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 .)

Flexible and Redox-Active Coordination Polymer: Control of the Network Structure by Pendant Arms of a Macrocyclic Complex

The coordination polymer {[Ni(C(20)H(32)N(8))](2)[TCM]}center dot 5DMF center dot 8H(2)O (1) has been assembled from a Ni(II) macrocyclic complex that contains two pyridyl pendant arms, [Ni(C(20)H(32)N(8))(ClO(4))(2), and sodium tetrakis[4-(carboxyphenyl)oxamethyl]methane (Na(4)TCM) in DMF/water. The X-ray structure of 1 reveals that the pyridyl pendant arms in the macrocyclic complex play a crucial role in determining the network structure through the pi-pi interactions. Compound 1 forms doubly catenated rhombic grids that generate 11) channels. It exhibits flexible behavior upon desorption/resorption and exchange of organic guest molecules as well as temperature change. Solid 1 is redox active due to the incorporated Ni(II) macrocyclic species, and reacts with Pd(NO(3))(2) dissolved in acetonitrile at room temperature to produce small Pd nanoparticles[(2.9 +/- 0.4) nm in diameter] in the channels in the absence of extra reducing or capping agents.close141