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

Vitamin E Prevents Lipogenesis Dysregulation in the Liver Cells at Old Age Vitamin E Prevents Lipogenesis Dysregulation in the Liver Cells at Old Age

Abstract Thyroid hormones play critical roles in lipogenesis regulation. Genomic dependent and genomic independent effects of triiodothyronine on free fatty acids (FFA) synthesis have been determined. The lipogenesis regulation with L-thyroxine (T4) in the liver cells of 3-and 24-month-old rats and effects of vitamin E (?-tocopherol acetate) or N-acetylcistein (NAC) on old liver response to hormone action have been investigated. T4 in both experiments in vivo and in vitro increased lipogenesis in liver cells of young rats, while old hepatocytes were resistant to the hormone action. Vitamin E as well as N-acetylcistein (NAC) increased significantly the liver and hepatocytes sensitivity to the T4 action at old age. However, the vitamin E-dependent induction of FFA synthesis with T4 was not followed by FFA accumulation. The newly synthesized FFA were used for cholesterol and neutral lipids synthesis in old liver cells treated with T4 plus vitamin E or NAC. The data obtained have demonstrated for the first time that the age-dependent lipogenesis dysregulation depends on redox state changes in liver. Vitamin E improved both the long-term and the short-term genomic independent thyroid hormone lipogenesis regulation at old age