Phase 3a Data Showed Liraglutide 3 mg Demonstrated Significantly Greater Weight Loss Compared to Placebo in Adults With Obesity and Type 2 Diabetes

SAN FRANCISCO, June 14, 2014 /PRNewswire/ --

Today, primary results from SCALE™ Diabetes, a phase 3a clinical trial of liraglutide 3 mg, an investigational once-daily glucagon-like peptide-1 (GLP-1) analogue for chronic weight management, were presented for the first time at the 74^th Annual Scientific Sessions of the American Diabetes Association (ADA) in San Francisco, California. Liraglutide 3 mg, in combination with diet and physical activity, demonstrated statistically significantly greater weight loss at 56 weeks in adults with obesity and type 2 diabetes or who were overweight with type 2 diabetes, compared with placebo.^[1]

All treatment groups included a reduced-calorie diet and increased physical activity. At 56 weeks of treatment, the SCALE™ Diabetes trial showed that adults treated with liraglutide 3 mg achieved significantly greater mean weight loss of 5.9% of baseline body weight compared with 4.6% with liraglutide 1.8 mg (P<0.01), and 2.0% with placebo (P<0.0001). In the trial, 49.9% of people achieved clinically meaningful weight loss of at least 5% when treated with liraglutide 3 mg compared with 35.0% treated with liraglutide 1.8 mg (P<0.001) and 12.7% with placebo (P<0.0001). The proportion of people losing more than 10% body weight was significantly greater with liraglutide 3 mg (22.1 %) compared with liraglutide 1.8 mg (13.3 %) and placebo (3.8%) (P<0.01 and P<0.0001, respectively).^[1]

"Weight loss and weight management are generally much harder for people who are overweight or obese and who also have type 2 diabetes," said Dr. Robert Kushner, Clinical Director, Northwestern Comprehensive Center on Obesity, Chicago. "Given the challenges faced by this patient population, the 5.9% weight loss seen with liraglutide 3 mg in this study is impressive. There is a real need for effective treatment options for adults with obesity and type 2 diabetes that can demonstrate clinically meaningful weight loss and improve serious weight-related comorbidities."

In addition to weight loss, a significantly greater reduction in blood glucose (HbA_1c) from baseline was observed with liraglutide 3 mg (-1.3%) compared with placebo (-0.4%) after 56 weeks of treatment (P<0.0001), with significantly more people achieving HbA_1c target of less than 7% with liraglutide 3 mg (72.3%) compared with placebo (22.9%, P<0.0001). Significant reductions in HbA_1c were observed with liraglutide 1.8 mg compared with placebo (-1.1% vs. -0.4%, P<0.0001) and statistically more people achieved HbA_1c target (<7%) with liraglutide 1.8 mg compared with placebo (69.6% vs. 22.9%, P<0.0001).^[1]

The most frequently reported side effects were gastrointestinal disorders (driven by nausea and diarrhea), and occurred in 65% of people treated with liraglutide 3 mg compared with 56% with liraglutide 1.8 mg and 39% with placebo. The most common adverse events (AEs) occurring in more than 5% of people treated with liraglutide 3 mg included hypoglycemia, decreased appetite, abdominal distension, abdominal pain, dyspepsia, flatulence, vomiting, constipation, nasopharyngitis, usually referred to as the common cold, upper respiratory tract infection, influenza, back pain, musculoskeletal pain, arthralgia, headache, dizziness, fatigue and increased lipase. The most frequent side effects leading to withdrawal from the liraglutide 3 mg treatment group were gastrointestinal disorders (5.7%).^[1]  

In December 2013, based on the results of the SCALE™ clinical development program, Novo Nordisk submitted a New Drug Application (NDA) and a Marketing Authorization Application (MAA) to the US 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.^[2] These applications are under review.

Liraglutide is currently available in the US at a lower dose (1.2 mg and 1.8 mg) under the brand name Victoza^® (liraglutide [rDNA origin] injection) for treatment of adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve blood glucose control. Victoza^® is not approved for weight management.^[3]

The FDA recommends that any investigational product being developed for weight management should be investigated in people with type 2 diabetes, as overweight and obese patients with type 2 diabetes often respond less favorably to weight-management medications.^[4] The FDA requested the inclusion of liraglutide 1.8 mg (Victoza^® [liraglutide (rDNA origin) injection]) in the SCALE™ Diabetes study to bridge to the safety and efficacy data for Victoza^® in the treatment of adults with type 2 diabetes.

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,^[5] 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.^[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 type 2 diabetes.

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

About SCALE™ Diabetes  

SCALE™ Diabetes is a multinational 56-week, randomized, placebo-controlled, double-blind phase 3a clinical trial involving 846 adults with obesity or who are overweight, and with type 2 diabetes. It was designed to demonstrate clinically meaningful and safe weight loss with liraglutide 3 mg in this population. It is one of four trials in the SCALE™ clinical development program, which encompassed more than 5,000 participants who are obese with or without comorbidities or overweight with comorbidities.

