Liraglutide (Victoza) in combination with basal insulin for type 2 diabetes

Transcription

1 Liraglutide (Victoza) in combination with basal insulin for type 2 diabetes May 2011 This technology summary is based on information available at the time of research and a limited literature search. It is not intended to be a definitive statement on the safety, efficacy or effectiveness of the health technology covered and should not be used for commercial purposes. The National Horizon Scanning Centre Research Programme is part of the National Institute for Health Research

2 Liraglutide (Victoza) in combination with basal insulin for type 2 diabetes Target group Type 2 diabetes mellitus third line, in combination with basal insulin, after failure to achieve glycaemic control with liraglutide and metformin. Technology description Liraglutide (Victoza, NN2211) is a long-acting, stable analogue of the natural hormone glucagon-like peptide-1. It is intended to be used in combination with basal insulin and an oral antidiabetic agent such as metformin for the third line treatment (triple therapy) of adults with type 2 diabetes mellitus not achieving adequate glycaemic control with liraglutide and metformin. Liraglutide is administered subcutaneously at 1.2mg or 1.8mg daily. Liraglutide is licensed for the treatment of type 2 diabetes mellitus to achieve glycaemic control in combination with: Metformin or a sulphonylurea in patients with insufficient glycaemic control despite maximum tolerated dose of metformin or sulphonylurea monotherapy. In combination with metformin and a sulphonylurea, or metformin and a thiazolidinedione, in patients with insufficient glycaemic control despite dual therapy. Liraglutide is also in phase III trials for the treatment of obesity. Very common adverse events (AEs) associated with liraglutide when used in combination with metformin, metformin and glimepiride, and metformin and rosaglitazone, are nausea and diarrhoea. Vomiting is a very common AE when liraglutide is used with metformin and glimepiride, headache is a very common AE when liraglutide is used with metformin, and hypoglycaemia is a very common AE when liraglutide is used with glimepiride. Innovation and/or advantages If licensed, the combination of liraglutide and basal insulin would offer an additional treatment step for those patients with inadequate glycaemic control with liraglutide and oral antidiabetic agents. Developer Novo Nordisk. Availability, launch or marketing dates, and licensing plans In phase III clinical trials. NHS or Government priority area This topic is relevant to The National Service Framework for Children, Young People and Maternity Services (2004) and The National Service Framework for Diabetes (2007). Relevant guidance NICE technology appraisal in development. Prolonged release exenatide for the second line (dual therapy) or third line (triple therapy) treatment of type 2 diabetes. Expected February NICE technology appraisal. Liraglutide for the treatment of type 2 diabetes

3 NICE technology appraisal. Guidance on the use of long-acting insulin analogues for the treatment of diabetes-insulin glargine NICE clinical guideline. Type 2 diabetes: the management of type 2 diabetes SIGN. Management of diabetes: A national clinical guideline Clinical Knowledge Summaries. Insulin therapy in type 2 diabetes Clinical Knowledge Summaries. Diabetes type Clinical Knowledge Summaries. Diabetes type 2: Managing glucose control National Collaborating Centre for Chronic Conditions. Type 2 diabetes: national 9 clinical guideline for management in primary and secondary care (update) International Diabetes Federation. Global guideline for type 2 diabetes Clinical need and burden of disease The prevalence of diabetes in the UK is increasing, but not accurately known, and varies with factors including age, ethnic group and social deprivation. In England the prevalence of diabetes (diagnosed and undiagnosed) in adults is estimated to be 7.4%, which equates to almost 3,010,000 people above the age of 16 years 11,a. In Wales, the prevalence is estimated to be 9%, equating to around 219,000 people above the age of 16 years 12,b. More than 85% of people with diabetes are expected to have type 2 diabetes 3 and in 2009 it was estimated that there were 821,800 adults with diabetes who were not diagnosed 13. Prevalence of diabetes among adults in the UK is estimated to rise to 8.5% in 2020, and 9.5% by In England in 2005, there were 26,300 deaths in people aged 20 to 79 years that were attributable to diabetes (11.6% of all deaths in this age group) 14. However, clinical coding practice means that only a minority of deaths in people with diabetes from causes that can be associated with the disease have diabetes identified as the primary cause of death 13. Life expectancy is reduced by up to 10 years in this patient group 15. Cardiovascular disease is a common complication of type 2 diabetes and is a significant cause of morbidity and premature death, accounting for around 60% of all deaths from diabetes 16. Other long-term complications associated with diabetes include: nephropathy, retinopathy and neuropathy, leading respectively to renal failure, reduced vision or blindness and foot ulceration and amputation. Existing comparators and treatments Current treatment options include 3,8 : Oral anti-diabetes drugs (alone or in combination): Metformin. Sulfonylureas: gliclazide, glibenclamide, glipizide, tolbutamide, glimepiride. Alpha-glucosidase inhibitors: acarbose. Thiazolidinediones (glitazones): pioglitazone. DPP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin. Injectable drugs: Exenatide (twice daily SC). Liraglutide (once daily SC). Insulin (human or analogue) a Uncertainty limits 5.3%-10.8%. b Uncertainty limits 6.9%-11.9%. 3

