The modulating effects of GLP-1 in type 2 diabetes

Abstract

Introduction The recent development of incretin-based therapies offers the possibility of a paradigm shift in the management of patients with type 2 diabetes. Incretin-based agents provide a different physiological means of lowering blood glucose, by enhancing the insulin response to ingestion of food and inhibiting glucagon secretion. Agents such as the GLP-1 receptor agonist exenatide and the DPP-4 inhibitors sitagliptin and vildagliptin are now available (the latter not in the USA) for utilisation in regimens to treat type 2 diabetes, while the GLP-1 analogue liraglutide may soon be available. Incretinbased therapies offer the possibility of directly influencing the disease process itself through their beneficial effects on the failing β cell. Endogenous GLP-1 is known to be an important factor in maintaining β-cell mass, while reduced levels of this hormone may play a pathogenic role in the development of disease. Preclinical studies indicate that exposure to a GLP1 analogue may help preserve β-cell mass and perhaps attenuate the onset of type 2 diabetes. The following five articles were developed to provide a broad understanding of the potential as well as the outstanding issues concerning these new agents. Four articles were derived from presentations given at a symposium held on 17 September 2007, during the European Association for the Study of Diabetes Annual Meeting in Amsterdam, The Netherlands. Vivian Fonseca (Tulane University, New Orleans, USA) describes the decline of pancreatic β-cell function over time, a hallmark of type 2 diabetes. Then Jens J Holst (University of Copenhagen, Denmark) reviews pharmacological strategies to utilise the beneficial effects of incretin hormones on glucose homeostasis. Baptist Gallwitz (Eberhard-KarlsUniversity of Tubingen, Germany) provides an overview of data from in vitro, preclinical and phase II studies that show promising results with GLP-1 analogues in improving β-cell function in patients with type 2 diabetes. My article will focus on the research concerning liraglutide, a GLP-1 analogue that is very similar to endogenous GLP-1. To complete the overview, Philip Larsen (Eli Lilly and Co., Indianapolis, USA) has contributed an article on the potential for GLP-1 agonists to help regulate body weight, an important issue in type 2 diabetes. Incretin-based therapies are a relatively recent innovation in type 2 diabetes treatment, and the durability of their beneficial effects has yet to be demonstrated in long-term clinical studies. Additional topics of interest for future studies include optimal use within existing treatment strategies and long-term effects on cardiovascular risk factors, and, in the long run, risks. Nevertheless, there is reason to believe that these agents may provide long-term benefits in the management of type 2 diabetes. We hope you find the following articles useful and informative. Br J Diabetes Vasc Dis. 2008; 8 (Suppl 2): S1