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Clinical presentation of insulin detemir

Clinical presentation of insulin detemir. February 2006. Structure of insulin detemir. Insulin detemir: mode of prolonging action . Self association (hexameric) Fatty acid side chains bind to albumin in injection depot Albumin binding in circulation. Protracted absorption.

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Clinical presentation of insulin detemir

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  1. Clinical presentationof insulin detemir February 2006

  2. Structure of insulin detemir

  3. Insulin detemir: mode of prolonging action • Self association (hexameric) • Fatty acid side chains bind to albumin in injection depot • Albumin binding in circulation Protracted absorption ‘Buffering’ effect and minor contribution to protraction

  4. Insulin detemir 0.2 U/kg Insulin detemir 0.3 U/kg Insulin detemir 0.4 U/kg 2.0 1.5 Glucose infusion rate (mg/kg/min) 1.0 0.5 0 0 24 20 16 12 8 4 Time since injection (hours) PD profile of insulin detemir: subjects with type 1 diabetes Adapted from J. Plank et al. Diabetes Care 2005;28(5):1107-12

  5. Clamp 1 Clamp 2 Clamp 3 Clamp 4 8.0 8.0 8.0 NPH insulin Insulin glargine Insulin detemir 6.0 6.0 6.0 GIR mg/(kg.min) 4.0 4.0 4.0 2.0 2.0 2.0 0 0 0 0 6 12 18 24 0 6 12 18 24 0 6 12 18 24 Time (hours) Time (hours) Time (hours) Less variable time-action profile than NPH insulin or insulin glargine Glucose infusion rate profiles following four non-consecutive injections of identical doses (0.4 U/kg, thigh) in three patients Adapted from T. Heise et al. Diabetes 2004:1614-20

  6. *p < 0.05 Insulin detemir NPH insulin 5 * * * * * * * * * 4 Studies in type 2 diabetes 3 SD of self-measured FBG/FPG (mmol/l) 2 1 0 Vague Hermansen Robertson Haak Pieber Home Kølendorf Rašlová Hermansen Russell-Jones Consistent reduction in blood glucose variability

  7. Lower HbA1c than NPH in a meta-analysis of clinical trials Endpoint data from 6 trials comparing insulin detemir with NPH insulin in basal-bolus therapy in: type 1 diabetes (Russell-Jones 2004, Hermansen 2004, Home 2004, Pieber 2005) & type 2 diabetes (Haak 2005, Raslova 2004) A.J. Garber, H. Kim, E. Draeger. Diabetologia 2004;47(Suppl. 1):A58

  8. *p < 0.05 for insulin detemir vs. NPH 1.2 1 * * * * * * * * * * * * * * 0.8 Relative Risk (IDet/NPH) 0.6 0.4 0.2 0 HbA1c: Detemir NPH 7.73 7.60 7.53 7.67 7.65 7.75 7.78 8.02 7.55 8.30 7.88 7.49 7.63 6.58 7.67 7.64 7.59 7.73 7.94 7.93 7.55 8.41 8.11 7.51 7.48 6.46 Haak 2004 Home 2004 Home 2004 Pieber 2003 Pieber 2003 Vague 2003 Standl 2002 Raslova 2004 De Leeuw 2004 Robertson 2004 Kolendorf 2004 Hermansen 2004 Hermansen 2006 Consistent improvement in balance between control & hypoglycaemia Russell-Jones 2004 Overall hypoglycaemia Nocturnal hypoglycaemia

  9. Consistent reduction in weight gain 3 Levemir + OADtreat-to-target study Insulin detemir 2.5 *p<0.05, insulin detemir vs. NPH insulin NPH insulin 2 * * * * * * * * * * * * 1.5 1 Weight change (kg) 0.5 0 Studies in type 2 diabetes -0.5 Vague Standl Home## Haak Home# Pieber‡ Pieber† Rašlová De Leeuw Russell-Jones -1 Hermansen Hermansen †IDet (am+predinner); ‡IDet (am+bed); #IDet (12 hourly); ##IDet (am + bed)

  10. Insulin detemir provides: • A prolonged and reproducible time-action profile • Less variability in comparison to NPH insulin • Improved glycaemic control compared with NPH insulin • A risk reduction for nocturnal hypoglycaemia compared with NPH insulin • Less weight gain

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