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HomeA Focus'Groundbreaking' weight loss drug slashes type 2 diabetes risk

'Groundbreaking' weight loss drug slashes type 2 diabetes risk

CarlFocusA weight loss drug has reduced the risk of type 2 diabetes by 80% compared to placebo. Study author Professor Carel le Roux, University of Pretoria-trained and now at the Imperial College London, said:  'These groundbreaking results could pave the way for a widely used, effective, and safe drug to reverse prediabetes and prevent diabetes … saving millions on healthcare spending.'

The drug, which increases the amount of appetite-supressing hormones produced by the gut, was tested on overweight people with 'prediabetes'. This is also known as 'borderline diabetes,' and is characterised by slightly increased blood sugar levels. The condition often leads to type 2 diabetes when untreated.

Prediabetes affects one in ten people in the UK, and progresses into diabetes in 5%-10% of patients within ten years. Prediabetes is curable with exercise and a healthier diet, but once it progresses into diabetes, it is significantly harder to treat. Both conditions are strongly linked to early death and poor health outcomes like nerve damage, blindness and amputation.

Now, obesity expert Professor Carel le Roux, University of Pretoria-trained and now at the Imperial College London, and colleagues have found that a drug already used for obesity and diabetes can help to prevent progression into diabetes when combined with diet and exercise, and could even cure patients of prediabetes altogether.

The researchers recruited 2,254 obese adults with prediabetes at 191 research sites in 27 countries worldwide. After splitting participants into two groups, they studied whether adding daily self-administered injections of liraglutide to diet and exercise helped to prevent progression into diabetes, compared to diet and exercise alone.

After three years, the researchers found that the patients given liraglutide were 80% less likely to develop diabetes than those in the placebo group. In 60% of those patients, prediabetes was reversed and patients returned to healthy blood sugar levels.

Of the patients who did go on to develop diabetes, those who were given liraglutide took nearly three times longer to develop the disease than those in the placebo group. In addition, liraglutide was linked to greater sustained weight loss after three years compared to placebo, with those on liraglutide losing 7% body weight compared to 2% body weight in the placebo group.

le Roux, from Imperial's department of medicine, said: "These groundbreaking results could pave the way for a widely used, effective, and safe drug to reverse prediabetes and prevent diabetes in 80% of at-risk people. This could improve the health of the population and save millions on healthcare spending." le Roux added that the drug seems to work by mimicking the action of naturally-produced hormone that supresses appetite, called GLP-1. This compound is released in response to food, and interacts with the brain's hypothalamus to suppress appetite.

However previous studies have found that many obese people produce less of this hormone, which may lead to them over-eating. Liraglutide mimics the effects of GLP-1, essentially doing the hormone's job to regulate appetite.

le Roux said: "Liraglutide promotes weight loss by activating brain areas that control appetite and eating, so that people feel fuller sooner after meals and their food intake is reduced. Although liraglutide's role in weight loss is well known, this is the first time it has been shown to essentially reverse prediabetes and prevent diabetes, albeit with the help of diet and exercise."

Liraglutide is already being used to manage weight and diabetes, but it is expensive and not yet widely available in the UK. However, future studies could help develop a test for GLP-1 deficiency, to ensure the drug is given only to those who would benefit. Alternatively, patients could undergo a 12-week trial where the drug is stopped if there is no improvement within that time.

Summary
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.

Authors
Carel W le Roux, Arne Astrup, Ken Fujioka, Frank Greenway, David C W Lau, Luc Van Gaal, Rafael Violante Ortiz, John PH Wilding, Trine V Skjøth, Linda Shapiro Manning, Xavier Pi-Sunyer

[link url="http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_21-2-2017-16-23-58"]Imperial College London material[/link]
[link url="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)30069-7/abstract"]The Lancet article summary[/link]

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