Therapeutic options for
patients sub-optimally
controlled on human
premix insulin
Speaker name and affiliation
UKHMG00716(1) October 2015
Meetings developed by Eli Lilly & Company Ltd in conjunction with SB Communications
Group. Eli Lilly & Company Ltd fully funded these meetings
Company Confidential © 2012 Eli Lilly and Company
Company Confidential © 2012 Eli Lilly and Company
Prescribing information is available on the last slide.
Some practical factors to consider when
changing a patient’s insulin regimen
HbA1c
Language
SMBG
Body
Weight
Motivation
Dose
adjustment
Age
The factors that
determine a
patient’s regimen
Key
will befactors
individual
and vary from
patient to patient.
Carb
awareness
Cognitive
ability
Injection
freq/
device
Hypos
Comorbidity
Occupation
Lifestyle
SMBG=self-monitoring of blood glucose.
Company Confidential © 2012 Eli Lilly and Company
Diet &
exercise
What options exist for
those with suboptimal
control on biphasic
human insulin 30/70?
Some commonly considered options*
Options for people
with suboptimal control
on Human premix
30/70
Move to an
analogue premix
with a similar ratio of
basal/prandial
coverage?
Consider using
basal plus bolus
insulin?
Move to a premixed
preparation with
greater prandial
coverage?
*Assuming Humulin® M3 has been optimised appropriately.
Company Confidential © 2012 Eli Lilly and Company
Company Confidential © 2012 Eli Lilly and Company
4
Moving to an analogue
premix with a similar ratio
of basal/prandial coverage
Evidence from randomised trials
and considerations
Comparison of human insulin 30/70
with insulin lispro 25/75
 Six-month, randomised, open-label, two-period crossover study.
 Included 89 individuals with type 2 diabetes.
 Each insulin administered twice daily.
 Conclusion:
In comparison to treatment with human insulin
30/70, twice daily administration of analogue premix
25/75 resulted in improved postprandial glycemic
control, similar overall glycemic control, and the
convenience of dosing immediately before meals
Roach P et al (1999) Diabetes Care 22: 1258–61
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6
Initiating pre-mixed insulin therapy:
NICE guidance*
Consider premixed preparations that
include short-acting insulin
analogues, rather than premixed
preparations that include shortacting human insulin preparations, if:
The person prefers
injecting insulin
immediately before a
meal.
Hypoglycaemia is a
problem.
Blood glucose levels
rise markedly after
meals.
*Note: When insulin is initiated, NICE recommends beginning with human neutral protamine Hagedorn insulin injected at bed-time
or twice daily according to need.
NICE (2009) Type 2 Diabetes. The Management of Type 2 Diabetes. NICE Clinical Guideline 87. Available at: http://www.nice.org.uk/CG87 (accessed (3.10.2013)
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7
Summary
 Switching from human insulin 30/70 to an analogue premixed insulin
with a similar ratio:
– May not yield overall improvement in HbA1c.
– May be useful if PPG is a concern or hypoglycaemia is a problem.
– May be useful if a person wishes to “inject and eat”.
PPG=postprandial plasma glucose.
Company Confidential © 2012 Eli Lilly and Company
Company Confidential © 2012 Eli Lilly and Company
8
Summary
Options for people
with suboptimal
control on Human
premix 30/70
Move to an
analogue premix
with a similar ratio of
basal/prandial
coverage?
Company Confidential © 2012 Eli Lilly and Company
Company Confidential © 2012 Eli Lilly and Company
Consider using
basal plus bolus
insulin?
Move to a premixed
preparation with
greater prandial
coverage?
9
Moving to using basal and
bolus insulin
Evidence from randomised trials
and considerations
Premixed insulin compared with
basal–bolus: The GINGER study
 A 52-week, open-label, randomised, multinational, multicentre trial
that included 310 subjects with type 2 diabetes on premixed insulin
(human or analogue – either 25/75 or 30/70), with or without
metformin.
 Participants randomised to a basal–bolus regimen (with glargine and
glulisine) or twice-daily premixed insulin (either human 30/70, or
aspart 30/70).
GINGER=Glulisine in Combination with Insulin Glargine in an Intensified Insulin Regimen.
