology & toxicology Vol. 123; no. 5; pp. 523 - 538
• Main Authors: Pereira, Camila A., Carneiro, Fernando S., Matsumoto, Takayuki, Tostes, Rita C.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.11.2018
• Subjects: Arteriosclerosis; Atherosclerosis; Cardiovascular diseases; Cardiovascular Diseases - prevention & control; Complications; Cytokines; Diabetes; Diabetes mellitus; Diabetic Angiopathies - drug therapy; Diabetic Angiopathies - immunology; Diabetic Angiopathies - metabolism; Drug development; Drugs; Fibrosis; Health risks; Heart diseases; Homeostasis; Humans; Hyperglycemia; Hyperlipidemia; Hypoglycemic Agents - pharmacology; Immune system; Immunosuppressive agents; Infiltration; Inflammation; Inflammation - drug therapy; Life expectancy; Life span; Matrix metalloproteinases; Metabolic disorders; Oxidative stress; Oxidative Stress - drug effects; Stretching; Treatment Outcome; Vascular Resistance - drug effects
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.13054

Diabetes currently affects more than 400 million people worldwide. This metabolic disorder causes various micro‐ and macrovascular complications that accelerate atherosclerosis and yet trigger other cardiovascular diseases. The characteristic frame of hyperglycaemia, hyperinsulinaemia and hyperlipidaemia in diabetes increases several inflammatory mediators leading to endothelial dysfunction and pro‐atherosclerotic processes. This MiniReview summarizes evidence that antidiabetic drugs have effects beyond lowering glycaemic levels. In experimental studies, antidiabetic drugs reduce the vascular production and release of pro‐inflammatory cytokines, the recruitment, infiltration and activation of immune cells and pro‐inflammatory mediators, thus decreasing vascular inflammatory responses; they also re‐establish vascular redox homeostasis by reducing oxidative stress and balancing the release of vasoconstrictor and vasodilator factors, hence contributing to the improvement of endothelial function. These effects are associated with a reduction in vascular remodelling due to decreased matrix metalloproteinases expression/activity, reduced inflammatory processes and vascular wall fibrosis. In clinical studies, antidiabetic drugs also reduce the production and release of pro‐inflammatory, pro‐atherosclerotic and pro‐oxidative mediators and improve flow‐mediated dilatation, indicating beneficial effects on endothelial function. These bonus effects of antidiabetic drugs may delay and/or reduce the installation and development of the atherosclerotic disease, decrease cardiovascular risk and possibly impact mortality risk, life expectancy and quality.