Management of type 2 diabetes in the obese patient: current concerns and emerging therapies

The aims of this review are (1) to examine the pathophysiologic relationship between type 2 diabetes and obesity, (2) to provide an overview of current and emerging treatments for type 2 diabetes and their effects on body weight.

A MEDLINE search was performed for literature published in the English language from 1966 to 2006. Abstracts and presentations from the American Diabetes Association Scientific Sessions (2002-2006) and the European Association for the Study of Diabetes Annual Meetings (1998-2006) were also searched for relevant studies. Preclinical and clinical data were selected for inclusion based on novelty and pertinence to treatment of the obese patient.

Recent guidelines suggest that all patients with type 2 diabetes should initially receive metformin as well as lifestyle intervention, followed by rapid administration of other oral anti-diabetic agents or insulin if glycemic goals are not met or maintained. Many oral anti-diabetic drugs, and insulin, are associated with weight gain. New agents with anti-diabetic activity that may be advantageous in obese patients with type 2 diabetes have recently become available. These include injectable incretin mimetics, which reduce blood glucose while reducing body weight but commonly cause nausea and vomiting. A new class of oral agents, the dipeptidyl peptidase-4 inhibitors, is weight-neutral and largely devoid of gastrointestinal side-effects. The cannabinoid receptor antagonist rimonabant is the first of a new class of anti-obesity agents that reduces central obesity and improves multiple aspects of vascular risk.

New agents offer the prospect of improved glycemic control without weight gain. However, the ultimate roles of these agents in the treatment of obese patients with type 2 diabetes remain to be established.