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Taspoglutide for Type 2 Diabetes Mellitus – Add-On Therapy August

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Taspoglutide for Type 2 Diabetes Mellitus – Add-On Therapy August Taspoglutide for type 2 diabetes mellitus – add-on therapy August 2010 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 August 2010 Taspoglutide for type 2 diabetes mellitus – add-on therapy Target group • Type 2 diabetes mellitus - in combination with metformin, or metformin and a sulphonylurea or a thiazolidinedione. Technology description Taspoglutide is a long-acting glucagon like peptide (GLP-1) analogue which binds specifically with glucagon-like-peptide 1 receptors (GLP-1R) found on pancreatic β cells. In addition to the short term effects of enhancing glucose-induced insulin secretion, continuous GLP-1R activation also increases insulin synthesis, β cell proliferation and gluconeogenesis. Taspoglutide will be self-administered by subcutaneous (SC) injection and is currently being trialled at a dose of 10-20mg once weekly. Innovation and/or advantages If licensed taspoglutide may provide a longer-acting treatment option for patients with hyperglycaemia uncontrolled by current medication. Taspoglutide may also be useful in treating early phase diabetes for patients who still have pancreatic β cell function. Developer Roche Products. Availability, launch or marketing dates, and licensing plans In phase III trials. NHS or Government priority area This topic is relevant to the National Service Framework for Diabetes (2007). Relevant guidance • NICE technology appraisal in development. Liraglutide for the treatment of type 2 diabetes. Expected October 20101. • NICE short clinical guideline. Type 2 diabetes: newer agents for blood glucose control in type 2 diabetes. 20092. 3 • NICE clinical guideline. Type 2 diabetes: the management of type 2 diabetes. 2008 . • Clinical Knowledge Summaries. NHS Clinical Knowledge Summary. Diabetes – type 2. Version 2.5. 2010 4. 5 • International Diabetes Federation. Global guideline for type 2 diabetes. 2005 . Clinical need and burden of disease The prevalence of diabetes in the UK is increasing, but is not accurately known, and varies with factors including the mix of ethnic groups and degree of social deprivation. In England and Wales the prevalence is estimated to be between 3.5% and 5%, with around 1.6 million people diagnosed, and more than 85% of adults with diabetes having type 2 diabetes3. It is accepted that a number of people with type 2 diabetes remain undiagnosed. An estimated 4.2% of deaths in men and 7.7% of deaths in women in the UK can be attributed to diabetes. However, these are likely to be underestimates as death registrations for vascular events, such as stroke and myocardial infarction, frequently 2 August 2010 under record the underlying causative disease3. Life expectancy is reduced by up to 10 years in people with diabetes6. Cardiovascular disease is the most common complication in Europeans with type 2 diabetes and is a significant cause of morbidity and premature death in this patient group, accounting for around 60% of all deaths7. Other long-term complications associated with the condition 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: • Oral anti-diabetes drugs (alone or in combination) • Metformin. • Sulfonylureas: gliclazide, glibenclamide, glipizide, tolbutamide, glimepiride. • Alpha-glucosidase inhibitors: acarbose. • Thiazolidinediones (glitazones): rosiglitazone, pioglitazone. • DPP-4 inhibitors: sitagliptin, vildagliptin, saxagliptin. • Injectable drugs • Exenatide (twice daily SC). • Liraglutide (once daily SC). • Insulin (human or analogue). Efficacy and safety Trial NCT00423501; metformin with taspoglutide or placebo; phase II. Sponsor Hoffman-La Roche. Status Published. Source of Publication8. information Location EU, USA and other countries. Design Randomised, placebo-controlled. Participants and n=306; adults; type 2 diabetes inadequately controlled with metformin. schedule Randomised to taspoglutide 5, 10 or 20mg once weekly, 10 or 20mg once every two weeks, or placebo. Subjects enrolled were on stable doses of metformin ≥ 1500mg/day, which they received throughout study. Follow-up 8 week active treatment period and 4 week follow up. Primary Change in baseline HbA1c at week 8. outcome Secondary Fasting plasma glucose (FPG), body weight, glucagon, fasting insulin, C-peptide outcomes and lipid profile. Key results At 8 weeks, reduction in HbA1c for all taspoglutide groups (baseline mean 7.9) statistically significantly greater than placebo (-1.0, -1.2, -1.2, -0.9 and -1.0 vs - 0.2, all