Fritsche A et al (2010) Diabetes Obes Metab 12: 115–23
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11
Main results of the GINGER study
At study end:
 Number of overall
hypoglycaemic events per year
were higher in the premix
group, but the difference was
not significant (P=0.2385).
 Weight gain was significantly
greater in the basal–bolus
group (+3.6 vs. +2.2 kg;
P=0.0073).
GINGER=Glulisine in Combination with Insulin Glargine in an Intensified Insulin Regimen.
Fritsche A et al (2010) Diabetes Obes Metab 12: 115–23
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12
In “Real World” Practice, Is Basal–Bolus Always
The Gold Standard?
 High injection frequency can lead to poor adherence, causing
inadequate glycaemic control in insulin treated type 2 patients.1
 Noncompliance in insulin treated type 2 patients is associated with
increased all-cause mortality.2
 Many people with type 2 diabetes on basal–bolus therapy have
suboptimal glycaemic control. In one large study*, almost two thirds of
people failed to achieve HbA1c ≤7% (≤53 mmol/mol).3
*This was a multinational, 52-week, open-label, parallel-group, non-inferiority, treat-to-target trial, designed to compare the efficacy
and safety profiles of detemir and glargine as the basal insulin component of a basal–bolus regimen in people with type 2 diabetes.
Insulin aspart was used as the bolus insulin. The intention-to-treat population included 319 participants.
1.
2.
3.
Donnelly LA et al (2007) Q J Med 100: 345–50
Currie CJ et al (2012) Diabetes Care 35(6):1279-84.
Hollander P et al (2008) Clin Ther 30: 1976–87
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13
Is this for every patient?
 Too many injections
 Regimen complexity
 Patient
Frequent
BG
monitoring
– mental capacity
– scared of hypos
Insulin dose
adjustments
4-5
injections
a day
 Frequent BG measurements
 CHO awareness
 More injections -> more likely to skip
injections
 Body weight (not just young women)
 Tiring, long-tem commitment
 Not all patients want flexibility
1.
Donnelly LA et al (2007) Q J Med 100: 345–50
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Best regimen for the
right patient
Carb
awareness
Basal bolus a successful regimen
14
Summary
 There is some evidence that basal–bolus regimens provide glycaemic
benefit compared with twice-daily premixed insulin.
 However, there are some practical factors that make basal–bolus
regimens unfeasible for some people with type 2 diabetes.
Company Confidential © 2012 Eli Lilly and Company
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15
Summary
Options for people
with suboptimal control
on human premix
30/70
Move to an
analogue premix
with a similar ratio of
basal/prandial
coverage?
Company Confidential © 2012 Eli Lilly and Company
Company Confidential © 2012 Eli Lilly and Company
Consider using
basal plus bolus
insulin?
Move to a premixed
preparation with
greater prandial
coverage?
16
Moving to a premixed
insulin with a greater
prandial coverage
Rationale for considering “midmix” insulins
As people with diabetes get closer to HbA1c
targets, the need to manage PPG increases
Relative contribution (%)
100
Fasting plasma
glucose
Postprandial
glucose
70%
50
30%
0
>10.2
10.2–9.3 9.2–8.5
8.4–7.3
HbA1c (%) quintiles
<7.3
Adapted from Monnier L et al (2003) Diabetes Care 26: 881–5
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18
In people without diabetes, basal secretion
represents approximately 50% of total daily insulin
When the basal insulin secretion rate was
extrapolated over a 24-h period and
expressed as a percentage of the total 24h insulin secretion, basal secretion
represented 50.1±3.1% of the total 24-h
insulin secretion in normal subjects and
45.2±2.2% in obese patients.
Normal
Obese
Time (hours)
Polonsky KS et al (1988) J Clin Invest 81: 442–8
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19
% Total daily insulin dose
Patients with type 2 diabetes on intensive insulin
therapy regimens use 50% basal and 50% bolus
insulin
100
100
After titrating doses throughout the study each group
independently had a regimen that consisted of
approximately 50% basal and 50% preprandial insulin.
