Post on 07-May-2015
description
Premixed insulin dosing in actual practice
Anas Bahnassi PhD RPh
The Community Pharmacist’s Role in Diabetes Management 4
Conventional premixed insulin formulations
Insulin Onset of action
Peaks Duration
Humalog mix 75/25 or 50/50
Lispro + N
30 minutes
2 to 4 hours
22 to 24 hours
Humulin mix 70/30 or 50/50 R +N
Novolog mix 70/30
Aspart + N
Novolin mix 70/30
R+N 11/15/2013
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Step 3:Give 2 parts in the morning and 1 part in the evening
Morning=20U Evening=10 U
Premixed insulin dosing
Step1:First calculate the total daily starting requirement of insulin
2
Weight Body For a 60kg patient total daily dose =30 units
Step 2:Then divide this dose into 3 equal parts 10+10+10
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Premixed insulin dosing
Step1:First calculate the total daily starting requirement of insulin
2
Weight Body For a 60kg patient total daily dose =30 units
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
Jung, C. H., et al. Diabetic Medicine (2013). 11/15/2013
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Dose titration
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…………………..
You can increase or decrease the dose of pre-mixed insulin by 10 %
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Advantages of premixed insulin
• 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.
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Disadvantages of premixed insulin
• No dose flexibility
• Increasing or decreasing the dose of one component if the premix will result in corresponding change to the other component.
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160
140
120
100
80
60
40
20
0
Insu
lin (m
U/m
L)
0800 1200 1600 2000 2400 0400
IGT
Type 2 diabetes
Twice-daily split mixed regimen
Nocturnal hypoglycemia
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160
140
120
100
80
60
40
20
0
Insu
lin (m
U/m
L)
0800 1200 1600 2000 2400 0400
IGT
Type 2 diabetes
Three-times-daily split mixed regimen
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The dual-release insulin concept
• Physiological insulin profile:
- meal-related peak
- basal component
• Rapid-acting insulin
analogue together with
a basal insulin analogue
provide physiological insulin
replacement
• Premix analogues mimic
physiological insulin secretion
Physiological insulin profile
Protamine crystallised insulin aspart
Rapid insulin analogue
Premix analogue
Profiles are schematic 11/15/2013
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Human vs. Analogue insulin mix
Weyer C, et al. Diabetes Care 1997;10:1612–1614
Glu
cose
infu
sio
n r
ate
(m
g/k
g/m
in) 12
8
6
4
2
0
10
0 240 480 720 960 1200 1400
Premixed human insulin
Humalog mix 30%
Dose = 0.3 U/kg n = 24 healthy volunteers
Time (min)
Faster onset of rapid-acting part and similar duration of the basal component compared with premixed human insulin
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Boehm B, et al. Diabet Med 2002;19:393–399
*
Blo
od
glu
cose
(m
mo
l/l)
*
0 Pre-
10
12
Post-
8
6
*
*
Lunch
Pre- Post-
Breakfast
Pre- Post-
Dinner
Bedtime 02.00 h
Premixed analogue insulin
Premixed human insulin
* p < 0.05
n = 294 type 1 and type 2 patients
Improved postprandial blood glucose after 3 months
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0
0.5
1
1.5
2
2.5
3
Analogue Premix human insulin Premix
Me
an p
ran
dia
l glu
cose
in
cre
me
nt
(mm
ol/
l) p < 0.02
(n = 128) (n = 141)
Boehm B, et al. Diabet Med 2002;19:393–399
Post-prandial blood glucose
