Premixed insulin dosing in actual practice
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Premixed insulin dosing in actual practice Anas Bahnassi PhD RPh The Community Pharmacist’s Role in Diabetes Management 4
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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
Transcript of Premixed insulin dosing in actual practice
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
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Anas Bahnassi PhD CDM CDE