Multiple daily
injection (n=50)
Continuous
subcutaneous
insulin infusion
(n=48)
50
50
0
0
1
Basal dose
2
Bolus doses
Doses adjusted to achieve target preprandial and bedtime BG levels.
BG=blood glucose.
Herman WH et al (2005) Diabetes Care 28: 1568–73
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20
Currently available human and analogue
premixed insulins
Composition
Human insulins
Biphasic human insulin (Humulin® M3)
30% soluble insulin
70% isophane insulin
Biphasic human insulin (Insuman® Comb 15)
15% soluble insulin
85% isophane insulin
Biphasic human insulin (Insuman® Comb 25)
25% soluble insulin
75% isophane insulin
Biphasic human insulin (Insuman® Comb 50)
50% soluble insulin
50% isophane insulin
Biphasic insulin lispro (Humalog® Mix25)
25% lispro
75% lispro protamine
Biphasic insulin lispro (Humalog® Mix50)
50% lispro
50% lispro protamine
Biphasic insulin aspart (NovoMix® 30)
30% aspart
70% aspart protamine
Analogue insulins
Higher proportion of rapid-acting insulin component provides
greater activity in the postprandial period.
BG=blood glucose.
Herman WH et al (2005) Diabetes Care 28: 1568–73
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21
Moving to a premixed
insulin with a greater
prandial coverage
Evidence from clinical trials
Change in blood glucose from FBG (mmol/L)
Switching from twice-daily premixed insulin 30/70
or 25/75 to premixed insulin 50/50
Before switching to
biphasic insulin lispro 50/50*
12.5
After switching to
biphasic insulin lispro 50/50
10
n=13
Switching to twicedaily Mix 50/50 insulin
injections controlled
post-prandial blood
glucose levels and
stabilised diurnal
blood glucose
variations in patients
with type 2 diabetes
mellitus who had poor
glucose control on
insulin 30/70 or 25/75.
7.5
5
**
*
2.5
**
**
0
–2.5
FBG
AB
BL
AL
BS
AS
Bedtime
*Participants were receiving biphasic insulin aspart 30/70 (30% aspart, 70% aspart protamine), biphasic human insulin 30/70 (30% rapidacting insulin, 70% NPH), or biphasic insulin lispro 25/75 (25% lispro, 75% lispro protamine). **<0.05; ***P<0.01.
AB=after breakfast; AL=after lunch; AS=after supper; BL=before lunch; BS=before supper; FBG=fasting blood glucose; NPH=neutral
protamine Hagedorn.
Tanaka M, Ishii H (2010) J Int Med Res 38: 674–80
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23
Biphasic insulin lispro 50/50 (TID) vs premixed
human insulin 30/70 (BID)
Study design
 Primary measure: mean blood glucose (BG) change.
 Secondary measures: HbA1c, 7-point BG profile, and hypoglycaemia.
 6-month, single-centre, prospective, randomised, open-label,
2-period crossover.
 40 candidates (35 completed the study) on conventional insulin
therapy received biphasic insulin lispro 50/50 (TID) or human insulin
30/70 (30% regular/70% NPH, BID) for 12 weeks, and then switched
to the opposite sequence.
BID=twice-daily; NPH=neutral protamine Hagedorn; TID=three-times-daily.
Schernthaner G et al (2004) Horm Metab Res 36: 188–93
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24
Biphasic insulin lispro 50/50 (TID)
resulted in greater reduction in HbA1c compared
with premixed human insulin 30/70 (BID)
P<0.001
9
P=0.021
P=0.034
8
n=35
Mean HbA1c (%)
7
6
8.4
8.1
5
7.6
4
Both treatments
reduced HbA1c from
baseline, lispro 50/50
significantly more
than human 30/70.
3
2
1
0
Baseline
Human
30/70
Lispro
50/50
BID=twice-daily; TID=three-times-daily
Schernthaner G et al (2004) Horm Metab Res 36:188–93
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25
Biphasic insulin lispro 50/50 (TID) vs
premixed human insulin 30/70 (BID): summary
 Compared with human 30/70 (BID), lispro 50/50 (TID):
Produced a greater
decrease in mean blood
glucose.
Produced a greater
reduction in HbA1c.
