NICE publishes positive Final Appraisal Determination for dapagliflozin

NICE recommends the use of dapagliflozin as a treatment option for adults with Type 2 diabetes as dual therapy in combination with metformin, and in combination with insulin with or without other oral antidiabetic drugs.(1) Currently in the UK, more than one million patients are on either metformin alone or insulin.(2)

The FAD recommends dapagliflozin to be used in combination with metformin instead of a sulphonylurea (SU) in certain patients. These are patients for whom an SU is not tolerated / contraindicated or are at significant risk of hypoglycaemia or its consequences. Furthermore, the addition of dapagliflozin to metformin may be preferable to a thiazolidinedione if further weight gain is a concern. This is in line with NICE guidance CG87 in relation to the use of dipeptidyl peptidase-4 (DPP-4) inhibitors in dual therapy with metformin.(3)

The FAD, which will form the basis of final NICE guidance, follows Marketing Authorisation issued on 14 November 2012 by the European Medicines Agency (EMA) and advice from the Scottish Medicines Consortium (SMC) on 14 January 2013.(4) The NICE recommendation means that adults with Type 2 diabetes who are not being managed on metformin alone or insulin will soon have access to this new, cost-effective oral once-daily, first-in-class  treatment.

Professor Clifford Bailey, Professor of Clinical Science at Aston University, UK, said, “Type 2 diabetes is a complex and progressive disease with the potential for a wide range of complications. Dapagliflozin is a once-daily tablet which is a new way to control blood glucose. It also has weight loss benefits.(5,6) It works in a novel way by removing excess glucose from the body in the urine. In this way, dapagliflozin removes calories from the body.(5) Dapagliflozin provides a new option for healthcare professionals and patients alike.”

Around 2.9 million people in the UK are living with diabetes,(7) nearly half of whom are uncontrolled on their current treatment regimens.(8) And a further 850,000 people have Type 2 diabetes but are unaware that they have the condition.(9) More than 80% of people with Type 2 diabetes are overweight.(10) Researchers have even coined a new term, diabesity, to acknowledge that these two conditions often coexist.(11) Weight gain adds to the burden of patients with Type 2 diabetes and increases the risk of cardiovascular disease.(9)

Gwen Hall, Diabetes Specialist Nurse, Portsmouth Community Diabetes Service, Primary Care Team, said, “I see a lot of people with diabetes who are worried about managing their blood glucose levels and who struggle to maintain a healthy weight. Some of our current therapies can carry an increased risk of hypoglycaemia, which is an additional concern for them. What people with diabetes would like is a treatment that not only effectively controls blood glucose levels but also has the secondary benefit of weight loss and, when used in combination with metformin, has a low risk of hypoglycaemia. Dapagliflozin appears to have these benefits.”

Dapagliflozin is the first in a new class of treatments called sodium-glucose cotransporter 2 (SGLT2) inhibitors,(12) which work independently of insulin.(5) Dapagliflozin works by reducing the amount of glucose reabsorbed in the kidney and as a result, in people with Type 2 diabetes, an increased amount of glucose is passed out of the body via the urine each day, along with the associated calories.

Unlike many other diabetes medications, dapagliflozin works in a novel way that is independent of insulin action. It therefore offers an alternative new approach for patients with Type 2 diabetes.(5)

Dr Malde Modhwadia, Chairman of the Trustees for the diabetes awareness charity, Silver Star Appeal, said, “We welcome NICE’s recommendation of dapagliflozin providing a new treatment option for patients living with Type 2 diabetes. Dapagliflozin works in a different way to existing treatments to lower blood glucose and may be beneficial for those many patients who also find losing weight a challenge.”

Dapagliflozin has been investigated in a comprehensive clinical development programme that assessed the safety and efficacy of the medicine as a once-daily oral therapy. These trials, which involved over 5,500 patients with Type 2 diabetes treated with dapagliflozin,(13) found that it effectively lowers HbA1c and maintains glycaemic control in adults with Type 2 diabetes for two years, has the additional secondary benefit of weight loss sustained for up to two years and is generally well tolerated.(5,6)

“We welcome NICE’s recommendation for dapagliflozin, the first medicine in this new class of treatment, which marks an important milestone in providing patients with Type 2 diabetes a cost-effective new treatment option. With the incidence of diabetes continuing to increase it is important for patients to have a wider choice of options so that the treatment can be tailored to their individual needs. Our Type 2 diabetes treatment portfolio has several different classes of medicine to help patients manage this complex condition,” commented Amadou Diarra, European VP and General Manager UK and Ireland, Bristol-Myers Squibb.

1. NICE Final Appraisal Determination: Dapagliflozin in combination therapy for treating type 2 diabetes. http://www.nice.org.uk
2. Patient Data, Cegedim Strategic Data UK Ltd, MAT Mar 2013
3. NICE short clinical guideline 87. Type 2 diabetes: newer agents for blood glucose control in type 2 diabetes Available at http://www.nice.org.uk/nicemedia/live/12165/44318/44318.pdf
4. Scottish Medicines Consortium (SMC) Advice on dapagliflozin. Available at: http://www.scottishmedicines.org.uk/SMC_Advice/Advice/799_12_dapagliflozin_Forxiga/dapagliflozin_Forxiga. Accessed May 2013
5. Bailey C et al. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomized, double-blind, placebo-controlled trial. Lancet. 2010;375(9733):2223-2233
6. Bailey CJ et al. Long-term efficacy of dapagliflozin as add-on to metformin (MET) in T2DM inadequately controlled with MET alone. Diabetes.2011;60(suppl 1):A271. Poster: American Diabetes Association (ADA): June 24-28, 2011
7. Diabetes UK State of the Nation England 2012. Available at: http://www.diabetes.org.uk/Documents/Reports/State-of-the-Nation-2012.pdf.  Accessed  May  2013
8. NHS Information Centre. Quality and Outcomes Framework. Online GP practice results database. Available at: http://www.qof.ic.nhs.uk . Accessed May 2013
9. Diabetes UK: Diabetes in the UK 2011/2012. Available at: http://www.diabetes.org.uk/documents/reports/diabetes-in-the-uk-2011-12.pdf.  Accessed  May  2013
10. Diabetes UK. Beware the silent assassin report. October 2008 http://www.diabetes.org.uk/Documents/Reports/Silent_assassin_press_report.pdf. Accessed May 2013
11. Diabesity in Practice. The journal for healthcare professionals managing people with coexisting diabetes and obesity. Available at: http://www.diabesityinpractice.co.uk. Accessed May 2013
12. FORXIGA Summary of Product Characteristics. Available at: http://www.medicines.org.uk/emc. Accessed May 2013
13. Ptaszynska A, Johnsson K, et al. Safety of dapagliflozin in clinical trials for T2DM. Poster 1011-P presented at the 72nd Scientific Sessions of the American Diabetes Association (ADA). 8–12 June 2012; Philadelphia, USA.