Advances in the treatment of metabolic diseases

Richard D. DiMarchi


This year represents a special one in the history of metabolic diseases and in particular their treatment with breakthrough medicines. A century ago, insulin emerged from the University of Toronto laboratories, a celebrated and miraculous discovery that demonstrated the power of medicine to sustain and enhance life. It also promoted the broader study of intermediary metabolism that has evolved into modern molecular metabolism. It is difficult to comprehend how a discovery of such importance and ultimate impact could occur with primitive technology relative to present day standards. It should be recalled, that its discovery and therapeutic application occurred three decades prior to the characterization of its primary structure. As we look back and celebrate this great accomplishment and subsequent progress in the field of metabolism over the last century, we should also focus on the future. With this as the primary purpose, we have assembled a Molecular Metabolism special issue to highlight several recent therapeutic successes, particularly those that hold great promise for transforming the treatment of diabetes, obesity, and related disease complications.

It is also nearly a half-century since the emergence of biotechnology, a technology that has transformed life sciences. At that point in time the treatment of diabetes consisted largely of animal sourced insulin and sulfonylureas, with metformin only accessible outside the United States. Blood glucose monitoring was just beginning to be introduced to guide patient management and assist in next generation drug discovery. Advances in diagnostic glucose measurement and digital information management facilitates continuous monitoring to provide 24/7 real-time assessment of glucose control. Insulin is now produced biosynthetically, and the structure has been optimized for greater precision, with lessened risk of hypoglycemia. Glucagon is finally available as a stable soluble formulation for ready injection or as a nasal administration to correct excessive blood glucose lowering. Metformin is an established first line therapy that is commonly complemented with one of two novel classes of oral drugs, DPP4-inhibitors, and SGLT2-inhibitors. The GLP-1 based analogs have provided breakthrough improvements in glucose management with reduction in cardiovascular risk. Recent clinical results have also demonstrated significant body weight lowering suggesting that we may be able to treat excess body weight as effectively as excess glucose and blood pressure.

The organization of this special issue begins with those chemical entities that have progressed to registered medicines, continues with those in clinical development and concludes with promising molecular targets that are the subject of pre-clinical studies. I am extremely grateful to the many authors that have provided their time to share their creativity as we collectively strive to advance the treatment of metabolic diseases. I hope you find this special issue of Molecular Metabolism to be of value in your personal research.