National Horizon Scanning Centre. Saxagliptin (BMS ) for type 2 diabetes. April 2008

Transcription

1 Saxagliptin (BMS ) for type 2 diabetes 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 Research Programme is part of the National Institute for Health Research

2 Saxagliptin (BMS ) for type 2 diabetes Target group Type 2 diabetes - in addition to, and as a substitute for, current glucose-lowering therapies. Technology description Saxagliptin (BMS ) is a reversible and competitive inhibitor of the protease dipeptidyl peptidase IV (DPP-IV), the enzyme that normally inactives glucagon-like peptide-1 (GLP-1). Since GLP-1 enhances insulin secretion in the presence of raised blood glucose levels, inhibiting DPP-IV activity will increase and prolong the action of GLP-1 by reducing its rate of inactivation in plasma. This mechanism of action leads to increased insulin biosynthesis and secretion (glucose dependent), to decreased glucagon, and a potentially improved beta-cell function. Saxagliptin is an oral agent, administered as a once daily dose ranging from mg. Innovation and/or advantages Saxagliptin has an earlier maximum effect of glucose clearance and insulin secretion compared to other DPP-IV inhibitors (vildagliptin, sitagliptin). Developer Bristol-Myers Squibb Pharmaceuticals and AstraZeneca. Availability, launch or marketing dates, and licensing plans: Saxagliptin is in phase III clinical s. NHS or Government priority area: This topic is relevant to the National Service Framework for Diabetes (2007). Relevant guidance NICE technology appraisal Inhaled insulin for the treatment of type 1 and type 2 diabetes Glitazones in the treatment of type 2 diabetes (Review of TA9 and TA21) The clinical effectiveness and cost effectiveness of long acting insulin analogues for diabetes NICE clinical guidelines in development Diabetes (type 2) - newer agents for blood glucose control. Expected February Type 2 diabetes: the management of type 2 diabetes (update). Expected May NICE clinical guideline Management of type 2 diabetes - managing blood glucose levels Other guidelines Clinical Knowledge Summaries. Diabetes type 2. Blood glucose management International Diabetes Federation. Global guideline for type 2 diabetes Clinical Standards Board for Scotland. Diabetes second edition SIGN. Management of diabetes Clinical need and burden of disease In England and Wales the prevalence of diabetes is between 3.5% and 5%, with around 1.6 million people diagnosed with diabetes. More than 85% of these people have type 2 diabetes. It is accepted that there are also many people with undiagnosed type 2 diabetes 4. 2

3 The prevalence of type 2 diabetes is at least 5 times higher amongst those from a black or ethnic minority background in the UK 11. Life expectancy is reduced by up to 10 years in people with diabetes 12. In ,267 deaths from non-insulin-dependent diabetes mellitus were recorded in England and Wales. Cardiovascular disease is the most common complication in Europeans with type 2 diabetes and the greatest cause of morbidity and premature death in this patient group, accounting for around 60% of all deaths from diabetes 13. Further diabetic complications include nephropathy, retinopathy, foot ulceration and erectile dysfunction. Existing comparators and treatments Insulin Oral Anti-diabetic drugs (alone or in combination): o Metformin: the only oral therapy shown to reduce deaths and prevent both microvascular and macro-vascular complications; o Sulfonylurea: an add on second-line therapy (e.g. glibenclamide, glipizide, chlorpropamide, tolbutamide, glimepiride); o Alpha-glucosidase inhibitors: acarbose, miglitol; o Thiazolidinedione (glitazones): rosiglitazone, pioglitazone; o DPP-4 inhibitors: sitagliptin, vildagliptin. Efficacy and safety Sponsor Status Location Design Participants in Follow-up Primary s Key results Adverse effects NCT ,15 : saxagliptin with metformin; Bristol-Myers Squibb Abstract USA, South America, Australia, Canada, Taiwan. Randomised, double-blind, n=720; adults; type 2 diabetes; metformin therapy; HbA1c 7.0% and 10.0%; fasting C-peptide 1ng/mL; body mass index 40kg/m 2. and metformin or placebo and metformin. 24 weeks Change in HbA1c. Postprandial assessments. HbA1c: decreased by between 0.71% and 0.83% vs. control (p<0.0001). Fasting plama glucose: decreased by between 16mg/dL and 24mg/dL vs. control (p<0.0001). Percentage with HbA1c <7%: 37%-44% vs. 17% control (p< ). No significant differences between groups. NCT : NCT : NCT : Sponsor Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb Status Unpublished Unpublished Ongoing Location USA, Russia, India, USA, Australia, Canada, USA Taiwan. South America, Taiwan. Design Participants in n=365; adults; type 2 n=460; adults; type 2 n=36; adults; type 2 3