Was associated with
smaller postprandial
blood glucose
excursions.
Improved overall
glycaemic control, and no
significant difference in
hypoglycaemia risk
between treatment
groups.
BID=twice-daily; TID=three-times-daily.
Schernthaner G et al (2004) Horm Metab Res 36:188–93
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26
Biphasic insulin lispro 50/50 (TID) vs
25/75 or 30/70 analogue mixture (BID)
 Primary measure:HbA1c
 Secondary measure: Change in HbA1c from baseline to
endpoint, percentage of patients who achieved a HbA1c <7%
and ≤6.5%, and SMBG
 This was a 16-week, multicenter, randomized, open-label, 2arm parallel study
 Patients continued with previous hypoglycemic treatment
during the lead-in period for 2 weeks (from visit 1 to 2),
Following the clinical assessments, eligible patients were
randomized (1:1) at visit 2 (week 0, baseline for the efficacy
measures) to 1 of the 2 insulin treatment strategies. One
strategy was based on LM50/50 3 times each day (TID group)
and the other on continuous progressive dose titration of twicedaily premixed insulin analogue (BID group).
Farcasiu E et al. (2011) Clin Ther ; 33:1682-93
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Results I
HbA1C*
TID Group (n=139)
BID Group (n=139)
Baseline
End Point
Baseline
End Point
P
8.71 (1.20)
7.7 (1.10)
8.67 (1.13)
7.84 (1.04)
0.2519ᵻ
HbA1C (%) mean
change (95% CI)
-1.0
(-1.17,-0.82)
-0.82
(-0.99,-0.66)
HbA1C of <7%
28.0 (21.4)
25.0 (18.5)
0.6455ᶊ
HbA1C of ≤6.5%
15.0 (11.5)
9.0 (6.7)
0.2024ᶊ
Weight Change,
(Kg)
1.3 (2.73)
0.4 (2.45)
0.0009ii
*Data
were mean (SD)
comparison at end point by ANCOVA
ᶊFisher exact test
ᵻTreatment
ii
Treatment comparison at end point by ANCOVA (repeated measures
Farcasiu E et al. (2011) Clin Ther ; 33:1682-93
Company Confidential © 2012 Eli Lilly and Company
)
Results II.
Hypoglycaemia (episodes/patient/30 days)
TID
BID
P value
overall
0.56 (0.10)
0.61 (0.10)
0.7230
nocturnal
0.04 (0.02)
0.13 (0.02)
0.0063
severe
0.00 (0.004)
0.01 (0.004)
0.8876
Farcasiu E et al. Clin Ther 2011; 33:1682-93
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29
Summary
When compared with a 30/70 premix BID, lispro
mix 50 TID therapy was associated with:
 Similar decrease in HbA1c
 Similar risk of overall hypoglycaemia
 Similar overall glycaemic control, while nocturnal hypoglycemia risk improved
between treatment groups
 Similar total daily insulin doses
 Greater weight gain
Farcasiu E et al. Clin Ther 2011; 33:1682-93
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30
Conclusion
 A number of factors will influence the decision regarding
choice of insulin regimen.
 A key priority is education for self-management to
optimise blood glucose control.
 There is a need to discuss and tailor the insulin regimen
to the individual.
 The patient’s journey will frequently involve change and
the role of the healthcare professional is to identify, action
and support it.
Company Confidential © 2012 Eli Lilly and Company
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31
Conclusion
 A three-times daily 50/50 analogue regimen
comprehensively addresses the postprandial glucose
peaks associated with the three main meals.
 There is evidence that biphasic insulin lispro 50/50 is
associated with glycaemic benefits compared with
biphasic human insulin 30/70, without a detrimental effect
on rates of hypoglycaemia.
