Burcelin_2008_Diabetes.Metab_34_627

The first antidiabetic agent was a hormone--insulin--and ever since, all therapeutic strategies have been based on the synthesis of chemical compounds to bind its receptors or transcription factors, or to trigger its intracellular mechanisms. Eighty years on, new therapeutic molecules are available for the treatment of diabetes and, again, are based on a hormone--glucagon-like peptide-1 (GLP-1). Whereas the theoretical benefit of insulin is based on normalization of functional physiology, therapeutic strategies based on GLP-1 aim to increase the circulating concentration of a natural component--the hormone GLP-1. There are two strategies for increasing GLP-1 plasma concentrations: replace the hormone with a long-acting analogue or molecule with a longer half-life; and prevent its degradation by inhibiting its natural protease, dipeptidyl peptidase IV (DPPIV). Although numerous clinical trials have been carried out and vast amounts of data are available, the mechanisms through which GLP-1-based therapy reduces blood glucose in diabetic patients remain unclear. Thus, it is essential to ask the right questions and to design appropriate clinical trials and experiments to increase our understanding of the mode of action of GLP-1-based therapy. For this reason, in the spring of 2008, expert scientists and clinicians in the field of GLP-1 got together for an intensive debate on the subject at the first meeting of the European Club for the study of GLP-1, held in Marseille. The subject of the round table discussions was: what is known, new and controversial about GLP-1? During these discussions, numerous facts and controversies were reevaluated, and revealed that several long-held, dogmatic beliefs have never been fully and scientifically established. These points are detailed here in these minutes of the landmark meeting.