The trial named LEADER™ (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) aims to assess and confirm the cardiovascular safety of the company's new once-daily human GLP-1 analogue Victoza® and potentially show the ability of Victoza® to improve cardiovascular outcomes. The trial also satisfies the new FDA guideline for type 2 diabetes treatments.
Because of the scientific opportunity this trial presents, the protocol has been designed in close collaboration with an international expert Steering Committee as well as US and EU regulatory authorities, and with assistance from the Population Health Research Institute (PHRI) at McMaster University, Canada. Furthermore, an independent Data Monitoring Committee (DMC) will monitor progress of the trial and ensure that it meets the highest standards of ethics and patient safety.
"There is a well-established association between cardiovascular disease (CVD) and type 2 diabetes," said Dr John Buse, Chief of Endocrinology and Director of the Diabetes Care Centre at the University of North Carolina School of Medicine, and Chairman of the LEADER™ Steering Committee. "In fact, CVD ranks as the major cause of death in diabetes, accounting for more than 50% of all diabetes fatalities. As a result there is a serious unmet need for further long-term studies to help reduce the risk of CVD in patients with type 2 diabetes."
The vast majority of people with type 2 diabetes suffer from a range of co-morbidities, such as obesity,(1) hypertension1 and dyslipidaemia.(2) The high prevalence of co-morbidities in combination with hyperglycaemia are the likely contributors to the increased risk of cardiovascular disease complications in adults with type 2 diabetes.(3) Yet, only 10% of diabetes patients have good control of both blood glucose, hypertension and dyslipidaemia.(4)
In addition to the underlying link between CVD and type 2 diabetes, some older type 2 diabetes treatments may be associated with increases in CVD risk.(5) Evidence of this association prompted regulatory authorities to require additional studies of type 2 diabetes treatments in order to ascertain that all newer drugs do not unacceptably increase CVD risk.(5)
Previous data from the LEAD™ (Liraglutide Effect and Action in Diabetes) trials has shown Victoza® not only to improve glucose control (HbA1c -1.0–1.6%)(6,7,8,9,10,11) but also to induce weight loss of 2–3 kg on average (6,7,8,9,10) lower blood pressure by 2–6 mmHg (6,7,8,9,10,11) and potentially reduce lipids and other cardiovascular risk markers such as total cholesterol, LDL, TG, FFA, BNP, CRP(12) in patients with type 2 diabetes.
About LEADER™
LEADER™ (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) is a long-term, multicentre, international, randomised, double-blind, placebo-controlled, phase 3b trial which will include around 9,000 patients over a five-year period.
The trial will compare liraglutide added to standard of care with standard of care alone in people with type 2 diabetes.
GLP-1 analogue Victoza® (liraglutide)
Once-daily Victoza® is the first human GLP-1 (Glucagon-Like Peptide-1) analogue developed for the treatment of type 2 diabetes. Victoza® lowers blood glucose by stimulating the release of insulin and lowering of glucagon secretion when blood sugar levels are high and also by slowing gastric emptying.(13) Victoza® also reduces body weight and body fat mass through mechanisms involving reduced hunger and lowered energy intake.(14)
Victoza® is a once-daily injection taken any time of day independent of meals.(14)
Novo Nordisk received marketing authorisation for Victoza® on 30 June 2009 in the EU, 20 January 2010 in Japan and 25 January 2010 in the US. It has been launched in the US, UK, Germany and several other European markets.
About Novo Nordisk
Headquartered in Denmark, Novo Nordisk is a global healthcare company with 87 years of innovation and leadership in diabetes care. The company also has leading positions within haemophilia care, growth hormone therapy and hormone replacement therapy. For more information, visit novonordisk.com.
1. Agency for Healthcare Research and Quality. Prevalence of obesity and other chronic health conditions among diabetic adults in the US community population, 2001. Medical Expenditure Panel Survey. 2004. Available at URL: http://www.meps.ahrq.gov/mepsweb/data_files/publications/st34/stat34.pdf. Last accessed March 2010.
2. Jacobs et al. Prevalence and control of dyslipidemia among persons with diabetes in the United States. Diabetes Res Clin Pract. 2005;70:263–269.
3. Saydah, S et al. Poor control of risk factors for vascular disease among adults with diabetes. JAMA. 2004;291(3):335-342.
4. Cheung B et al. Diabetes prevalence and therapeutic target achievement in the United States, 1999 to 2006. Am J Med. 2009;122:443-53.
5. Food and Drug Administration. Guidance for Industry: Diabetes Mellitus — Evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes. US Department of Health and Human Services. December 2008.
6. Marre M et al. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with Type 2 diabetes (LEAD-1 SU). Diabetic Medicine. 2009;26: 268–278.
7. Nauck M et al. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin, in type 2 diabetes. The LEAD (Liraglutide Effect and Action in Diabetes)-2 study. Diabetes Care. 2009;32:84–90.
8. Garber A et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet. 2009; 373(9662):473-481.
9. Zinman B et al. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiazolidinedione in patients with type 2 diabetes mellitus (LEAD-4 Met+TZD). Diabetes Care. 2009;32:1224-1230.
10. Russell-Jones D et al. Liraglutide vs insulin glargine and placebo in combination with metformin and sulphonylurea therapy in type 2 diabetes mellitus: a randomised controlled trial (LEAD-5 met+SU). Diabetologia. 2009;52(10):2046-55.
11. Buse J, et al. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet. 2009;374(9683):39-47.
12. Plutzky J, Garber A, Toft A et al. Meta analysis demonstrates that liraglutide, a once-daily human GLP-1 analogue, significantly reduces lipids and other markers of cardiovascular risk in type 2 diabetes. Diabetologia. 2009; in press.
13. Knudsen et al. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem 2000;43:1664–9.
14. Victoza® Summary of Product Characteristics (SPC) is available at www.ema.europa.eu. Victoza has market authorisation in the EU and US.
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