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.

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SUMMARYAim: To study 5-aminosalicylate nephrotoxicity in patients with inflammatory bowel disease in the UK.

Aim Evaluation of stress and its causes in UK gastroenterologists, Design Questionnaire emailed to all 1932 medical members of the British Society of Gastroenterology. Results Of 567 respondents (29%), 107 (20%) graded their stress level as 4 or 5 out of 5. Stress levels correlated inversely with selfreported happiness levels (r=−0.60; p<0.001) and with hours slept per night (r=−0.23; p<0.01) and correlated directly with % time off-duty thinking about work (r=0.46; p<0001) and with proportion of nights with broken sleep (r=0.30; p<0.01). Due to stress over the past year, 21% of respondents reported one of the following: consulting their general practitioner (7%), attending occupational health (5%), taking planned time off (7%), taking anxiolytics/antidepressants (6%) and considering suicide (5.5%). These respondents had higher stress and lower happiness levels than the remainder. Stress levels were higher in women and in those working full time but had no other demographic associations. The main causes of stress were excessive clinical work (ranked highest by 47% and most commonly patient-related administration), working conditions beyond control (ranked highest by 15% and most commonly inadequate information technology systems, workspace and secretarial staff) and conflict (ranked highest by 9%). Of eight potential factors, happiness with work showed the closest associations with overall happiness (positive) and overall stress (negative) levels. Talking to someone at work about stress was ranked difficult or impossible by 35%. The highest ranked suggested solutions were relief from some duties and mentoring.Conclusions Stress is common and has objective correlates in UK gastroenterologists. The main cause is excessive workload.