TGR5 agonists for diabetes treatment: a patent review and clinical advancements (2012-present).

Introduction: A cell surface bile acid receptor TGR5 is expressed in various tissues, including the liver, kidney, intestine, and adrenal glands, causing its effect in each tissue to differ. A major role for TGR5 is to maintain blood sugar levels and increase in energy expenditure. These benefits make it a potential candidate for the treatment of type 2 diabetes, obesity, and other metabolic diseases.

Area Covered: This paper highlights recent advances in the development of potent steroidal and non-steroidal TGR5 agonists and the peer-reviewed scientific articles that have led to understanding the structure-activity relationship for TGR5 agonists (2012-2020). The review also discusses the clinical progress made by some TGR5 agonists over the past eight years.

Expert Opinion: In preclinical studies, TGR5 has been found to play a crucial role in GLP-1 secretion and has shown promise for weight loss, anti-diabetic outcomes etc. Semi synthetic and synthetic derivatives can be considered a potential avenue for discovering novel TGR5 agonists. Currently, few TGR5 agonists have reached the clinical trial stage, and, likely, soon novel TGR5 modulator will be discovered with fewer adverse effects. In silico studies can also be performed with various heterocyclic scaffolds to discover selective and safe TGR5 agonists.