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 .)

Efficacy and safety of exenatide once weekly versus metformin, pioglitazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): a 26-week double-blind study.

To test the safety and efficacy of exenatide once weekly (EQW) compared with metformin (MET), pioglitazone (PIO), and sitagliptin (SITA) over 26 weeks, in suboptimally treated (diet and exercise) drug-naive patients with type 2 diabetes

Estrogen receptor alpha dinucleotide repeat polymorphism in Japanese patients with autoimmune thyroid diseases

<p>Abstract</p> <p>Background</p> <p>The autoimmune thyroid diseases (AITDs), comprising Graves' disease (GD) and Hashimoto's thyroiditis (HT), appear to develop as a result of complex interactions between predisposing genes and environmental triggers. Susceptibility to AITDs is conferred by genes in the human leukocyte antigen (HLA) and genes unlinked to HLA, including the CTLA-4 gene. Recently, an association to some estrogen receptor (ER)α genotypes with breast cancer, hypertension, osteoporosis, generalized osteoarthritis, and some autoimmune diseases such as rheumatoid arthritis has been reported. We have analyzed a dinucleotide (TA)n repeat polymorphism lying upstream of the human ERα gene in patients with AITDs and in normal subjects.</p> <p>Results</p> <p>Seventeen different alleles were found in 130 patients with GD, 93 patients with HT, and 190 control subjects. There was no significant difference in the distributions of ERα alleles between patients and controls.</p> <p>Conclusions</p> <p>The present results do not support an association between the ERα gene and AITD in the Japanese population.</p

Epidemiology of osteoporotic hip fractures in Spain

We conducted a multicentre study, divided into a retrospective and a prospective portion. The retrospective study evaluated osteoporotic hip fractures that occurred during 2002. The prospective study evaluated osteoporotic hip fractures that occurred during May 2003. The study was conducted in 77 hospitals in Spain and comprised patients 60 years of age and over. In the retrospective study we registered 13,195 hip fractures. Of the patients, 74% were women and 26% were men. The mean age was 80.7±8.4 years. The average incidence was 6.94±0.44 hip fractures per 1,000 inhabitants/year (95% CI, 6.07–7.82). In the prospective study, we registered 1,399 hip fractures. This represents a monthly incidence of 0.60±0.04 hip fractures per 1,000 inhabitants/year (95% CI, 0.51–0.69). Of the subjects, 74% were women and 26% were men. The mean age was 81.4±8.1 years. Using these data, we calculated the average annual prevalence in 2003 to be 7.20 fractures per 1,000 inhabitants. Thirty-three percent had previously suffered a hip fracture. Prior to the fracture, only 18% had received medical treatment for osteoporosis. After discharge from the hospital, only 26% were receiving pharmacological treatment for osteoporosis