Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Novel bicyclo[2.2.0]hexane-fused [60]fullerene derivatives via cycloaddition with a cyclobutadiene diester

Diels-Alder reaction between C60 1 and 1,2-dicarbomethoxycyclobutadiene 2 furnished 1:1 adducts 4 and 5 comprising of a strained [60]fullerene fused bicyclo[2.2.0]hexane moiety

Cycloaddition of a polycyclic 1,3-cyclohexadiene to C<SUB>60</SUB>: an approach towards installing carbocyclic cages on carbon cages

The first cycloadduct between C60 and a 1,3-cyclohexadiene derivative has been characterized

Characterization of [n]-ladderanes of unprecedented length: a new record for fused carbocyclic arrays

This article does not have an abstract

[n]-Ladderanes: a modular access to norbornyl-fused spacer rods

A cycloaddition cascade between norbornene and 1,2-dicarbomethoxycyclobutadiene provides ready access to norbornyl-fused [n]-ladderanes, which undergo further cycloaddition to 1,3-cyclopentadiene to deliver arrays with norbornyl moieties at both the ends. A short synthesis of norbornyl-fused [8]-ladderane is described