Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

No abstract

BackgroundThe objective of this study was to investigate the associations among the mid-pregnancy glycated hemoglobin A1c (HbA1c) level, gestational diabetes (GDM), and risk of adverse pregnancy outcomes in women without overt diabetes and with positive 50-g, 1-h glucose challenge test (GCT) results (140 mg/dL or greater).MethodsThis prospective study enrolled 1,989 pregnant Taiwanese women. A two-step approach, including a 50-g, 1-h GCT and 100-g, 3-h oral glucose tolerance test (OGTT), was employed for the diagnosis of GDM at weeks 23–32. The mid-pregnancy HbA1c level was measured at the time the OGTT was performed. A receiver operating characteristic (ROC) curve was used to determine the relationship between the mid-pregnancy HbA1c level and GDM. Multiple logistic regression models were implemented to assess the relationships between the mid-pregnancy HbA1c level and adverse pregnancy outcomes.ResultsAn ROC curve demonstrated that the optimal mid-pregnancy HbA1c cut-off point to predict GDM, as diagnosed by the Carpenter-Coustan criteria using a two-step approach, was 5.7%. The area under the ROC curve of the mid-pregnancy HbA1c level for GDM was 0.70. Compared with the levels of 4.5–4.9%, higher mid-pregnancy HbA1c levels (5.0–5.4, 5.5–5.9, 6.0–6.4, 6.5–6.9, and >7.0%) were significantly associated with increased risks of gestational hypertension or preeclampsia, preterm delivery, admission to the neonatal intensive care unit, low birth weight, and macrosomia (the odds ratio [OR] ranges were 1.20–9.98, 1.31–5.16, 0.88–3.15, 0.89–4.10, and 2.22–27.86, respectively).ConclusionsThe mid-pregnancy HbA1c level was associated with various adverse pregnancy outcomes in high-risk Taiwanese women. However, it lacked adequate sensitivity and specificity to replace the two-step approach in the diagnosis of GDM. The current study comprised a single-center prospective study; thus, additional, randomized control design studies are required.

Our results identified several oxidative stress markers that may be clinically important in diabetic nephropathy. Studies with larger sample sizes should be undertaken to confirm these findings.