4 diabetes; inadequate blood sugar control. or placebo. diabetes; treatment naive; HbA1c 7.0% and 10.0%; fasting C-peptide 1ng/mL; body mass index 40kg/m 2. or placebo. diabetes; treatments naive; HbA1c 6.0% and 8.0%; fasting C-peptide 1ng/mL; body mass index 40kg/m 2. 5mg or placebo. Follow-up 24 weeks - 12 weeks Primary Change in HbA1c. Change in HbA1c. Insulin secretion. s Compare each dose of saxagliptin vs placebo. Fasting plasma glucose, HbA1c <7%, postprandial glucose response. NCT : saxagliptin with thiazolidinedione; phase III. NCT : saxagliptin with metformin; Other measures of insulin secretion. NCT : Sponsor Bristol-Myers Squibb Bristol-Myers Squibb, AstraZeneca Bristol-Myers Squibb, AstraZeneca Status Unpublished Ongoing Ongoing Location USA, South America, Canada, India, Philippines. Europe (inc UK), Russia, Vietnam. Europe (no UK), Russia. Design Participants in n=555; adults; type 2 diabetes; thiazolidinedione (TZD) monotherapy; HbA1c 7.0% and 10.5%; fasting C-peptide 1ng/mL; body mass index 45kg/m 2. and TZD or placebo and TZD. active control. n=838; adults; type 2 diabetes; metformin monotherapy; HbA1c >6.5% and 10.0%. and metformin or suphonylurea and metformin. n=168; adults; type 2 diabetes; CrCl <50ml/min; HbA1c 7.0% and 11.0%. 2.5mg or placebo. Follow-up 24 weeks 52 weeks 52 weeks Primary Change in HbA1c. Change in HbA1c. Change in HbA1c. s Glucose tolerance test, fasting plasma glucose, glycemic response. Safety and tolerability, measurements of glucose metabolism. Safety and tolerability, measurements of glucose metabolism. NCT : saxagliptin with glyburide; NCT : saxagliptin with metformin; Sponsor Bristol-Myers Squibb Bristol-Myers Squibb Status Unpublished Unpublished Location USA, South America, Asia, South Africa. USA, South America, Europe (no UK), India, Philippines, Russia. Design Randomised, double-blind. Randomised, double-blind, active control. Participants in n=780; adults; type 2 diabetes; sulfonylurea monotherapy; inadequate blood sugar control. and glyburide n=1396; adults; type 2 diabetes; inadequate blood sugar control; no current treatment. Randomised to: 4

