New Phase 3a Liraglutide 3 mg Data Showed Positive Impact on Cardiovascular Risk Markers and Fewer People Progressing to Pre-Diabetes Compared With Placebo in Adults With Obesity

CHICAGO, June 21, 2014 /PRNewswire/ --

Today, new data from the phase 3a SCALE™ Obesity and Pre-diabetes trial were presented at the International Congress of Endocrinology (ICE) and the Endocrine Society's meeting (ENDO). In addition to a greater body weight loss, significantly fewer people with obesity and normal blood glucose at baseline progressed to pre-diabetes with liraglutide 3 mg treatment (6.9%) at 56 weeks, compared with placebo (19.9%, P<0.0001). Additionally, liraglutide 3 mg treatment resulted in improvements in a wide range of cardiovascular disease risk markers, compared with placebo. Individuals in the trial with pre-diabetes are continuing in their randomised cohort for an additional two years.

All treatment groups followed a reduced-calorie diet and increased physical activity programme. In addition to a clinically meaningful body weight loss of 8% from baseline (vs. 2.6% with placebo, P<0.0001), people without diabetes treated with liraglutide 3 mg experienced significantly greater improvements in their blood glucose levels compared to people on placebo (A1Cestimated treatment difference [ETD]:-0.23%, P<0.0001). Furthermore, improvements in insulin secretion and sensitivity were observed in adults treated with liraglutide 3 mg, with and without pre-diabetes.

"Many risk factors need to be considered in the management of obesity, as it can be associated with a number of comorbidities, including heart disease and type 2 diabetes," said Dr. Xavier Pi-Sunyer, Co-Director of The New York Obesity Nutrition Research Center and lead investigator of the trial. "It's encouraging to see the weight loss demonstrated by liraglutide 3 mg, combined with the improvements in blood glucose levels and other cardiovascular risk factors such as blood pressure and lipids."

Results from the pre-diabetes group demonstrated that at 56 weeks people treated with liraglutide 3 mg experienced a higher rate of pre-diabetes reversal compared with placebo; 69.7% of people reverted to normal blood glucose levels (32.1% with placebo, P<0.0001). A greater number of people progressed to type 2 diabetes with placebo (1.3 events per 100 patient-years of exposure [PYE], n=14) compared with liraglutide 3 mg (0.2 events per 100 PYE, n=4; P=0.0003).

In the trial, treatment with liraglutide 3 mg resulted in improvements in a wide range of cardiovascular risk factors and inflammatory markers compared with placebo:

• Greater reduction in blood pressure (systolic blood pressure: ETD -2.8 mm Hg; diastolic blood pressure: ETD -0.9 mm Hg, P<0.001)
• Improvement in fasting lipids, including low-density lipoprotein cholesterol (ETD -2%, P<0.01), high-density lipoprotein cholesterol (ETD 2%, P<0.01) and triglycerides (ETD -9%, P<0.0001)
• Greater reduction in the use of blood-pressure-lowering and lipid-lowering medications

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. Side effects leading to withdrawal occurred in 9.9% of people treated with liraglutide 3 mg, which were primarily gastrointestinal, compared to 3.8% with placebo, and serious adverse events were similar across treatment groups (liraglutide 3 mg, 6.3% vs. placebo, 5.0%).

Incidences of gallbladder disorders and pancreatitis were low but higher than in placebo-treated individuals. Gallbladder-related adverse events were reported as 3.1 events per 100 PYE with liraglutide 3 mg treatment compared to 1.4 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. The mean pulse rate was 2.4 beats per minute higher with liraglutide 3 mg than with placebo. Cardiovascular events reported were similar across treatment groups, but higher in people treated with placebo (liraglutide 3 mg, 8.7% vs. placebo, 9.9%).

In December 2013, based on the results of the SCALE™ clinical development programme, Novo Nordisk submitted a New Drug Application and a Marketing Authorisation Application to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), respectively, for liraglutide 3 mg for chronic weight management in adults who have obesity (BMI ≥30 kg/m^[2]), or are overweight (BMI ≥27 kg/m^[2]) with comorbidities, as an adjunct to a reduced-calorie diet and increased physical activity.^[1] 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% similarity to naturally occurring human GLP-1,^[2] a hormone that is released in response to food intake. Like human GLP-1, liraglutide 3 mg regulates appetite and food intake by decreasing hunger and increasing feelings of fullness and satiety after eating.^[3],[4]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 people with obesity, both those with and without type 2 diabetes.

Liraglutide 3 mg is an investigational product and is not approved by the FDA or EMA.

About SCALE™ Obesity and Pre-diabetes  

The SCALE™ Obesity and Pre-diabetes^[5] trial is a randomised, double-blind, placebo-controlled, multinational trial in non-diabetic people with obesity and non-diabetic people who are overweight with comorbidities. 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 to investigate the long-term efficacy of liraglutide 3 mg to delay the onset of type 2 diabetes in participants with pre-diabetes at screening.

It is the largest of the phase 3a trials in the SCALE™ clinical development programme, which encompassed more than 5,000 people with obesity or people who are overweight with comorbidities.

About Novo Nordisk 

Headquartered in Denmark, Novo Nordisk is a global healthcare company with 90 years of innovation and leadership in diabetes care. The company also has leading positions within haemophilia care, growth hormone therapy and hormone replacement therapy. Novo Nordisk employs approximately 40,000 employees in 75 countries, and markets its products in more than 180 countries. For more information, visit  novonordisk.com. 

References 

1. Data on file. Novo Nordisk Inc; Plainsboro, NJ.  

2. Knudsen LB, Nielsen PF, Huusfeldt PO. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem. 2000;43(9):1664-1669. 

3. Flint A, Raben A, Ersboll AK, Holst JJ, Astrup A. The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity. Int J Obes. 2001;25(6):781-792.  

4. van Can J, Sloth B, Jensen CB, Flint A, Blaak EE, Saris WHM. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults [published online ahead of print October 1, 2013]. Int J Obes. doi:10.1038/ijo.2013.162. 

5 SCALE™ Obesity and Prediabetes ClinicalTrials.gov study registration: NCT01272219. 

© 2014 Novo Nordisk All rights reserved. 0614-00021803-1 June 2014 

SOURCE Novo Nordisk

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