4 Current practice is that treatment should aim to achieve a target glycated haemoglobin (HbA1c) level of 6.5% for the first 2 treatment steps, or 7.5% if further treatment steps are required or where there is severe risk of hypoglycaemia. Efficacy and safety Trial Sponsor Status Source of information Location Design Participants and schedule Follow-up Primary outcome Secondary outcomes Expected reporting date NCT , NN , ; liraglutide, insulin detemir and metformin vs liraglutide and metformin; phase III. Novo Nordisk. Complete but unpublished. Trial registry 17, manufacturer. EU (inc UK), US, Canada and Puerto Rico. Randomised, active-controlled. n=987; adults; type 2 diabetes mellitus; insulin naïve; 3 months stable treatment regimen containing metformin and/or a sulfonylurea. All patients receive liragltuide (1.8mg daily SC) and metformin ( 1,500mg daily). At week 12, patients with HbA1c 7% remained on liraglutide and metformin; patients with HbA1c 7% were randomised to receive liragltuide (1.8mg daily SC), insulin detemir (individually adjusted dose SC) and metformin ( 1,500mg daily), or liragltuide (1.8mg daily SC) and metformin ( 1,500mg daily). Active treatment period 26 weeks (plus 26 week extension). Change in HbA1c from baseline. Fasting plasma glucose; 7-point plasma glucose profile; fasting insulin, C-peptide and proinsulin; lipids; body weight; adverse events; hypoglycaemic events. June Estimated cost and cost impact The cost of liraglutide is for 2 x 3mL pens (6mg/mL, 1.2mg daily as maintenance therapy) 18 ; this is not expected to change as a result of this new indication. Insulin detemir costs for 5 x 3mL pens (100 units/ml, 40 units daily c ) 18. The cost of other selected treatments for type 2 diabetes are summarised below 18 : Drug Dose Unit cost Pioglitazone 15mg-45mg once daily 28 x 15mg: x 30mg: x 45mg: Metformin 1.5-2g daily 84 x 500mg: 1.61 Sitagliptin 100mg once daily 28 x 100mg: Exenatide 5µg - 10µg twice daily 60 x 5µg: Claimed or potential impact speculative Patients Reduced mortality or increased length of survival delete as appropriate Other: Reduction in associated morbidity or Improved quality of life for patients and/or carers Quicker, earlier or more accurate diagnosis or identification of disease None identified c WHO defined daily dose for insulin. 4

5 Services Increased use Costs Service organisation: increased requirements for monitoring glycaemic control with insulin therapy. Staff requirements Decreased use Other: None identified Increased unit cost compared to Increased costs: more patients Increased costs: capital alternative coming for treatment investment needed New costs: additional therapy. Savings: Other: Other issues Clinical uncertainty or other research question identified: None identified References 1 National Institute for Health and Clinical Excellence. Prolonged release exenatide for the second-line (dual therapy) or third-line (triple therapy) treatment of type 2 diabetes. Technology appraisal in development. Expected February National Institute for Health and Clinical Excellence. Liraglutide for the treatment of type 2 diabetes. Technology appraisal TA203. London: NICE; October National Institute for Health and Clinical Excellence. Guidance on the use of long-acting insulin analogues for the treatment of diabetes - Insulin glargine. Technology appraisal TA53. London: NICE; December National Institute for Health and Clinical Excellence. Type 2 diabetes: the management of type 2 diabetes. Clinical guideline CG87. London: NICE; May Scottish Intercollegiate Guidelines Network. Management of diabetes; A national clinical guideline. Edinburgh: SIGN; March NHS Clinical Knowledge Summaries. Insulin therapy in type 2 diabetes. November NHS Clinical Knowledge Summaries. Diabetes type 2. December NHS Clinical Knowledge Summaries. Diabetes type 2: managing glucose control. December National Collaborating Centre for Chronic Conditions. Type 2 diabetes: national clinical guideline for management in primary and secondary care (update). London: Royal College of Physicians; International Diabetes Federation. Global guideline for type 2 diabetes. Brussels: IDF; Yorkshire and Humber Public Health Observatory. Diabetes Prevalence Model for England Accessed 8 April Yorkshire and Humber Public Health Observatory. Diabetes Prevalence Model for Wales. Accessed 8 April Yorkshire and Humber Public Health Observatory. Diabetes prevalence model: key findings for England. YHPHO: June Yorkshire and Humber Public Health Observatory. Diabetes attributable deaths: estimating the excess deaths among people with diabetes. YHPHO: May Marshall S and Flyvbjerg A. Prevention and early detection of vascular complications of diabetes. British Medical Journal 2006;333: British Medical Association. Diabetes mellitus: an update for healthcare professionals. London: BMA; Clinicaltrials.gov. The effect of insulin detemir in combination with liraglutide and metformin compared to liraglutide and metformin in subjects with type 2 diabetes. Accessed 8 April British Medical Association and Royal Pharmaceutical Society of Great Britain. British National Formulary. London: BMJ Group and RPS Publishing; March

6 The National Institute for Health Research National Horizon Scanning Centre Research Programme is funded by the Department of Health. The views expressed in this publication are not necessarily those of the NHS, the NIHR or the Department of Health The National Horizon Scanning Centre, Department of Public Health and Epidemiology University of Birmingham, 90 Vincent Drive, Edgbaston, Birmingham, B15 2SP, England Tel: +44 (0) Fax +44 (0)