Confronting the Type 2 Diabetes Epidemic: the Emerging Role of Incretin-based Therapies

This report highlights a roundtable discussion that occurred during the annual meeting of the International Diabetes Federation (IDF) in November 2009, in Montreal, Quebec, Canada. Participants included Bernard Zinman, MD, Michael A. Nauck, MD, PhD, Jorge Plutzky, MD, and Allison B. Goldfine, MD. The roundtable was chaired by Vivian A. Fonseca, MD. Among the topics discussed were the burden of type 2 diabetes mellitus and the importance of "appropriate therapy," which includes not only managing glycemia but also the management of concomitant risk factors such as hypertension and dyslipidemia. The discussants also identified issues that remain to be resolved, such as determining the nature of first-line therapy (e.g., should initial dual-agent therapy be encouraged?) and agreeing upon the most appropriate agent to be combined with metformin, which is the current standard of care. Among the new treatments discussed for type 2 diabetes were the analogues of the incretin hormones glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), namely, the GLP-1 receptor agonists-as well as the inhibitors of dipeptidyl peptidase-4 (DPP-4), the enzyme that regulates the bioactivity of the endogenous incretin hormones. These agents have some interesting advantages; not only do they effectively lower glucose, but they also have demonstrated beneficial metabolic and cardiovascular effects. Particularly with respect to the GIP and GLP-1, weight loss, blood pressure reductions, and beta-cell function improvements have been observed in clinical trials. What remains to be determined, by means of additional clinical experience and perhaps additional head-to-head trials, are the long-term benefits of GLP-1 receptor agonists and DPP-4 inhibitors and the sorts of roles these 2 classes of agents may play in the type 2 diabetes therapeutic continuum.