3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Para além da paz liberal? respostas ao "retrocesso" Beyond liberal peace? responses to "backsliding"

A ortodoxia familiar de construção da paz liberal depende da transplantação e da exportação de condicionalidade e dependência, com vistas a consolidar um contrato social entre populações, seus governos e o Estado, em que repouse uma paz liberal legítima e consensual. O que, com frequência, ocorre, é uma forma híbrida de paz liberal, sujeita a críticas locais poderosas, à resistência, por vezes, e à percepção de que a construção da paz internacional está fracassando em corresponder às expectativas. Em termos kantianos, os problemas com que a paz liberal tem se deparado e a crise pela qual está hoje passando podem ser denominados "retrocesso". Tem sido particularmente notável que a construção da paz liberal não vem sendo capaz de construir políticas unidas a partir de fragmentos territoriais no Kosovo, na Bósnia, no Afeganistão, no Iraque, no Sri Lanka e mesmo na Irlanda do Norte, onde alguns ou todos de seus elementos estão em desenvolvimento. Isso indica uma necessidade ou de reforma do modelo liberal para a paz, ou de estabelecimento de uma capacidade de coexistência desse modelo com alternativas, ou de substituição do modelo. Este artigo examina uma gama de questões inerentes ao paradigma de construção da paz liberal, algumas causas de "retrocesso" e o que pode ser feito no que tange a tais causas, no sentido de utilizar a construção da paz para criar um novo contrato social e atingir o que se poderia muito bem ser uma forma "híbrida liberal-local" de paz.<br>The familiar orthodoxy of liberal peacebuilding depends upon transplanting and exporting conditionality and dependency in order to cement a social contract between populations, their governments and the state, on which rests a legitimate and consensual liberal peace. What often emerges is a hybrid form of the liberal peace, subject to powerful local critiques, sometimes resistance, and to the perception that international peacebuilding is failing to live up to expectations. In Kantian terms, the problems that the liberal peace has faced, and the crisis that it is now in, can be termed "backsliding". It has been particularly notable that liberal peacebuilding has not been able to build united polities from territorial fragments in Kosovo, Bosnia, Afghanistan, Iraq, Sri Lanka, and even in Northern Ireland, where some or all if its elements are in development. This indicates a need for a reform of the liberal model for peace, or to establish a capacity for it to coexist with other alternatives, or to replace it. This article examines a range of issues inherent in the liberal peacebuilding paradigm, some causes of backsliding, and what might be done about them in terms of using peacebuilding to create a new social contract and to arrive at may well be a "liberal-local hybrid" form of peace