p<0.0001). At 8 weeks, reduction in body weight statistically significantly greater than placebo for 10mg and 20mg once weekly, and 20mg once every two weekly taspoglutide groups (-2.1, -2.8 and -1.9 vs -0.8kg, all p<0.01). Adverse effects Most common AE: dose-dependent, mild to moderate nausea (22% of patients in (AEs) 20mg taspoglutide arm). Other AEs included mild to moderate gastrointestinal disturbance and injection site reactions. Hypoglycaemia incidence low across all arms. Trial NCT01051011; NCT00909597; NCT00717457; metformin with taspoglutide vs taspoglutide vs exenatide; taspoglutide or insulin pioglitazone; phase III. phase III. 3 August 2010 glargine; phase III. Sponsor Hoffman-La Roche. Hoffman-La Roche. Hoffman-La Roche. Status Ongoing. Ongoing. Ongoing. Source of Trial registry9. Trial registry10. Trial registry11. information Location Hong Kong. EU (inc UK), USA, EU (inc UK), USA, Canada and other Canada and other countries. countries. Design Randomised, open-label, Randomised, active- Randomised, active- active-controlled. controlled. controlled. Participants and n= 570 (planned); adults; n= 648 (planned); adults; n=990 (planned); adults schedule type 2 diabetes type 2 diabetes type 2 diabetes inadequately controlled inadequately controlled inadequately controlled with metformin and with sulfonylurea alone or with metformin, sulfonylurea combination in combination thiazolidinedione or a therapy (metformin (metformin combination (metformin ≥1500mg/day). ≥1500mg/day). ≥1500mg/day). Randomised to Randomised to Randomised to taspoglutide 10mg once taspoglutide 10mg once taspoglutide 10mg once weekly, taspoglutide weekly, taspoglutide weekly, taspoglutide 20mg once weekly or 10mg once weekly (for 4 10mg once weekly (for 4 insulin glargine titrated to weeks) followed by 20mg weeks) followed by 20mg FPG. once weekly, or once weekly, or exenatide All arms receive currently pioglitazone 30mg once 5mg twice daily (for 4 prescribed metformin daily (4 weeks) followed weeks) followed by 10mg throughout study. by 45mg once daily. twice daily. Follow-up 24 weeks with option to 24 week treatment period. 24 week treatment period. continue assigned treatment for additional 28 weeks. Primary HbA1c at week 24. HbA1c at week 24. HbA1c at week 24. outcome Secondary FPG, incidence of Target HbA1c at week 24, Body weight, target outcomes hypoglycaemia, body 52 and 104; body weight. HbA1c, β cell function weight, lipid profile, and relative change in glucagon, C-peptide and glucose, insulin, C- insulin. peptide and glucagon values. Expected Expected completion June Expected completion July Expected completion Apr reporting date 2012. 2012. 2012. 4 August 2010 Trial NCT00744367; NCT00754988; NCT00755287; metformin and taspoglutide with metformin with pioglitazone with metformin and placebo vs taspoglutide or insulin taspoglutide or placebo; sitagliptin with metformin glargine; phase III. phase III. and placebo; phase III. Sponsor Hoffman-La Roche. Hoffman-La Roche. Hoffman-La Roche. Status Ongoing. Ongoing. Ongoing. Source of Trial registry12. Trial registry13. Trial registry14. information Location EU, USA, Canada and EU, USA, Canada and EU, USA, Canada and other countries. other countries. other countries. Design Randomised, placebo- Randomised, active and Randomised, active controlled. placebo-controlled. controlled. Participants and n= 330 (planned); adults; n= 630 (planned); adults; n= 990 (planned); adults; schedule type 2 diabetes type 2 diabetes type 2 diabetes inadequately controlled inadequately controlled inadequately controlled with metformin plus with metformin. with metformin plus a pioglitazone. Randomised to sulphonylurea Randomised to taspoglutide 10mg once (metformin taspoglutide 10mg weekly with metformin ≥1500mg/day). weekly, taspoglutide and oral placebo, Randomised to 10mg once weekly (4 taspoglutide 10mg once taspoglutide 10mg once weeks) then 20mg once weekly (4 weeks) weekly, taspoglutide weekly, or placebo. followed by 20mg once 10mg once weekly (4 All arms to receive weekly with metformin weeks) then taspoglutide pioglitazone (>30mg/day) and oral placebo, 20mg once weekly, or and metformin sitagliptin 100mg once insulin glargine (starting (>1500mg/day) daily, SC placebo once dose of 10 IU daily). throughout study. weekly and metformin, or All arms receive SC placebo once weekly prescribed metformin with metformin and oral dose throughout study. placebo. Follow-up Treatment period 52 Study treatment period of Study treatment period of weeks. 24 weeks with extension 24 weeks with extension to 52 weeks. Follow up 2 to 52 weeks. Follow
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