On The Horizon: New Oral Therapies for Type 2 Diabetes Mellitus

The first documented case of diabetes mellitus occurred earlier than 4000 BC. Since then, many of the brightest minds in medicine have dedicated their time and effort toward developing treatments that can reverse the course of this deadly disease. As our understanding of the pathogenesis of diabetes increases, so does the availability of treatment options. The fight against diabetes once only had metformin and sulfonylureas as the cornerstone of oral treatment, but now, multiple classes have been added to this armamentarium including thiazolidenediones (TZDs) and dipeptidyl peptidase IV (DDP IV) inhibitors. These therapies provide reasonable durable glycemic control but are unable to arrest the natural progression of diabetes or the eventual need for insulin. By utilizing our growing knowledge on the pathogenesis of diabetes, a number of new therapeutic agents are in development to overcome the shortcomings of current therapies. Promising options on the horizon include sodium-coupled glucose cotransport 2 (SGLT2) inhibitors, Ranolazine, Salicylates, second generation Peroxisome proliferator ac-tivator receptor agonists (PPARs), and 11-beta hydroxysteroid dehydrogenase type 1 inhibitors (11-beta HSD1 inhibitors). Various molecules, including some enzymes, are also in development particularly to address beta cell preservation and its sensitivity to glucose, while minimizing hypoglycemia. Most of these new classes of drugs consist of daily administration, simplifying the regimen for patients and likely increasing medication compliance. This article reviews the new agents that are advancing through clinical trials, their mechanism of actions, glucose lowering effect and possible side effects and limitations.