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

1. The Community Pharmacist’s Role in
Diabetes Management
4
Premixed insulin dosing
in actual practice
Anas Bahnassi PhD RPh

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
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Onset of
action
2

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
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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
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Jung, C. H., et al. Diabetic Medicine (2013).

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
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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
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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
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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
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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
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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
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Profiles are schematic

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
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Weyer C, et al. Diabetes Care 1997;10:1612–1614

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
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Bedtime
02.00 h
12

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
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human insulin Premix
(n = 141)
13

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
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Boehm B, et al. Eur J Int Med 2004;15:496–502

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)
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McNally P, et al. Diabetologia 2004;47(Suppl 1):A327

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
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Warren ML, et al. Diabetes Res Clin Pract 2004;66:23–29

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
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Hermansen K, et al. Diabetes Care 2002;25:883–888

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
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Luzio S, et al. Diabetes 2004;53(Suppl. 2):A136

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
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Before After
Lunch
Before
After
Dinner
Bed 3am
time
19

20. Once-daily analogue mix effect on
HbA1c in type 2 diabetes
Reduction in HbA1c(%)
The community pharmacist role in diabetes management
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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. 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
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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. 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)
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23. The Community Pharmacist’s Role in Diabetes Management
CE program for pharmacists
Anas Bahnassi PhD CDM CDE
abahnassi@gmail.com
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