5 or placebo and glyburide. Arm A: saxagliptin 10mg or metformin; Arm B: saxagliptin 5mg or metformin; Arm C: saxagliptin 10mg or placebo; Active comparator: metformin or placebo. Follow-up 24 weeks 12 months Primary Change in HbA1c. Change in HbA1c. s Fasting plasma glucose, postpandrial glucose response, rescue or discontinued of treatment. Glycemic response, fasting plasma glucose, postprandial glucose response, rescue treatment. Estimated cost and cost impact The cost of saxagliptin is currently unknown. The costs of other licensed treatments are a : Drug name Dose 28 day cost Metformin 4 x 500mg /day 2.00 Gliclazide (Sulphonylurea) 2 x 80mg /day 1.32 Rosiglitazone 2 x 4mg /day Glimepiride(Sulphonylurea) 1 x 2mg/day 4.92 Metformin /Rosiglitazone 2 x 1g/4mg /day Sitagliptin 100mg /day Insulin glargine 40 IU/day Potential or intended impact speculative Patients Reduced morbidity Quicker, earlier or more accurate diagnosis or identification of disease Reduced mortality or increased survival Other: Improved quality of life for patients and/or carers None identified Services Increased use Service reorganisation required Staff or training required Decreased use from reduced morbility such as micro-and macro-vascular complications of type 2 diabetes Costs Increased unit cost compared to alternative New costs: References Other: Increased costs: more patients coming for treatment Savings: potential cost saving from decreased use of services None identified Increased costs: capital investment needed Other: 1 National Institute for Health and Clinical Excellence. Inhaled insulin for the treatment of type 1 and type 2 diabetes. Technology appraisal TA113. December National Institute for Health and Clinical Excellence. Glitazones in the treatment of type 2 diabetes (Review of TA9 and TA21). Technology appraisal TA63. August a British National Formulary March

6 3 National Institute for Health and Clinical Excellence. The clinical effectiveness and cost effectiveness of long acting insulin analogues for diabetes. Technology appraisal TA53. December National Institute for Health and Clinical Excellence. Diabetes (type 2) - newer agents for blood glucose control. Clinical guideline in development. Expected February National Institute for Health and Clinical Excellence. Type 2 diabetes: the management of type 2 diabetes (update). Clinical guideline in development. Expected May National Institute for Health and Clinical Excellence. Management of type 2 diabetes - managing blood glucose levels. Clinical guideline. September Clinical Knowledge Summaries. Diabetes type 2- blood glucose management. January International Diabetes Federation. Global guideline for type 2 diabetes Clinical Standards Board for Scotland. Diabetes second edition. October Scottish Intercollegiate Guidelines Network (SIGN). Management of diabetes. November Department of Health. Working together for better diabetes care. May Marshall SM, Flyvbjerg A. Prevention and early detection of vascular complications of diabetes. BMJ 2006;333: British Medical Association. Diabetes mellitus an update for healthcare professionals Clinicals.gov. Study assessing saxagliptin treatment in type 2 diabetic subjects who are not controlled with metformin alone. NCT Available at: (Accessed 07/03/2008). 15 DeFronzo RA, Hissa M, Blauwet MB et al. Saxagliptin added to metformin improves glycemic control in patients with type 2 diabetes. American Diabetes Association. 67 th Scientific Sessions Clinicals.gov. Study of BMS as monotherapy with titration in subjects with type 2 diabetes who are not controlled with diet and exercise. NCT Available at: (Accessed 07/03/2008). 17 Clinicals.gov. Saxagliptin treatment in subjects with type 2 diabetes who are not controlled with diet and exercise. NCT Available at: (Accessed 07/03/2008). 18 Clinicals.gov. A study assessing saxagliptin treatment in subjects with type 2 diabetes who are not controlled with diet and exercise. NCT Available at: (Accessed 07/03/2008). 19 Clinicals.gov. A study assessing saxagliptin treatment in type 2 diabetic subjects who are not controlled with TZD therapy alone. NCT Available at: (Accessed 07/03/2008). 20 Clinicals.gov. 52-week add-on to metformin comparison of saxagliptin and sulphonylurea. NCT Available at: (Accessed 07/03/2008). 21 Clinicals.gov. Treatment effect of saxagliptin compared with placebo in patients with type 2 diabetes and renal impairment. NCT Available at: (Accessed 07/03/2008). 22 Clinicals.gov. A study of saxagliptin in subjects with type 2 diabetes who have inadequate blood sugar control with sulfonylureas. NCT Available at: (Accessed 07/03/2008). 23 Clinicals.gov. A phase 3 study of BMS in combination with metformin in subjects with type 2 diabetes who are not controlled with diet and exercise. NCT Available at: (Accessed 07/03/2008). The National Institute for Health Research Research Programme is funded by the Department of Health. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health The, Department of Public Health and Epidemiology University of Birmingham, Edgbaston, Birmingham, B15 2TT, England Tel: +44 (0) Fax +44 (0)