Alogliptin after acute coronary syndrome in patients with type 2 diabetes

Background - To assess potentially elevated cardiovascular risk related to new antihyperglycemic drugs in patients with type 2 diabetes, regulatory agencies require a comprehensive evaluation of the cardiovascular safety profile of new antidiabetic therapies. We assessed cardiovascular outcomes with alogliptin, a new inhibitor of dipeptidyl peptidase 4 (DPP-4), as compared with placebo in patients with type 2 diabetes who had had a recent acute coronary syndrome. Methods - We randomly assigned patients with type 2 diabetes and either an acute myocardial infarction or unstable angina requiring hospitalization within the previous 15 to 90 days to receive alogliptin or placebo in addition to existing antihyperglycemic and cardiovascular drug therapy. The study design was a double-blind, noninferiority trial with a prespecified noninferiority margin of 1.3 for the hazard ratio for the primary end point of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Results - A total of 5380 patients underwent randomization and were followed for up to 40 months (median, 18 months). A primary end-point event occurred in 305 patients assigned to alogliptin (11.3%) and in 316 patients assigned to placebo (11.8%) (hazard ratio, 0.96; upper boundary of the one-sided repeated confidence interval, 1.16; P<0.001 for noninferiority). Glycated hemoglobin levels were significantly lower with alogliptin than with placebo (mean difference, -0.36 percentage points; P<0.001). Incidences of hypoglycemia, cancer, pancreatitis, and initiation of dialysis were similar with alogliptin and placebo. Conclusions - Among patients with type 2 diabetes who had had a recent acute coronary syndrome, the rates of major adverse cardiovascular events were not increased with the DPP-4 inhibitor alogliptin as compared with placebo. (Funded by Takeda Development Center Americas; EXAMINE ClinicalTrials.gov number, NCT00968708.

Thyroid Function and Body Weight: A Community-Based Longitudinal Study

OBJECTIVE: Body weight and overt thyroid dysfunction are associated. Cross-sectional population-based studies have repeatedly found that thyroid hormone levels, even within the normal reference range, might be associated with body weight. However, for longitudinal data, the association is less clear. Thus, we tested the association between serum thyrotropin (TSH) and body weight in a community-based sample of adult persons followed for 11 years. METHODS: A random sample of 4,649 persons aged 18-65 years from a general population participated in the DanThyr study in 1997-8. We included 2,102 individuals who participated at 11-year follow-up, without current or former treatment for thyroid disease and with measurements of TSH and weight at both examinations. Multiple linear regression models were used, stratified by sex and adjusted for age, smoking status, and leisure time physical activity. RESULTS: Baseline TSH concentration was not associated with change in weight (women, P = 0.17; men, P = 0.72), and baseline body mass index (BMI) was not associated with change in TSH (women, P = 0.21; men, P = 0.85). Change in serum TSH and change in weight were significantly associated in both sexes. Weight increased by 0.3 kg (95% confidence interval [CI] 0.1, 0.4, P = 0.005) in women and 0.8 kg (95% CI 0.1, 1.4, P = 0.02) in men for every one unit TSH (mU/L) increase. CONCLUSIONS: TSH levels were not a determinant of future weight changes, and BMI was not a determinant for TSH changes, but an association between weight change and TSH change was present