Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Experimental study of trimuon events in neutrino charged-current interactions

This Letter reports on a study of trimuon events induced by neutrino interactions in the CHORUS calorimeter exposed to the CERN SPS wide-band v(mu) beam. Among the multimuon events produced in the calorimeter, 42 mu(-) mu(-) mu(+) events were selected and their kinematical properties investigated. In the past, several groups collected a sample of about one hundred events of this type but their source was largely unknown. Taking advantage of experimental data presently available on the production and muonic branching ratios of light neutral mesons and resonances, we make absolute predictions for the expected rates in our experiment. Detailed Monte Carlo simulations described in this article show that more than half of the trimuon events can be attributed to this source. Muons from pi- and K- decays in charm dimuon events are responsible for an additional approximate to 25% contribution to the total mu(-)mu(-)mu(+) rate. The remaining 25% of events are likely to come from the internal bremsstrahlung of virtual photons into a muon pair. Associated-charm production with subsequent decays of both charmed particles into muons is a negligible source of trimuon events. (C) 2004 Elsevier B.V. All rights reserved. RI Doucet, Mathieu/A-5333-2010; Ludovici, Lucio/F-5917-2011; De Rosa, Gianfranca/E-8737-2012; Fiorillo, Giuliana/A-2248-201