Antifibrotic effects of sodium-glucose cotransporter-2 inhibitors: A comprehensive review

Abstract

Background and aims: Scar tissue accumulation in organs is the underlying cause of many fibrotic diseases. Due to the extensive array of organs affected, the long-term nature of fibrotic processes and the large number of people who suffer from the negative impact of these diseases, they constitute a serious health problem for modern medicine and a huge economic burden on society. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a relatively new class of anti-diabetic pharmaceuticals that offer additional benefits over and above their glucose-lowering properties; these medications modulate a variety of diseases, including fibrosis. Herein, we have collated and analyzed all available research on SGLT2is and their effects on organ fibrosis, together with providing a proposed explanation as to the underlying mechanisms.

Methods: PubMed, ScienceDirect, Google Scholar and Scopus were searched spanning the period from 2012 until April 2023 to find relevant articles describing the antifibrotic effects of SGLT2is.

Results: The majority of reports have shown that SGLT2is are protective against lung, liver, heart and kidney fibrosis as well as arterial stiffness. According to the results of clinical trials and animal studies, many SGLT2 inhibitors are promising candidates for the treatment of fibrosis. Recent studies have demonstrated that SGLT2is affect an array of cellular processes, including hypoxia, inflammation, oxidative stress, the renin-angiotensin system and metabolic activities, all of which have been linked to fibrosis.

Conclusion: Extensive evidence indicates that SGLT2is are promising treatments for fibrosis, demonstrating protective effects in various organs and influencing key cellular processes linked to fibrosis.

Keywords: Antifibrotic; Heart; Kidney; Liver; Lung; SGLT2 inhibitors.