3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes
3 years of liraglutide versus placebo for type 2 diabetes risk
reduction and weight management in individuals with
prediabetes: a randomised, double-blind trial
Carel W le Roux, Arne Astrup, Ken Fujioka, Frank Greenway, David C W Lau, Luc Van Gaal, Rafael Violante Ortiz, John P H Wilding, Trine V Skjøth,
Linda Shapiro Manning, Xavier Pi-Sunyer, for the SCALE Obesity and Prediabetes NN8022-1839 Study Group*
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.