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Company Confidential © 2012 Eli Lilly and Company
32
HUMALOG®MIX25™ VIAL, CARTRIDGE,ANDKWIKPEN™ HUMALOG® MIX50™ CARTRIDGE, AND KWIKPEN™
HUMULIN® VIAL,CARTRIDGE, AND KWIKPEN™
HUMULIN IS HUMANINSULIN(PRB)
Presentation Humulin Sis asterile solution of 100IU/ml humaninsulin available aseither 10ml vial or 3ml cartridge. Humulin I is a sterile suspension of 100IU/ml isophane
human insulin available aseither 10ml vial, 3ml cartridge, or 3ml KwikPen. Humulin M3 is a sterile suspension of 100IU/ml human insulin in the proportion of 30% soluble
insulin and 70% isophane insulin available aseither 10ml vial, 3ml cartridge, or 3ml KwikPen. UsesTreatment of patients with diabetes mellitus who require insulin for the
maintenance of glucose homeostasis. Dosage and Administration All Humulin preparations should be given by subcutaneous injection. Only Humulin Smay be given
intravenously. Resuspension Humulin Sdoes not require resuspension. Humulin I and Humulin M3 require resuspension immediately before use. Please see Summaries of
ProductCharacteristicsorPatientInformationLeafletsfordetailsonhowtodothis. Mixingof insulins (vialsonly):Humulin Smaybeadministeredin combinationwith Humulin I.
Theshorter- acting insulin (Humulin S)should bedrawn into thesyringefirst, to prevent contaminationof the vial bythelonger-acting preparation (Humulin I). It is advisable to
inject immediatelyafter mixing. WarningsandSpecialPrecautionsSomepatientstakinghumaninsulin mayrequireachange indosagefromthatusedwithanimal-source
insulins. If an adjustment is needed, it may occur with the first dose or during the first several weeks or months.Treatment with human insulin may cause formation of
antibodies,buttitresofantibodies are lower than those topurifiedanimal insulin.
Prices(Humulin)
£15.68- 1X10mlvialsHumulin S
£19.08- 5X3mlcartridgesHumulin S
£15.68- 1X10mlvialsHumulin I
£19.08- 5X3mlcartridgesHumulin I
£21.70- 5X3mlHumulin I KwikPens
£15.68- 1X10mlvialsHumulin M3
£19.08- 5X3mlcartridgesHumulin M3
£21.70- 5X3mlHumulin M3 KwikPens
Product Licence Numbers
HumulinS: HumulinI:
HumulinM3:
HumulinI KwikPen:
HUMALOGISINSULIN LISPRO(HUMANINSULIN ANALOGUE)
Presentation HumalogMix25is awhite, sterile suspensionof 100U/ml25%insulin lispro solution and75%insulin lispro protaminesuspensionavailableaseither10ml vial,
3ml cartridge,or3ml KwikPen.HumalogMix50is awhite, sterile suspensionof100U/ml50%insulin lispro solutionand 50%insulin lispro protaminesuspensionavailableas
either 3ml cartridge or3ml KwikPen.Uses Treatmentof patients with diabetes mellitus whorequire insulin for the maintenanceof normal glucosehomeostasis.Dosageand
Administration HumalogMix25orHumalogMix50maybe givenshortlybeforemeals and,whennecessary,canbegivensoonafter meals.HumalogMix25or HumalogMix50
should onlybegivenbysubcutaneous injection. Therapid onsetandearly peakof activity of Humalogitself is observedfollowing the subcutaneousadministration of Humalog
Mix25 or Humalog Mix50. The duration of action of the insulin lispro protamine suspension component is similar to that of a basal insulin. Warnings and Special
Precautions Usage in pregnancy: Data ona large number of exposed pregnancies do not indicate any adverse effect of insulin lispro on pregnancy or on the health of the
foetus/newborn.Administrationofinsulinlispro in childrenshould be considered only incase ofan expected benefitwhen compared tosoluble insulin.
Prices(Mix25/Mix50)
£16.61- 1 X10mlMix25 vial
£29.46- 5 X3mlMix25 cartridges
£30.98- 5 X3mlMix25 KwikPens
£29.46- 5 X3mlMix50 cartridges
£30.98- 5 X3mlMix50 KwikPens
Marketing Authorisation Numbers
HumalogMix25 vial: HumalogMix25
cartridge: HumalogMix50 cartridge: Humalog
Mix25 KwikPen:
EU/1/96/007/005
EU/1/96/007/008
EU/1/96/007/006
EU/1/96/007/033
Humalog Mix50 KwikPen:
EU/1/96/007/035
HUMALOG®(insulin lispro) is aregistered trademark of Eli Lilly andCompany. MIX25™, MIX50™, and KWIKPEN™are trademarks of Eli
Lilly and Company.