About Victoza^®  

Victoza^® is a human glucagon-like peptide-1 (GLP-1) analog that was approved by the U.S. Food and Drug Administration on January 25, 2010, as an adjunct to diet and exercise to improve blood sugar control in adults with type 2 diabetes.

As of January 2014, Victoza^® has been commercially launched in 68 countries globally including the U.S., Canada, Japan, U.K., Germany, France, Italy, Denmark, Hungary, Russia, India, Brazil, Mexico, Argentina, Malaysia, and China, as well as a number of other countries, and will be available in other markets throughout 2014.

Indications and Usage:  

Victoza^® is an injectable prescription medicine that may improve blood sugar (glucose) in adults with type 2 diabetes when used along with diet and exercise.

Victoza^® (liraglutide [rDNA origin] injection) is not recommended as the first medication to treat diabetes. Victoza^® has not been studied in patients with history of inflammation of the pancreas (pancreatitis). Victoza^® is not a substitute for insulin and has not been studied in combination with prandial (mealtime) insulin. Victoza^® is not for people with type 1 diabetes or people with diabetic ketoacidosis. It is not known if Victoza^® is safe and effective in children. Victoza^® is not recommended for use in children.

Important Safety Information:  

In animal studies, Victoza^® caused thyroid tumors-including thyroid cancer-in some rats and mice. It is not known whether Victoza^® causes thyroid tumors or a type of thyroid cancer called medullary thyroid cancer (MTC) in people, which may be fatal if not detected and treated early. Do not use Victoza^® if you or any of your family members have a history of MTC or if you have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). While taking Victoza^®, tell your doctor if you get a lump or swelling in your neck, hoarseness, trouble swallowing, or shortness of breath. These may be symptoms of thyroid cancer. 

Do not use Victoza^® if you are allergic to liraglutide or any of the ingredients in Victoza^®.  Serious allergic reactions can happen with Victoza^®. If symptoms of serious allergic reactions occur, stop taking Victoza^® and seek medical attention. Pancreatitis may be severe and lead to death. Before taking Victoza^®, tell your doctor if you have had pancreatitis, gallstones, a history of alcoholism, or high blood triglyceride levels since these medical conditions make you more likely to get pancreatitis.

Stop taking Victoza^® and call your doctor right away if you have pain in your stomach area that is severe and will not go away, occurs with or without vomiting, or is felt going from your stomach area through to your back. These may be symptoms of pancreatitis.  

Before using Victoza^®, tell your doctor about all the medicines you take, especially sulfonylurea medicines or insulin, as taking them with Victoza^® may affect how each medicine works. If you use Victoza^® with insulin, you may give both injections in the same body area (for example, your stomach area), but not right next to each other.

Also tell your doctor if you have severe stomach problems such as slowed emptying of your stomach (gastroparesis) or problems with digesting food; have or have had kidney or liver problems; have any other medical conditions; or are pregnant or plan to become pregnant. Tell your doctor if you are breastfeeding or plan to breastfeed. It is unknown if Victoza^® will harm your unborn baby or if Victoza^® passes into your breast milk.

Your risk for getting hypoglycaemia, or low blood sugar, is higher if you take Victoza^® with another medicine that can cause low blood sugar, such as a sulfonylurea or insulin. The dose of your sulfonylurea medicine or insulin may need to be lowered while taking Victoza^® (liraglutide [rDNA origin] injection).

Victoza^® may cause nausea, vomiting, or diarrhea leading to dehydration, which may cause kidney failure. This can happen in people who have never had kidney problems before. Drinking plenty of fluids may reduce your chance of dehydration.

The most common side effects with Victoza^® include headache, nausea, and diarrhea. Nausea is most common when first starting Victoza^®, but decreases over time in most people. Immune system related reactions, including hives, were more common in people treated with Victoza^® compared to people treated with other diabetes drugs in medical studies.

Please click here for Prescribing Information and Medication Guide.

About Novo Nordisk 

Headquartered in Denmark, Novo Nordisk is a global healthcare company with more than 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 at Novo Nordisk Inc. Plainsboro, NJ. NN8022-1922, Oct 2013.     

2. Novo Nordisk A/S. Novo Nordisk files for regulatory approval of liraglutide 3 mg for the treatment of obesity. [Company Announcement]. http://www.novonordisk.com/include/asp/exe_news_attachment.asp?sAttachmentGUID=4182BBE8-6101-4AD9-802B-7B83302F8169. Accessed June 9, 2014.  

3. Victoza® [US prescribing information]. Plainsboro, NJ:Novo Nordisk Inc; 2013.Available at http://novo-pi.com/victoza.pdf. Accessed May 8, 2014. 

4. FDA. Guidance for Industry Developing Products for Weight Management. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM071612.pdf. Published 2007.  Accessed May 8, 2014. 

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

6 Flint A, Raben A, Ersbøll 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):781-92. 

7 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. 

© 2014 Novo Nordisk All rights reserved. 0514-00021426-1 June 2014 

SOURCE Novo Nordisk