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

Objective: 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.

Methods: 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.

Results: 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.

Conclusions: 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.