00006/0216 and0242
00006/0228 and0257
00006/0233 and0260
00006/0338
HumulinM3 KwikPen:
00006/0341
HUMULIN® (humaninsulin) is aregistered trademark of Eli Lilly andCompany. KWIKPEN™is a trademark of Eli Lilly and Company.
HUMALOG® VIAL,CARTRIDGE, ANDKWIKPEN™
HUMALOG IS INSULINLISPRO (HUMAN INSULINANALOGUE)
Presentation Humalogis availableasasolutionof100units/ml insulin lispro ineither10ml vial, 3ml cartridge,or3ml KwikPen(eachpencontains300unitsof insulin lisproin
3ml solution). It is alsoavailable asasolution of 200 units/ml in 3ml KwikPen(eachpencontains 600 units of insulin lispro in 3ml solution). Uses100 units/ml: Treatmentof
adults and children with diabetes mellitus who require insulin for the maintenance of normal glucose homeostasis. Humalog is also indicated for the initial stabilisation of
diabetes mellitus. 200 units/ml KwikPen: Treatment of adults with diabetes mellitus who require insulin for the maintenance of normal glucose homeostasis. Humalog 200
units/ml KwikPen is also indicated for the initial stabilisation of diabetes mellitus. Dosage and Administration Humalog may be given shortly before meals and, when
necessary,soonafter meals.It takeseffectrapidly(approximately15 minutes)andhasashorter durationofactivity (2to 5hours)ascomparedwith solubleinsulin.Humalog100
units/ml shouldbegivenbysubcutaneous injectionor bycontinuous subcutaneousinfusionpump.If necessary,Humalogmayalsobe administeredintravenously,forexample,
for thecontrolofbloodglucoselevelsduringketoacidosis, acuteillness, orperioperatively.Humalog200units/ml KwikPenshould begivensubcutaneously. It should notbeused
in an insulin infusion pump, or given intravenously. Humalog 100 units/ml KwikPenand Humalog 200 units/ml KwikPen Humalog KwikPen is available in two strengths. For
both, theneededdoseisdialledinunits.Bothpre-filled pens,theHumalog100units/ml KwikPen andtheHumalog200units/ml KwikPen,deliver1-60 units instepsof1unit in
asingle injection. Thedose counter shows the number of units regardless of strength and nodose conversion should bedonewhentransferring apatient to anew strength.
Humalog200 units/ml KwikPen shouldbereserved for the treatment of patients with diabetes requiring daily dosesof more than 20 units of rapid-acting insulin. Theinsulin
lispro solution containing200 units/ml should notbe withdrawnfrom the pre-filled pen.Warnings and Special PrecautionsUsagein pregnancy: Data onalargenumberof
exposedpregnanciesdonotindicateanyadverseeffectof insulin lispro on pregnancyoronthehealthof thefoetus/newborn.Insulin lispro shouldbeusedinchildrenonly when
anadvantage is expectedcomparedto soluble insulin, for example, in the timing of the injection in relation to meals. Avoidanceof medication errors whenusing insulin lispro
(200 units/ ml) in pre-filled pen: Theinsulin lispro solutionfor injection containing200 units/ml must notbe transferredfrom thepre-filled pen,theKwikPen,toasyringe. The
markingsonthe insulin syringe will not measurethedosecorrectly.Overdosecanresult causing severehypoglycaemia.Theinsulin lispro solutionfor injection containing200
units/ml mustnotbetransferredfromtheKwikPento anyotherinsulin deliverydevice,including insulin infusionpumps.Patientsmustbeinstructedto alwayschecktheinsulin
labelbeforeeachinjectiontoavoidaccidentalmix-ups betweenthetwo differentstrengthsofHumalog as wellas otherinsulin products.