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Boehm B, et al. Eur J Int Med 2004;15:496–502
Major hypoglycaemia episodes
0
2
4
6
8
10
12
1st year 2nd year Year of study
Pat
ien
ts w
ith
at
leas
t o
ne
maj
or
ep
iso
de
(%)
p = NS
p = 0.04
3
events
11
events
8
events
n = 125 type 2 diabetes patients
Human insulin Premix
Premixed Analogue
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Nocturnal hypoglycemia
McNally P, et al. Diabetologia 2004;47(Suppl 1):A327
CB
GM
R
ead
ings
<3
.5 m
mo
l/l (
%)
Day time (06.00 to midnight)
Night time (midnight to 06.00)
Human insulin mix 30
Analog mix 30
n = 160 type 2 diabetes patients
p = 0.067
p = 0.02
19%
2.9
6.3
3.3
7.8
0
1
2
3
4
5
6
7
8
9
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Warren ML, et al. Diabetes Res Clin Pract 2004;66:23–29
Efficacy or safety of pre- or post-meal dosing of Analogue mix 30
After preprandial injection (63.0 ± 28.9 U)
After postprandial injection (64.6 ± 29.2 U)
Mea
n p
lasm
a gl
uco
se (
mg
/dl)
-15 60 120 180 240
120
100
140
160
180
200
220
240
n = 93 type 2 diabetes patients
Time (minutes)
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Hermansen K, et al. Diabetes Care 2002;25:883–888
Blo
od
glu
cose
exc
urs
ion
0–
5 h
(m
mo
l/l/
h)
p < 0.05
–10%
p < 0.001
–17%
0
13
14
15
16
17
18
19
20
21
Lispro Mix 25TM Aspart Mix® 30 Premixed human insulin
n = 61 type 2 diabetes patients
Mean injection dose 0.4 U/kg
Glucose excursions
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Luzio S, et al. Diabetes 2004;53(Suppl. 2):A136
Aspart Mix 30 or glargine
Aspart Mix 30
0
50
100
150
200
250
300
350
400
-1 4 9 14 19 24
Time (h)
Pla
sma
insu
lin (
pM
) NovoMix® 30
Glargine
PI AUC0-24 h; p < 0.01
n = 12 type 2 diabetes patients
Total daily injection dose 0.5 U/kg
AUC of premixed aspart insulin vs. long acting glargine insulin
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Once-daily analong mix effect on blood glucose over 24 hours
• Once-daily phase of the 1-2-3 Study
Blo
od
Glu
cose
(m
mo
l/l)
Lunch
Baseline
Analog mix OD (16 weeks)
4
14
Before After Bed time
3am Breakfast
Before After Before After
Dinner
6
8
10
12
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Once-daily analogue mix effect on HbA1c in type 2 diabetes
Suwanwalaikorn Diabetologia 2004;48(suppl 1):A308. Lund et al Diabetes 2005;56(suppl 1):A126. Kilo et al J Diabetes Complications 2003;17(6):307-13. Garber et al Diab Obes Metab 2005, in press
Re
du
ctio
n in
Hb
A1
c(%
)
-2
-1.5
-1
-0.5
0
n=71
n=46 n=100 n=120
8.6% 9.5% 8.2% 8.6%
(11 weeks)
(12 weeks)
(12 weeks) (16 weeks)
Baseline values
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The 1-2-3 study: Investigating Asprat Mix OD, BID and TID
Pre-dinner x 16 week Start with 12 U at dinner
HbA1c≤ 6.5% OD
Phase 1 End of
Study
If HbA1c> 6.5%, go to BID, d/c secretagogues
Pre-breakfast & dinner x 16 week Add 3 U at breakfast and titrate
BID
Phase 2 End of
Study
HbA1c≤ 6.5%
If HbA1C> 6.5%, go to TID
TID x 16 week Add 3 U at lunch and titrate TID
Phase 3
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) G
arb
er A
, et
al.
Dia
bet
es, O
bes
ity
an
d M
eta
bo
lism
20
06
;8(1
):5
8-6
6
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Sum-up
• 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)
• 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)
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The Community Pharmacist’s Role in Diabetes Management CE program for pharmacists
abahnassi@gmail.com
http://www.twitter.com/abpharm
http://www.facebook.com/pharmaprof
http://www.linkedin.com/in/abahnassi
Anas Bahnassi PhD CDM CDE