SCALE Impact Case Study
Liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes
• Study ran between June 2011 – March 2015
• Randomised, double-blind, placebo-controlled trial
• Funded by Novo Nordisk, manufacturers of liraglutide
• An international, multicentre study with several UK sites involved
• The NIHR recruited 99 participants to time and target across seven sites in England
• Globally a total of 3731 people were enrolled on the study
• Chief Investigator: John Wilding, Professor of Medicine at the University of Liverpool, Honorary Consultant Physician and an obesity specialist
Obesity is a major public health issue. One in four adults in England live with obesity and over 60 percent of adults are either overweight or obese. Obesity increases the risk of other health conditions, such as heart disease and stroke, cancer and type 2 diabetes. It also affects quality of life. The associated health care cost to the economy is significant too. In 2007 it was estimated that NHS costs attributed to elevated body mass index (BMI) (overweight and obesity) were £4.2 billion.
This was forecast to rise to £9.7 billion in 2050. The global SCALE study looked at whether a daily injection of the drug liraglutide, alongside diet and exercise, would lead to weight loss in people with obesity or who are overweight. The study also looked at whether liraglutide could reduce incidence of type 2 diabetes in people with prediabetes. Prediabetes is when blood sugar level is higher than normal, but not high enough to be considered diabetes.
The liraglutide injection works by helping people feel fuller after meals, thus reducing their food intake and helping them to lose weight.
Outcomes and findings
The SCALE study was conducted at 191 clinical research sites across 27 countries. 2254 patients were randomly assigned to receive liraglutide 3.0mg or placebo. During the 56-week trial they evaluated the efficacy and safety of daily liraglutide for weight management in people with and without prediabetes. The study showed that a daily injection of the drug liraglutide alongside diet and exercise led to weight loss in people with obesity or who are overweight, reducing risk factors for heart disease and the chances of developing diabetes for those at high risk of the condition.
Weight loss was 8kg in the liraglutide group and 2.6kg in the placebo group after one year. People with prediabetes then entered the three year extension which had the aim of investigating whether liraglutide could delay the onset of type 2 diabetes. The study showed that three years of continuous treatment with a daily injection of liraglutide 3.0mg, in combination with diet and increased physical activity, reduced the risk of developing type 2 diabetes by 80 per cent and led to greater sustained weight loss compared to the placebo. Other risk factors such as blood pressure and lipids also improved to a greater extent with liraglutide than placebo, as did quality of life. The main adverse effects were gastrointestinal, such as nausea, which usually resolved after a few weeks of treatment.
Value to the NHS
There have been few trials of medications to tackle obesity that have lasted three years. This study provides clinically important long-term data on the efficacy and safety of liraglutide 3.0mg in individuals with prediabetes. Liraglutide 3.0mg is approved for use and licensed in the UK. NICE has published an evidence summary (2017) and is currently planning a technology appraisal (recommendations on the use of new and existing medicines and treatments within the NHS). Further research is looking at more potent drugs in the same class that may provide greater weight loss for people with obesity or who are overweight.
“The SCALE study has shown that the drug liraglutide can provide us with a new therapeutic approach for patients with obesity and prediabetes to substantially reduce their risk of developing type 2 diabetes and its related complications.
“Tackling the a obesity epidemic is not as simple as telling people to eat less and exercise more. Obesity is a major public health issue that requires action on so many levels. SCALE is a positive step forward.”
Professor John Wilding, NIHR National Specialty Lead for Metabolic and Endocrine Disorders
• A Double-blind Randomized Controlled Trial New England Journal of Medicine 2015 373:11-22.DOI: 10.1056/NEJMoa1411892
• Exposure-response analyses of liraglutide 3.0mg for weight management. Diabetes, Obesity and Metabolism 2016 18, 5: 491–499,DOI: 10.1111/dom.12639
• Three years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes. Lancet 2017 http://dx.doi.org/10.1016/S0140-6736(17)30069-7