with type 2 diabetes mellitus (T2DM), the physiologic glucagon-like peptide-1 (GLP-1) response, which is involved in glucose regulation through several mechanisms, is dysfunctional. GLP-1 receptor agonists can fill an unmet therapeutic need in the treatment of T2DM: improving glycemic control without increasing the risk of hypoglycemia (except with concomitant sulfonylureas) and reducing weight in a substantial proportion of patients. GLP-1 receptor agonists have impacted established disease treatment algorithms for T2DM. For example, in 2009 the American Diabetes Association and European Association for the Study of Diabetes revised their consensus treatment algorithm to incorporate GLP-1 receptor agonists. GLP-1 receptor 4SC-202 agonists were originally represented by exenatide BID (ExBID), a short-acting agent requiring twice-daily injections at meal-time. The longer-acting agent liraglutide, requiring once-daily injections, recently received regulatory approval. Several other long-acting agents are in clinical development, selleck chemicals one of which is the once-weekly formulation of exenatide (exenatide once weekly [ExQW]). This article reviews the clinical
development of ExQW in the DURATION program. Patients in theses clinical trials were receiving various background treatments, ranging from lifestyle therapy to combination oral therapy, although the majority
(68%) received metformin monotherapy. Specifically, safety, glycemic control, and weight were compared in patients treated with ExQW versus ExBID, sitagliptin, pioglitazone, or insulin glargine. Moreover, measures of beta-cell function, cardiovascular risk, inflammation, and hepatic health were investigated. During ExQW clinical development, consistent clinical efficacy (glycosylated hemoglobin, -1.5% to -1.9%; weight, -2kg to -4 kg) and safety data were observed in patients with T2DM treated with ExQW.”
“The influence of strain on the thermally induced dewetting mechanism selleck inhibitor of silicon films is reported. This study shows that the initial strain level in the silicon film significantly affects the final size and shape of the silicon agglomerates resulting from the film dewetting. With the increase of the biaxial strain up to 1.6%, the size of the silicon agglomerates is significantly reduced while their density increases. Moreover, the shape of the agglomerates becomes elongated when the strain favors one of the in-plane crystallographic directions to minimize the total energy of the system. A quantitative analysis of the dewetting mechanism is presented in terms of the agglomerates size and density versus the strain level. Finally, phenomenological laws are extracted, which predict the size and shape of the agglomerates. (C) 2013 AIP Publishing LLC.