1 / 21

Insulin detemir: more predictability

Insulin detemir: more predictability . David Russell-Jones United Kingdom. Tuesday. Wednesday. Monday. Variability. CGMS plots for one patient on three successive days of once-daily NPH insulin. 20.0. 15.0. 10.0. Glucose concentration (mmol/l) . 5.0. 0.0. -5.0. 12:00 am. 8:00 pm.

elisha
Download Presentation

Insulin detemir: more predictability

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Insulin detemir: more predictability David Russell-Jones United Kingdom

  2. Tuesday Wednesday Monday Variability

  3. CGMS plots for one patient on three successive days of once-daily NPH insulin 20.0 15.0 10.0 Glucose concentration (mmol/l) 5.0 0.0 -5.0 12:00 am 8:00 pm 12:00 am 4:00 pm 12:00 pm 4:00 am 8:00 am Time

  4. Variability: types and measures Types of variability: • Between subject • Affects dose titration • Within subject • Affects glycaemic control throughout treatment Ways to measure variability • Standard deviation • Co-efficient of variation (CV) Standard deviation x 100 = Mean

  5. 70 60 50 40 CV (%) 30 20 10 0 Variability is particularly marked with basal insulin Pharmacodynamic variability2Glucose AUC (0–24hrs) Pharmacokinetic variability1 70 Insulin Cmax Insulin Tmax 60 50 40 CV (%) 30 20 10 0 NPH insulin Ultralente Lente NPH insulin Adapted from 1. Galloway JA et al. Diabetes Care 1981;4:366-76. 2. Scholtz HE et al. Diabetologia 1999;42(Suppl 1):A235.

  6. PK/PD study of profiles of insulin detemir, NPH insulin and insulin glargine Randomisation Insulin glargine x 4 0.4 U/kg n = 16 Insulin detemir x 4 0.4 U/kg n = 18 NPH insulin x 4 0.4 U/kg n = 17 Euglycaemic clamp, parallel group, randomised, double-blind study with four identical doses given to each subject at four different dosing days Heise T et al. Diabetes 2004;53:1614-20.

  7. Insulin detemir has lower PK variability than other insulins 40 NPH insulin 35 Insulin glargine 30 Insulin detemir 25 CV (%) 20 15 10 5 0 Ins AUC (0-12) Cmax PK parameters were not statistically analysed Heise T et al. Diabetes 2004;53:1614-20.

  8. 7 7 7 7 7 7 7 7 7 6 6 6 6 6 6 6 6 6 5 5 5 5 5 5 5 5 5 4 4 4 4 4 4 4 4 4 3 3 3 3 3 3 3 3 3 2 2 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 0 0 0 0 0 0 0 0 0 0 8 16 0 0 0 0 0 0 0 8 8 8 8 8 8 8 16 16 16 16 16 16 16 24 24 24 24 24 24 24 24 24 0 8 16 Variability in basal insulin action NPH insulin insulin glargine insulin detemir Glucose infusion rate (mg/kg/min) Time (hours) Heise T et al. Diabetes 2004;53:1614-20.

  9. 7 7 7 7 7 7 7 7 7 6 6 6 6 6 6 6 6 6 5 5 5 5 5 5 5 5 5 4 4 4 4 4 4 4 4 4 3 3 3 3 3 3 3 3 3 2 2 2 2 2 2 2 2 2 1 1 1 1 1 1 1 1 1 0 0 0 0 0 0 0 0 0 0 8 16 24 0 0 0 0 0 0 0 0 8 8 8 8 8 8 8 8 16 16 16 16 16 16 16 16 24 24 24 24 24 24 24 24 Variability in basal insulin action NPH insulin insulin glargine insulin detemir Glucose infusion rate (mg/kg/min) Time (hours) Heise T et al. Diabetes 2004;53:1614-20.

  10. Insulin detemir has a lower variability of action than other insulins p < 0.001 80 70 p < 0.001 60 50 (Glucose infusion rate AUC0–24) CV (%) 40 30 20 10 0 NPH insulin Insulin Insulin glargine detemir Heise T et al. Diabetes 2004;53:1614-20.

  11. Insulin detemir (Levemir®): clinical study • 6-month multicentre, open, randomised 2:1, parallel trial in 747 subjects with type 1 diabetes • 92 sites in 11 countries Bedtime insulin detemir+ mealtime soluble (regular) human insulin (n=491) CGMS subset (n = 99) 3 weeks’ run in Bedtime NPH insulin + mealtime soluble (regular) human insulin (n = 256) CGMS subset (n = 39) Randomisation 6 months Russell-Jones D et al. Clinical Therapeutics 2004;26:724-36.

  12. Fasting glucose is significantly improved with insulin detemir relative to NPH insulin Baseline HbA1c = 8.35% Russell-Jones D et al. Clinical Therapeutics 2004;26:724-36 *self-monitored. FBG, fasting blood glucose

  13. Insulin detemir: consistent nocturnal profile Mean glucose Insulin detemir 10 180 NPH insulin 9 162 8 144 (mmol/l) (mg/dl) 7 126 6 108 0 0 20.00 22.00 0.00 02.00 04.00 06.00 08.00 Time CGMS profiles Russell-Jones D et al. Clinical Therapeutics 2004;26:724-36

  14. Example profiles: interstitial glucose fluctuations from the mean Glucose 25 450 Patient 1 –NPH insulin 20 360 15 270 (mg/dl) (mmol/l) 10 180 5 90 0 0 Glucose 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:00 02:00 04:00 06:00 450 25 Patient 2 – Insulin detemir 360 20 270 15 (mmol/l) (mg/dl) 180 10 90 5 0 06:00 08:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 00:00 02:00 04:00 06:00 CGMS profiles Russell-Jones D et al. Clinical Therapeutics 2004;26:724-36 Time

  15. Insulin detemir: reduced fluctuation in blood glucose Mean fluctuationfrom individual average bloodglucose Daytime Nocturnal 3 54 Insulin detemir 2 36 NPH insulin 1 18 (mg/dl) (mmol/l) 0 0 –1 –18 –2 –36 6 10 14 18 22 2 6 Time (hours) CGMS profiles Russell-Jones D et al. Clinical Therapeutics 2004;26:724-36

  16. Glucose fluctuation is significantly less variable with insulin detemir ANOVA of fluctuations (mmol/l x h) over 24 hours (Data taken from 72-hour glucose profiles after 5 months of treatment) Russell-Jones D et al. Clinical Therapeutics 2004;26:724-36

  17. Insulin detemir: phase III clinical studies

  18. Within-subject variability of self-monitored pre-breakfast glucose conc. all phase 3 studies **p<0.001; *p<0.05, insulin detemir vs. NPH Insulin detemir NPH insulin 5 ** ** ** ** ** ** ** * * 4 Studies in type 2 diabetes 3 SD of self-measured FBG/FPG (mmol/l) 2 1 0 Haak Vague Pieber Home Rašlová Robertson Kølendorf Hermansen Russell-Jones

  19. Summary • Insulin detemir gives: • significantly lower fasting plasma glucose • significantly lower within-subject variation of fasting blood glucose • less fluctuation in blood glucose level acrossthe day and night More predictable glycaemic control

  20. Potential benefits of More predictable glycaemic control • More confident patients? • Reduced hypoglycaemia? • Reduced weight gain?

  21. Monday Predictability Tuesday Wednesday

More Related