Phase 3a liraglutide 3 mg trial demonstrated significant weight loss and improved cardiovascular risk factors in adults with obesity and type 2 diabetes compared with placebo

Novo Nordisk's picture
Printer-friendly versionPrinter-friendly versionPDF versionPDF version

Chicago, US, 21 June 2014 Today, new data from the phase 3a SCALE™ Diabetes trial were presented at the International Congress of Endocrinology (ICE) and the Endocrine Society’s meeting (ENDO), investigating the effect of liraglutide 3 mg in adults with obesity and type 2 diabetes or who were overweight with type 2 diabetes. Data demonstrated that, at 56 weeks, in addition to clinically meaningful weight loss, treatment with liraglutide 3 mg provided statistically significantly greater improvements in risk factors for cardiovascular (CV) disease, compared with placebo, in combination with diet and physical activity.

All treatment groups followed a reduced-calorie diet and increased physical activity programme. At 56 weeks of treatment, the SCALE™ Diabetes trial demonstrated that adults treated with liraglutide 3 mg achieved significantly greater mean weight loss of 5.9% compared with 2.0% with placebo (p<0.0001). The 3.0 mg dose also produced more weight loss than liraglutide 1.8 mg (4.6%, p=0.0024). Waist circumference was also significantly reduced with both liraglutide 3 mg (–6.0 cm) and liraglutide 1.8 mg

(–4.9 cm), compared with placebo (–2.8 cm, p=0.0004).

"Cardiovascular disease is a major concern in people with obesity and type 2 diabetes," said Dr. Ralph DeFronzo, Deputy Director of the Texas Diabetes Institute, San Antonio, and a SCALE™ Diabetes trial investigator. "The results from the SCALE™ Diabetes trial indicate that treatment with liraglutide 3 mg may lead to improvements across a number of cardiovascular disease risk factors, including cholesterol and blood pressure, which may be especially important for this patient population."

A moderate weight loss of 5 to 10% has been shown to reduce risk factors for CV disease in people with obesity.In the SCALE™ Diabetes trial, liraglutide 3 mg and 1.8 mg significantly reduced systolic blood pressure by 3.0 and 3.1 mmHg respectively, compared with 0.4 mm Hg with placebo (p<0.05). No significant difference between treatments was observed in diastolic blood pressure. Compared with baseline, liraglutide 3 mg significantly improved total cholesterol (–4%) and fasting lipid levels, including very low-density lipoproteins, high-density lipoproteins and triglycerides (–13%, +3% and –14%, respectively, p<0.05). Liraglutide 1.8 mg had no significant effect on cholesterol or lipid levels.

Liraglutide 3 mg and 1.8 mg significantly improved levels of the inflammatory marker C-reactive protein (CRP) by –27% and –25% compared with placebo (p=0.0002). CRP is elevated in people with obesity and is a good predictor of CV disease. Compared with placebo, liraglutide 3 mg additionally improved CV risk factors, including the blood clot risk factor plasminogen activator inhibitor-1 (–24%, p=0.0004) and the urinary albumin/creatinine ratio (–20%, p=0.0086),which is a common marker for chronic kidney disease.

The most frequently reported side effects were gastrointestinal disorders (driven by nausea and diarrhoea), 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 occurring in more than 5% of people treated with liraglutide 3 mg included hypoglycaemia, 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%).

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 US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), respectively, 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. These applications are under review.

Liraglutide is currently available in the US and other countries at lower doses under the brand name Victoza® for treatment of adults with type 2 diabetes mellitus to improve blood glucose control. Victoza® is not approved for weight management.

FDA guidance 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 favourably to weight-management medications.7 The FDA requested the inclusion of liraglutide 1.8 mg (Victoza®) 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-1,8 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. The dual actions of liraglutide 3 mg on both appetite and blood glucose regulation (for adults with prediabetes 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, randomised, placebo-controlled, double-blind, phase 3a clinical trial involving 846 adults with obesity or who are overweight and have type 2 diabetes. It was designed to demonstrate clinically meaningful weight loss with liraglutide 3 mg in this population. It is one of four trials in the SCALE™ clinical development programme, which encompassed more than 5,000 participants who are obese with or without comorbidities or overweight with comorbidities.

About Victoza®

Victoza® (liraglutide) is a human glucagon-like peptide-1 (GLP-1) analogue with an amino acid sequence 97% similar to endogenous human GLP-1. Like natural GLP-1, Victoza® works by stimulating the beta cells to release insulin and suppressing glucagon secretion from the alpha cells only when blood sugar levels are high. Due to this glucose-dependent mechanism of action, Victoza® is associated with a low rate of hypoglycaemia. In addition, Victoza® reduces body weight and body-fat mass through mechanisms involving reduced appetite and lowered food intake.

Victoza® was launched in the EU in 2009 and is commercially available in more than 68 countries globally. Currently, there are more than 830,000 patients receiving Victoza® worldwide. In the US, Victoza® was approved on 25 January 2010 as an adjunct to diet and exercise to improve blood sugar control in adults with type 2 diabetes.

Hypoglycaemia has primarily been observed when Victoza® is combined with a sulfonylurea.

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.

Further information

Media:

   

Katrine Sperling

+45 4442 6718

krsp@novonordisk.com

Sharon Corbitt (US)

+1 609 578 9974

shct@novonordisk.com

Investors:

   

Kasper Roseeuw Poulsen

+45 3079 4303

krop@novonordisk.com

Jannick Lindegaard Denholt

+45 3079 8519

jlis@novonordisk.com

Daniel Bohsen

+45 3079 6376

dabo@novonordisk.com

Frank Daniel Mersebach (US)

+1 609 235 8567

fdni@novonordisk.com

References

1. DeFronzo RA, Bergenstal RM, Bode B, et al. Effects of Liraglutide 3.0 Mg and 1.8 Mg on Body Weight and Cardiometabolic Risk Factors in Overweight and Obese Adults with Type 2 Diabetes Mellitus (T2DM): The Scale Diabetes Randomized, Double-Blind, Placebo-Controlled, 56-Week Trial. Abstract number SAT-0930. International Congress of Endocrinology & The Endocrine Society, Chicago, IL. 2014

2. Dengo AL, Dennis EA, Orr JS, et al. Arterial destiffening with weight loss in overweight and obese middle-aged and older adults. Hypertension. 2010;55:855-861

3. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56:320-328

4. Visser M, Bouter LM, McQuillan GM, et al. Elevated C-reactive protein levels in overweight and obese adults. Jama. 1999;282:2131-2135

5. Eddy AA, Fogo AB. Plasminogen activator inhibitor-1 in chronic kidney disease: evidence and mechanisms of action. Journal of the American Society of Nephrology : JASN. 2006;17:2999-3012

6. Novo Nordisk data on file.

7. FDA. Guidance for Industry - Developing Products for Weight Management. 2007. Available at: http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071612.pdf [Last accessed 5 June 2014].

8. 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;43:1664-1669

9. Flint A, Raben A, Ersboll AK, et al. The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity. Int J Obes Relat Metab Disord. 2001;25:781-792

10. van Can J, Sloth B, Jensen CB, et al. Effects of the once-daily GLP-1 analog liraglutide on gastric emptying, glycemic parameters, appetite and energy metabolism in obese, non-diabetic adults. Int J Obes (Lond). 2013

News Source : Phase 3a liraglutide 3 mg trial demonstrated significant weight loss and improved cardiovascular risk factors in adults with obesity and type 2 diabetes compared with placebo
Copy this html code to your website/blog to embed this press release.