Immunomodulatory Effects of SGLT2 Inhibitors—Targeting Inflammation and Oxidative Stress in Aging

Ema Schönberger, Vjera Mihaljević, Kristina Steiner, Sandra Šarić, Tomislav Kurevija, Ljiljana Trtica Majnarić, Ines Bilić Ćurčić () and Silvija Canecki-Varžić
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Ema Schönberger: Department of Endocrinology, University Hospital Osijek, 31000 Osijek, Croatia
Vjera Mihaljević: Department of Pharmacology and Biochemistry, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia
Kristina Steiner: Department of Endocrinology, University Hospital Osijek, 31000 Osijek, Croatia
Sandra Šarić: Department for Cardiovascular Disease, University Hospital Osijek, 31000 Osijek, Croatia
Tomislav Kurevija: Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia
Ljiljana Trtica Majnarić: Department of Family Medicine, Faculty of Medicine, Josip Juraj Strossmayer University of Osijek, Josipa Huttlera 4, 31000 Osijek, Croatia
Ines Bilić Ćurčić: Department of Endocrinology, University Hospital Osijek, 31000 Osijek, Croatia
Silvija Canecki-Varžić: Department of Endocrinology, University Hospital Osijek, 31000 Osijek, Croatia

IJERPH, 2023, vol. 20, issue 17, 1-19

Abstract: Given that the increase in the aging population has grown into one of the largest public health issues, inflammation and oxidative stress, which are closely associated with the aging process, became a focus of recent research. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, a group of drugs initially developed as oral antidiabetics, have shown many beneficial effects over time, including improvement in renal function and cardioprotective effects. It has been shown that SGLT2 inhibitors, as a drug class, have an immunomodulatory and antioxidative effect, affecting endothelial function as well as metabolic parameters. Therefore, it is not surprising that various studies have investigated the potential mechanisms of action of SGLT2 inhibitors in age-related diseases. The proposed mechanisms by which SGLT2 inhibitors can achieve their anti-inflammatory effects include influence on AMPK/SIRT1/PGC-1α signaling, various cytokines, and the NLRP3 inflammasome. The antioxidative effect is related to their action on mitochondria and their influence on the signaling pathways of transforming growth factor β and nuclear erythroid 2-related factor 2/antioxidant response element. Also, SGLT2 inhibitors achieve their anti-inflammatory and antioxidative effects by affecting metabolic parameters, such as uric acid reduction, stimulation of ketogenesis, reduction of body weight, lipolysis, and epicardial fat tissue. Finally, SGLT2 inhibitors display anti-atherosclerotic effects that modulate inflammatory reactions, potentially resulting in improvement in endothelial function. This narrative review offers a complete and comprehensive overview of the possible pathophysiologic mechanisms of the SGLT2 inhibitors involved in the aging process and development of age-related disease. However, in order to use SGLT2 inhibitor drugs as an anti-aging therapy, further basic and clinical research is needed to elucidate the potential effects and complex mechanisms they have on inflammation processes.

Keywords: inflammation; oxidative stress; SGLT2 inhibitors; aging; signaling pathways (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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