Current and emerging gluconeogenesis inhibitors for the treatment of Type 2 diabetes

In the last several decades, fueled by gene knockout and knockdown techniques, there has been substantial progress in detailing the pathways of gluconeogenesis. A host of molecules have been identified as potential targets for therapeutic intervention. A number of hormones, enzymes and transcription factors participate in gluconeogenesis. Many new agents have come into use to treat diabetes and several of these are in development to suppress gluconeogenesis.

Herein, the author reviews agents that have been discovered and/or are in development, which control excess gluconeogenesis. The author has used multiple sources including PubMed, the preprint servers MedRxIv, BioRxIv, Research Gate, as well as Google Search and the database of the U.S. Patent and Trademarks Office to find appropriate literature.

It is now clear that lipid metabolism and hepatic lipogenesis play a major role in gluconeogenesis and resistance to insulin. Future efforts will focus on the duality of gluconeogenesis and adipose tissue metabolism. The exploration of therapeutic RNA agents will accelerate. The balance of clinical benefit and adverse effects will determine the future of new gluconeogenesis inhibitors.