Novel metabolic drugs for the management of type 2 diabetes

Abstract

The prevalence of type 2 diabetes is dramatically increasing both in the UK and globally. This has led to a greater focus on the development of new and effective treatments and numerous agents are currently being investigated that target the metabolic processes underlying the disease. In this article, we focus on drugs that may particularly benefit the cardiometabolic, insulin resistance dysfunctions of type 2 diabetes. The peroxisome proliferator-activated receptor (PPAR)-(gamma) is the target for the currently available anti-diabetes drugs, rosiglitazone and pioglitazone. Agents that combine the potentially beneficial effects of activating both PPAR-(alpha) and PPAR-(gamma) are also being developed and are known as the glitazars. Two of these agents, muraglitazar and tesaglitazar, are showing promise in Phase III trials. Activation of PPAR-(gamma) can be associated with weight gain and oedema, however, which may impact on patient compliance. The novel insulin sensitiser, metaglidasen, exhibits the insulin sensitising qualities of the thiazolidinediones, but does not appear to have the associated tolerability issues. Obesity, especially abdominal obesity, is a well known risk factor and is closely associated with the development of type 2 diabetes. The new cannabinoid receptor 1 (CB1) blocker, rimonabant, has been shown to have beneficial effects on abdominal obesity, dyslipidaemia and hyperglycaemia and so might be an effective treatment for abdominally obese patients with type 2 diabetes. The increasing impact of type 2 diabetes as a major health care concern necessitates that efforts are continued in developing agents that can provide increasing benefit for the effective management of this disease. Copyright (copyright) 2006 John Wiley & Sons, Ltd.