Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor 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. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

OMERACT Filter Evidence Supporting the Measurement of At-work Productivity Loss as an Outcome Measure in Rheumatology Research.

Indicators of work role functioning (being at work, and being productive while at work) are important outcomes for persons with arthritis. As the worker productivity working group at OMERACT (Outcome Measures in Rheumatology), we sought to provide an evidence base for consensus on standardized instruments to measure worker productivity [both absenteeism and at-work productivity (presenteeism) as well as critical contextual factors]

Worker productivity outcome measures: OMERACT filter evidence and agenda for future research

The objective of the Outcome Measures in Rheumatology (OMERACT) Worker Productivity working group is to identify worker productivity outcome measures that meet the requirements of the OMERACT filter. At the OMERACT I I Workshop, we focused on the at-work limitations/productivity component of worker productivity (i.e., presenteeism) an area with diverse conceptualization and instrumentation approaches. Various approaches to quantify at-work limitations/productivity (e.g., single-item global and multi-item measures) were examined, and available evidence pertaining to OMERACT truth, discrimination, and feasibility were presented to conference participants. Four candidate global measures of presenteeism were put forth for a plenary vote to determine whether current evidence meets the OMERACT filter requirements. Presenteeism globals from the Work Productivity and Activity Impairment Questionnaire (72% support) and Rheumatoid Arthritis-specific Work Productivity Survey (71% support) were endorsed by conference participants; however, neither the presenteeism global item from the Health and Work Performance Questionnaire nor the Quantity and Quality method achieved the level of support required for endorsement at the present time. The plenary was also asked whether the central item from the Work Ability Index should also be considered as a candidate measure for potential endorsement in the future. Of participants at the plenary, 70% supported this presenteeism global measure. Progress was also made in other areas through discussions at individual breakout sessions. Topics examined include the merits of various multi-item measures of at-work limitations/productivity, methodological issues related to interpretability of outcome scores, and approaches to appraise and classify contextual factors of worker productivity. Feedback gathered from conference participants will inform the future research agenda of the working group