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# Premixed insulin dosing in actual practice

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Many have troubles choosing the proper insulin type and dosing for their patients.. Here is a quick presentation that introduce you to different studies in that matter.
This presentation is intended for healthcare prfessionals

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### Premixed insulin dosing in actual practice

1. 1. The Community Pharmacist’s Role in Diabetes Management 4 Premixed insulin dosing in actual practice Anas Bahnassi PhD RPh
2. 2. Conventional premixed insulin formulations The community pharmacist role in diabetes management Insulin Peaks Duration 30 minutes 2 to 4 hours 22 to 24 hours Humalog mix 75/25 or 50/50 Lispro + N Humulin mix 70/30 or 50/50 R +N Novolog mix 70/30 Aspart + N Novolin mix 70/30 R+N 11/15/2013 Onset of action 2
3. 3. Premixed insulin dosing The community pharmacist role in diabetes management Step1:First calculate the total daily starting requirement of insulin BodyWeight For a 60kg patient total daily dose =30 units 2 Step 2:Then divide this dose into 3 equal parts 10+10+10 Step 3:Give 2 parts in the morning and 1 part in the evening Morning=20U Evening=10 U 3 11/15/2013
4. 4. Premixed insulin dosing The community pharmacist role in diabetes management Step1:First calculate the total daily starting requirement of insulin BodyWeight For a 60kg patient total daily dose =30 units 2 Another approach is to provide 50% of the dose In the morning and 50% at bedtime Other doses of 55:45 to 60:40 where morning doses exceed evening doses are preferable 4 11/15/2013 Jung, C. H., et al. Diabetic Medicine (2013).
5. 5. Dose titration The community pharmacist role in diabetes management You can increase or decrease the dose of pre-mixed insulin by 10 % If the patients is using, 1-10 units………….….+/- 1 unit 11-20 units……………+/- 2 units 21-30 units……………+/- 3 units 31-40 units……………+/- 4 units………………….. 5 11/15/2013
6. 6. Advantages of premixed insulin The community pharmacist role in diabetes management • Easy to administer for the physician • Easy to fill and inject by the patient • Provides both basal and bolus coverage with fewer number of injections. 6 11/15/2013
7. 7. Disadvantages of premixed insulin The community pharmacist role in diabetes management • No dose flexibility • Increasing or decreasing the dose of one component if the premix will result in corresponding change to the other component. 7 11/15/2013
8. 8. Twice-daily split mixed regimen 160 Insulin (mU/mL) The community pharmacist role in diabetes management 140 120 100 80 60 40 IGT 20 Type 2 diabetes 0 0800 1200 1600 2000 2400 0400 Nocturnal hypoglycemia 8 11/15/2013
9. 9. Three-times-daily split mixed regimen 160 Insulin (mU/mL) The community pharmacist role in diabetes management 140 120 100 80 60 IGT 40 Type 2 diabetes 20 0 0800 1200 1600 2000 2400 0400 9 11/15/2013
10. 10. The dual-release insulin concept The community pharmacist role in diabetes management • Physiological insulin profile: - meal-related peak • - basal component Rapid-acting insulin analogue together with a basal insulin analogue provide physiological insulin replacement Physiological insulin profile Rapid insulin analogue • Premix analogues mimic physiological insulin secretion Protamine crystallised insulin aspart Premix analogue 10 11/15/2013 Profiles are schematic
11. 11. The community pharmacist role in diabetes management Glucose infusion rate (mg/kg/min) Human vs. Analogue insulin mix Faster onset of rapid-acting part and similar duration of the basal component compared with premixed human insulin 12 10 8 Dose = 0.3 U/kg n = 24 healthy volunteers Humalog mix 30% Premixed human insulin 6 4 2 0 0 240 480 720 Time (min) 960 1200 1400 11 11/15/2013 Weyer C, et al. Diabetes Care 1997;10:1612–1614
12. 12. Improved postprandial blood glucose after 3 months Premixed analogue insulin * Premixed human insulin * Blood glucose (mmol/l) The community pharmacist role in diabetes management 12 * 10 * 8 n = 294 type 1 and type 2 patients 6 * p < 0.05 0 Pre- Post- Pre- Post- Pre- Post- Breakfast Lunch Dinner Boehm B, et al. Diabet Med 2002;19:393–399 11/15/2013 Bedtime 02.00 h 12
13. 13. Post-prandial blood glucose Mean prandial glucose increment (mmol/l) The community pharmacist role in diabetes management 3 p < 0.02 2.5 2 1.5 1 0.5 0 Analogue Premix (n = 128) Boehm B, et al. Diabet Med 2002;19:393–399 11/15/2013 human insulin Premix (n = 141) 13
