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

Testing the effectiveness and phytotoxicity of post-emergence herbicides in faba beans

Comunicación presentada al XVI Congreso de la Sociedad Española de Malherbología, celebrado en la Universidad Pública de Navarra, Pamplona-Iruña, entre los días 25 y 27 de octubre de 2017.La escasez de materias activas herbicidas de post-emergencia autorizadas en habas y la dificultad en el control de malas hierbas en este cultivo nos ha llevado a la evaluación de la eficacia en el control y fitotoxicidad sobre el cultivo de 7 herbicidas de post-emergencia a las dosis máximas autorizadas en el cultivo o país empleados. Ninguno de los productos resultó totalmente eficaz y selectivo para el cultivo de las habas. Algunos resultaron más eficaces que el único herbicida de post-emergencia autorizado (bentazona al 48%), este es el caso de la bentazona 87%, el cual presentó ligera fitotoxicidad en Tomejil. Entre los herbicidas ensayados la metribuzina 70% presentó en general el control más eficaz, pero mostró una alta fitotoxicidad. Buena eficacia también se observó con imazamox 4% y 2,4-DB 40%, aunque en ambos aparecieron síntomas de fitotoxicidad pero más leves que los anteriores. Para conseguir un control eficaz y selectivo que reduzca la fitotoxicidad en el cultivo, será necesario ajustar dosis y establecer estrategias de control mediante el uso combinado de herbicidas de pre y post-emergencia.The lack of post-emergence herbicides authorized and the difficult of weed control in faba beans are two of the main reasons of the decrease of the cultivated area. In order to provide new herbicides that let a sustainable faba beans crop, a field trial has been carried out in two locations to evaluate the efficacy of weed control and the crop phytotoxicity of 7 post-emergence herbicides authorized in different crops and countries in faba beans. None of the products was completely effective and/or selective, although some were more effective than the unique post-emergence herbicide authorized (bentazona 48%). That was the case of bentazona 87% which only showed slight phytotoxicity in Tomejil. Among the tested herbicides, metribuzina 70% performed the most efficient control but produced high phytotoxicity. Also imazamox 4% and 2,4 DB 40% were efficient and showed phytotoxicity although the symptoms were lower. In order to achieved an efficacy in weed control and a higher selectivity for the crop, adjust dose of these herbicides will be needed and to look for other alternatives, such as combinations of pre and post-emergence products.Al proyecto sectorial de investigación en innovación del IFAPA, AVA.AVA201601.17 por el contrato de C. Alcántara