Novo Nordisk, a global healthcare company, has reported headline results from a 56-week double-blind phase III a clinical trial investigating the potential of liraglutide to induce and maintain weight loss in people without diabetes who are obese or overweight with comorbidities such as prediabetes, hypertension and dyslipidaemia. This is the third phase IIIa trial to be completed as part of SCALE, the clinical development programme for liraglutide 3 mg as an obesity treatment.
In the trial, 3,731 overweight or obese people were randomised 2:1 to treatment with liraglutide 3 mg or placebo, both in combination with diet and exercise. In the trial, people without signs of prediabetes were treated for 56 weeks, followed by a 12-week follow-up period. People with signs of prediabetes at the time of randomisation are currently continuing treatment for two additional years. The announced results are for all people at 56 weeks.
From a mean baseline weight of 106 kg and a BMI of 38 kg/m2, the average weight loss for people treated with liraglutide 3 mg at 56 weeks was 8.0 per cent compared to 2.6 per cent for people treated with placebo. The proportion of people achieving a weight loss of at least five per cent was 64 per cent for liraglutide 3 mg and 27 per cent for placebo. The proportion of people achieving a weight loss of at least 10% was 33% for liraglutide 3 mg and 10 per cent for placebo treatment. All differences between liraglutide and placebo were statistically significantly different and the trial met all three co-primary endpoints.
Of all people participating in the trial, 61 per cent had prediabetes at randomisation. At 56 weeks, 69 per cent of the prediabetes subgroup treated with liraglutide 3 mg no longer showed signs of prediabetes, compared to 33 per cent for the placebo-treated group. Of the 39 per cent of the people without prediabetes at randomisation, seven per cent of the liraglutide 3 mg treated people developed prediabetes, compared to 21 per cent of the people in the placebo group. Both differences between liraglutide 3 mg and placebo were statistically significant.
Finally, people treated with liraglutide 3 mg experienced statistically significant improvements in obesity-related risk factors, including blood pressure, cardiovascular risk biomarkers, lipids and patient-reported quality of life, compared to people treated with placebo.
In the trial, liraglutide was generally well tolerated. The 56-week completion rate was 72 per cent and 64 per cent for liraglutide 3 mg and placebo, respectively. Withdrawals due to adverse events were below 10 per cent in both treatment groups. The most common adverse events were related to the gastrointestinal system and they diminished over time.
“We are very pleased with the results of this trial,” said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. “These data, together with previously reported phase III trials, consistently demonstrate clinically significant weight loss and improvements in obesity-related risk factors in people with obesity.”
Novo Nordisk expects to complete the remaining phase IIIa trial in the SCALE programme in the third quarter of 2013 and to file liraglutide 3 mg for regulatory review as a treatment for obesity in the US and EU around the turn of the year.
Liraglutide 3 mg is a once-daily GLP-1 analogue with 97 per cent homology to human GLP-1. Like human GLP-1, liraglutide 3 mg acts as a natural satiety hormone to reduce appetite and food intake. Liraglutide 3 mg is not an approved treatment. Liraglutide is currently approved and marketed at lower doses (1.2 and 1.8 mg oncedaily as well as 0.9 mg in Japan) for type 2 diabetes only, under the brand name Victoza. Victoza is not approved for weight management and should not be prescribed for its treatment.
SCALE (Satiety and Clinical Adiposity – Liraglutide Evidence in Non-diabetic and Diabetic people) consists of four trials encompassing more than 5,000 people who are overweight (BMI =27 kg/m2) and with comorbidities such as hypertension, dyslipidaemia, or type 2 diabetes or who are obese (BMI =30 kg/m2) with or without comorbidities. In addition to demonstrating safety and efficacy for weight management with liraglutide 3 mg, each of the four trials has its own distinct focus: SCALE Maintenance (422 people randomised) – a 56-week randomised, placebocontrolled trial designed to show weight loss maintenance in obese or overweight people with comorbidities who have successfully achieved a five per cent or greater weight loss during a three-month run-in period of a lifestyle modification programme of low-calorie diet and exercise alone. The results of SCALE™ Maintenance were reported in 2010.
SCALE Diabetes (846 people randomised) – a 56-week randomised, placebo-controlled trial designed to demonstrate clinically meaningful and safe weight loss with liraglutide 3 mg in obese or overweight people with type 2 diabetes. The results of SCALE Diabetes were reported in March 2013.
SCALE Obesity and Prediabetes (3,731 people randomised) – a 56-week and 160-week randomised, placebo-controlled trial in obese or overweight people with comorbidities designed to demonstrate clinically meaningful and safe weight loss after 56 weeks of treatment with liraglutide 3 mg.Page 3 of 3
SCALE Sleep apnoea (approximately 340 people randomised) – a 32-week randomised, double-blind, placebo-controlled trial in obese people with moderate or severe obstructive sleep apnoea (OSA) to investigate the effect of liraglutide 3 mg in reducing the severity of OSA, in combination with diet and exercise.
Novo Nordisk is a global healthcare company with 90 years of innovation and leadership in diabetes care.