Results from the SCALE™ Obesity and Pre-diabetes phase 3a trial are were presented for the first time at the 23rd Annual Congress of the American Association of Clinical Endocrinologists (AACE) on 16 May 2014. Data showed that after 56 weeks of treatment, liraglutide 3 mg, in combination with diet and exercise, provided significantly greater weight loss of 8 percent (8.4 kg) from baseline compared to 2.6 percent (2.8 kg) with placebo (p1 This is the largest trial in the SCALE™ programme investigating liraglutide 3 mg, an investigational once-daily glucagon-like peptide-1 (GLP-1) analogue for weight management.
All treatment arms included a reduced-calorie diet and increased physical activity. The proportion of adults achieving weight loss of 5 percent or more of their baseline body weight was 64 percent for liraglutide 3 mg treatment compared to 27 percent for placebo (p1
"It is known that a sustained weight loss of 5 to 10 percent provides significant health benefits for adults with obesity," said Dr Xavier Pi-Sunyer, Co-Director of The New York Obesity Nutrition Research Center and lead investigator of the trial. "The high proportion of adults achieving this clinically meaningful weight loss is encouraging, particularly when seen in combination with the additional benefits beyond weight loss that are also being evaluated with liraglutide 3 mg treatment."
In conjunction with weight loss, treatment with liraglutide 3 mg significantly reduced waist circumference by -8.19 cm, compared to -3.94 cm with placebo (p2 Furthermore, treatment with liraglutide 3 mg improved blood glucose levels, blood pressure and lipids levels.1
The most frequently reported side effects associated with liraglutide 3 mg treatment were gastrointestinal (nausea and diarrhoea), which were mild to moderate, occurred shortly after liraglutide initiation, and were transient. Incidences of gallbladder disorders and pancreatitis were low but higher than in placebo-treated individuals.
Gallbladder disorders were reported as 2.7 events per 100 patient-years of exposure (PYE) with liraglutide 3 mg treatment compared to 1.0 events per 100 PYE for placebo and pancreatitis as 0.3 events per 100 PYE with liraglutide 3 mg compared to 0.1 events per 100 PYE with placebo.1
In December 2013, Novo Nordisk submitted a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) and a New Drug Application (NDA) to the US Food and Drug Administration (FDA) for liraglutide 3 mg for chronic weight management in adults who have obesity (BMI ≥30 kg/m2), or are overweight (BMI ≥27 kg/m2) with comorbidities, as an adjunct to a reduced-calorie diet and increased physical activity.3, 4 These applications are under review.
About liraglutide 3 mg
Liraglutide 3 mg is a once-daily glucagon-like peptide-1 (GLP-1) analogue with 97 percent similarity to naturally occurring human GLP-1, a hormone that is released in response to food intake. 5 Like human GLP-1, liraglutide 3 mg regulates appetite and food intake by decreasing hunger and increasing feelings of fullness and satiety after eating.6,7 The dual actions of liraglutide 3 mg on both appetite and blood glucose regulation (for adults with pre-diabetes or type 2 diabetes) hold therapeutic potential for adults with obesity, both those with and without diabetes.
Liraglutide 3 mg is an investigational product and is not approved by the EMA or FDA. Liraglutide is currently available at lower doses (1.2 and 1.8 mg once-daily) as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes, and is not approved for weight management.
About SCALE™ Obesity and Pre-diabetes
The SCALE™ Obesity and Pre-diabetes trial is a randomised, double-blind, placebo-controlled, multinational trial in non-diabetic obese subjects and non-diabetic overweight subjects with co-morbidities. There were 3,731 participants randomised to treatment with liraglutide 3 mg or placebo in combination with diet and exercise. In addition, participants were further stratified to 56 weeks or 160 weeks of treatment based on pre-diabetes status at screening.
The objectives of this trial were to demonstrate clinically meaningful weight loss at 56 weeks as well as investigate the long-term efficacy of liraglutide 3 mg to delay the onset of type 2 diabetes in subjects with pre-diabetes status at screening.
It is the largest of the phase 3a trials in the SCALE™ clinical development programme, which encompassed more than 5,000 participants who are obese or overweight with comorbidities. Further SCALE™ Obesity and Pre-diabetes data will be published and presented later this year.