14. 14. Major hypoglycaemia episodes Premixed Analogue Human insulin Premix Patients with at least one major episode (%) The community pharmacist role in diabetes management n = 125 type 2 diabetes patients p = 0.04 12 p = NS 10 8 6 4 3 11 8 2 events events events 0 1st year 2nd year Year of study 14 11/15/2013 Boehm B, et al. Eur J Int Med 2004;15:496–502
15. 15. Nocturnal hypoglycemia p = 0.02 Human insulin mix 30 n = 160 type 2 diabetes patients CBGM Readings <3.5 mmol/l (%) The community pharmacist role in diabetes management Analog mix 30 9 19% 8 7 6 5 p = 0.067 4 7.8 6.3 3 2 1 2.9 3.3 0 Day time (06.00 to midnight) Night time (midnight to 06.00) 15 11/15/2013 McNally P, et al. Diabetologia 2004;47(Suppl 1):A327
16. 16. Efficacy or safety of pre- or post-meal dosing of Analogue mix 30 After postprandial injection (64.6 ± 29.2 U) 240 220 Mean plasma glucose (mg/dl) The community pharmacist role in diabetes management After preprandial injection (63.0 ± 28.9 U) n = 93 type 2 diabetes patients 200 180 160 140 120 100 -15 60 120 180 240 Time (minutes) 16 11/15/2013 Warren ML, et al. Diabetes Res Clin Pract 2004;66:23–29
17. 17. Glucose excursions n = 61 type 2 diabetes patients Blood glucose excursion0– 5 h (mmol/l/h) The community pharmacist role in diabetes management p < 0.001 21 20 p < 0.05 –17% –10% 19 18 17 16 15 14 13 0 Aspart Mix® 30 Lispro Mix 25TM Mean injection dose 0.4 U/kg Premixed human insulin 17 11/15/2013 Hermansen K, et al. Diabetes Care 2002;25:883–888
18. 18. AUC of premixed aspart insulin vs. long acting glargine insulin Total daily injection dose 0.5 U/kg NovoMix® 30 Glargine 400 Plasma insulin (pM) The community pharmacist role in diabetes management n = 12 type 2 diabetes patients Aspart Mix 30 or glargine PI AUC0-24 h; p < 0.01 350 300 250 200 150 100 50 0 -1 4 9 14 Aspart Mix 30 19 24 Time (h) 18 11/15/2013 Luzio S, et al. Diabetes 2004;53(Suppl. 2):A136
19. 19. Once-daily analong mix effect on blood glucose over 24 hours Once-daily phase of the 1-2-3 Study Baseline Analog mix OD (16 weeks) 14 12 Blood Glucose (mmol/l) The community pharmacist role in diabetes management • 10 8 6 4 Before After Breakfast 11/15/2013 Before After Lunch Before After Dinner Bed 3am time 19
20. 20. Once-daily analogue mix effect on HbA1c in type 2 diabetes Reduction in HbA1c(%) The community pharmacist role in diabetes management 11/15/2013 8.6% Baseline values 8.2% 9.5% 8.6% 0 n=71 -0.5 -1 -1.5 n=120 (11 weeks) (12 weeks) n=46 n=100 (12 weeks) (16 weeks) -2 Suwanwalaikorn Diabetologia 2004;48(suppl 1):A308. Lund et al Diabetes 2005;56(suppl 1):A126. 20 Kilo et al J Diabetes Complications 2003;17(6):307-13. Garber et al Diab Obes Metab 2005, in press
21. 21. The community pharmacist role in diabetes management Phase 1 OD Pre-dinner x 16 week Start with 12 U at dinner HbA1c≤ 6.5% End of Study If HbA1c> 6.5%, go to BID, d/c secretagogues Phase 2 BID Phase 3 TID 11/15/2013 Pre-breakfast & dinner x 16 week Add 3 U at breakfast and titrate HbA1c≤ 6.5% End of Study If HbA1C> 6.5%, go to TID TID x 16 week Add 3 U at lunch and titrate Titrate according to schedule every 3 days n = 100 type 2 DM  12 months with HbA1c  7.5  10%,  2 OADs or  1 OAD plus basal insulin OD (max 60 U) 21 Garber A, et al. Diabetes, Obesity and Metabolism 2006;8(1):58-66 The 1-2-3 study: Investigating Asprat Mix OD, BID and TID
22. 22. Sum-up The community pharmacist role in diabetes management • Analogue Premixed insulin vs. premixed human insulin 30/70 – – – – improves postprandial blood glucose (Boehm et al 2002) reduces risk of hypoglycaemia (Boehm et al 2004, McNally et al) dosing immediately before or after meal (Warren et al) reduces triglycerides (Schmoelzer et al) • Analogue Premixed insulin BID vs. glargine OD – 34% higher glucose lowering effect in equal daily dose clamp (Luzio et al) – 50% more patients reach HbA1c targets (Raskin et al) – reduces PPG (Raskin et al) – comparable FPG reduction (Raskin et al) – equal risk of major hypoglycaemia and more minor hypoglycaemia (Kann et al) 22 11/15/2013
23. 23. The Community Pharmacist’s Role in Diabetes Management CE program for pharmacists Anas Bahnassi PhD CDM CDE abahnassi@gmail.com http://www.twitter.com/abpharm http://www.facebook.com/pharmaprof http://www.linkedin.com/in/abahnassi