Prices(Humalog)
£16.61- 1X10ml vials
£28.31- 5X3ml cartridges
£29.46- 5X3mlHumalog 100units/ml KwikPens
£58.92- 5X3mlHumalog 200units/ml KwikPens
Marketing Authorisation Numbers
LILLY INSULINS GENERALINFORMATION
SeeSummariesofProductCharacteristics for additionalinformation,includingtime-action profiles ofall formulations.
Dosage and Administration (general) Thedosage or type of insulin should be determined according to the requirements of the patient. Thetime course of action of any
insulin mayvary considerablyin differentindividualsoratdifferent timesin thesameindividual.Vialsarepacked with instructions regardingdosepreparationandadministration,
andthese should becarefully followed. Lilly insulin cartridges aretobeusedwithaCEmarkedpenaccordingto theinstructions providedbythedevicemanufacturer. Patients
should beadvisedtoalwayskeepasparesyringe andvial, orasparepenandcartridge.Prefilledpensarepackedwith instructionsonhowtouse them.Thesedirectionsshould
befollowed carefully. Donotuseif, after resuspension,the insulin remainsat thebottom, if thereare clumpsin the insulin, or if solid whiteparticles stick to thebottom or wall
giving the container afrosted appearance. Contra-indications Hypersensitivity to the active ingredient or to anyof the excipients. Hypoglycaemia. Warnings and Special
Precautions (general) Transferringapatient to another type or brand of insulin shouldbedoneunder strict medical supervision. Changes in strength, brand, type, species,
and/or methodof manufacturemay result in theneedforachangeindosage.Forfastacting insulins, anypatientalsoonbasal insulin mustoptimisedosageof bothinsulinsto
obtain glucose control across the whole day, particularly nocturnal/fasting glucose control. Changes in early warning symptoms of hypoglycaemia may occur on transfer
betweendifferent typesof insulinproducts. Insulin requirements maybe reducedin thepresenceof renalimpairmentorhepaticimpairment. However,inpatients with chronic
hepatic impairment, an increase in insulin resistance may lead to increased insulin requirements. Insulin requirements may be increased during illness or emotional
disturbances. Casesof cardiac failure havebeenreported whenpioglitazone wasused in combination with insulin. If the combination is used,patients should beobservedfor
signs and symptoms of heart failure and pioglitazone discontinued if any deterioration occurs.Pregnancy and Lactation Insulin requirements usually fall during the first
trimester and increaseduringthesecondandthird trimesters. Patientsshouldbeadvisedto inform their doctorsif theyarepregnantorcontemplating pregnancy.Driving,etc
The patient’s ability to concentrate and react may be impaired as a result of hypoglycaemia. This may constitute a risk in situations where these abilities are of special
importance (eg,drivingacaroroperatingmachinery). UndesirableEffectsHypoglycaemia is the mostfrequentundesirableeffectof insulin therapy.Localallergy iscommon
andusually resolves. Systemicallergy is rarebutpotentially moreserioussinceseverecasesmaybelife-threatening. Lipodystrophyis uncommon.Forfull details of theseand
other side-effects, pleaseseethe Summaryof Product Characteristics, which is available at http://www.medicines.org.uk/emc/. LegalCategoryPOMDateofPreparation
or Last ReviewJanuary 2015 FullPrescribing Information is Available FromEli Lilly andCompanyLimited, Lilly House,Priestley Road Basingstoke, Hampshire,RG24
9NLTelephone:Basingstoke(01256)315000E-mail:ukmedinfo@ lilly.comWebsite:www.lillypro.co.uk
UKHMG00716(1) October 2015
Humalogvial: Humalogcartridge:
Humalog 100 units/ml KwikPen:
Humalog 200 units/ml KwikPen:
®
EU/1/96/007/002
EU/1/96/007/004
EU/1/96/007/031
EU/1/96/007/041
HUMALOG Confidential
(insulin lispro) is aregistered
trademark
of Eli Lilly
andCompany
Company. KWIKPEN™is a trademark of Eli Lilly and Company.
Company
© 2012
Eli Lilly
and
Adverse events should be reported. Reporting forms and further information can be found at:
www.mhra.gov.uk/yellowcard.
Adverse events and product complaints should also
be reported to Lilly: please call Lilly UK on 01256 315 000.