An Introduction To Insulin Therapy
An Introduction To Insulin Therapy
An Introduction To Insulin Therapy
premixed
T1DM
T2DM
titration
An Introduction to
Insulin Therapy in
st
the 21 Century
glycemic control
A1C levels
Education Partner
Basal-bolus
hypog
Calculate appropriate insulin doses for initiating basal and basal-prandial insulin regimens in T2DM.
Demonstrate best practices in insulin injection and self-monitoring of blood glucose (SMBG) techniques to improve
treatment adherence and potentially impact patient outcomes.
Apply pattern recognition to SMBG data to appropriately titrate insulin doses and adjust insulin regimens to specific patient
needs.
Summarize the efficacy and safety findings from clinical trials of investigational insulins and the combination of incretinbased therapies with insulin.
Faculty
Debbie Hinnen, ARNP, BC-ADM, FAAN
Director of Education Services
Mid-America Diabetes Associates
Wichita, Kansas
Ms Hinnen has been a diabetes educator for over 30 years. A clinical nurse specialist and director of education services, she
currently works with a multidisciplinary team at Mid-America Diabetes Associates, which provides diabetes care and education.
The cornerstone of their program is a 3-day comprehensive self-management course that serves nearly 1000 people with diabetes
per year.
Ms Hinnen is involved extensively with the American Association of Diabetes Educators (AADE) and previously served as their
national president and chair of the foundation. She was awarded the AADEs prestigious Distinguished Service Award in the
summer of 2001. Ms Hinnen has also served on the national board of directors of the American Diabetes Association and as one
of the editors for the journal Diabetes Spectrum. Ms Hinnen holds faculty positions with the pharmacy department at the University
of Kansas, and with the graduate nursing department and the physician assistant program, both at Wichita State University. She
was inducted as a fellow into both the American Academy of Nursing in 2003 and the AADE in 2010.
Etie Moghissi, MD, FACP, FACE
Clinical Associate Professor
University of California, Los Angeles
Los Angeles, California
Dr Moghissi is a clinical associate professor of medicine at the University of California, Los Angeles, and has a private practice in
Marina del Rey, California. As a native of Shiraz, Iran, she earned her medical degree from Pahlavi University School of Medicine
in Shiraz. She completed an internal medicine residency at St. Lukes-Roosevelt Hospital at Columbia University in New York
City and a fellowship in endocrinology at the University of Southern California in Los Angeles. She is board certified by the
American Board of Internal Medicine and the American Board of Endocrinology.
Dr Moghissi coauthored the 2011 American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Developing a
Diabetes Mellitus Comprehensive Care Plan and currently serves as the chair of the American Association of Clinical Endocrinologists
(AACEs) Diabetes Resource Center Task Force. She chaired and was the lead author of the 2009 AACE/American Diabetes
Association (ADA) Consensus Statement on Inpatient Glycemic Control. Dr Moghissi was also cochair of the AACE Inpatient Diabetes
Consensus Conference and Position Statement (2004) and the AACE/ADA Inpatient Diabetes Call to Action Consensus Conference and
Position Statement (2006). In 2007, she led the effort to create the AACE Inpatient Glycemic Control Resource Center on AACEs
website. Her efforts have been instrumental in driving a major shift in optimizing the care of hospitalized patients with diabetes.
Session 3
Dr Moghissi is the president-elect of the AACE and past president of its California chapter. Her areas of interest include direct
patient care and teaching in the field of diabetes, and she has lectured extensively on these topics on both the national and
international levels.
Javier Morales, MD
Vice President
Principal Trials Investigator
Advanced Internal Medicine Group, PC
New Hyde Park, New York
Dr Morales is in private practice with the Advanced Internal Medicine Group in New Hyde Park, New York. After graduating
from the University of Medicine and Dentistry of New Jersey, he completed residencies at Memorial Sloan-Kettering Cancer
Center and North Shore University Hospital, where he served as chief medical resident. Dr Morales serves on multiple
committees at St. Francis Hospital in Roslyn, New York. In addition to authoring several publications, he has served as principal
investigator for several different studies and clinical trials. He is active in the educational sector and has been a presenter at many
Pri-Med symposia. He also serves as a clinical instructor for several nurse practitioner, physician assistant, and internal medicine
residency programs at North Shore University Hospital and Winthrop University Hospital. Dr Morales is an avid musician and
percussionist, and he is fluent in Spanish, Italian, and Portuguese.
The content collaborators at the Institute for Medical and Nursing Education, Inc., report the following:
Amy Carbonara, Director of Program Development, has no financial relationships to disclose.
Robin Devine, DO, Medical Writer, has no financial relationships to disclose.
Angela McIntosh, PhD, Scientific Director, has no financial relationships to disclose.
Marge Tamas, Editorial Manager, has no financial relationships to disclose.
Steve Weinman, RN, Executive Director, has no financial relationships to disclose.
Acronym List
Acronym
A1C
AACE
AADE
ACE
ADA
AE
ASP
B
BBT
BG
Bi-ASP
BID
BMI
CGM
CKD
Definition
glycosylated hemoglobin A1C
American Association of Clinical
Endocrinologists
American Association of Diabetes
Educators
American College of Endocrinology
American Diabetes Association
adverse event
insulin aspart
breakfast
basal bolus therapy
blood glucose
biphasic aspart
twice daily
body mass index
continuous glucose monitoring
chronic kidney disease
Acronym
CSII
CVD
D
DEG
DET
DPP-4
EPM
EXN
FBG
FPG
FPG LL
FPG UL
GLAR
GLP-1
GLU
HS
IFG
Definition
continuous subcutaneous insulin
infusion
cardiovascular disease
dinner
insulin degludec
insulin detemir
dipeptidyl peptidase-4
events/patient-month
exenatide
fasting blood glucose
fasting plasma glucose
fasting plasma glucose lower limit
fasting plasma glucose upper limit
insulin glargine
glucagon-like peptide-1
insulin glulisine
at bedtime
impaired fasting glucose
Session 3
Acronym
IGT
ILPS
ITT
L
LIRA
LIS
LM 50/50
LM 75/25
LY
MDI
MET
NA
NDA
NPH
NPL
OADs
OD
PBO
PCP
Definition
impaired glucose tolerance
insulin lispro protamine suspension
intention-to-treat
lunch
liraglutide
insulin lispro
insulin lispro protamine (50%)/insulin
lispro (50%)
insulin lispro protamine (75%)/insulin
lispro (25%)
pegylated insulin lispro
multiple daily injections
metformin
not applicable
New Drug Application
neutral protamine Hagedorn
insulin lispro protamine suspension
oral antidiabetes agents
once daily
placebo
primary care physician
Acronym
PD
PH20
PIO
PK
PPG
PPG UL
QHS
QOL
R
RA
RHI
SAXA
SC
SITA
SMBG
STeP
SU
T1DM
T2DM
TDD
TZD
U
Definition
pharmacodynamics
recombinant human hyaluronidase
pioglitazone
pharmacokinetics
postprandial glucose
postprandial upper limit
every night at bedtime
quality of life
recombinant
receptor agonist
regular human insulin SAXA
saxagliptin
subcutaneous
sitagliptin
self-monitoring blood glucose
Structured Testing Program
sulfonylurea
type 1 diabetes
type 2 diabetes
total daily dose
thiazolidinedione
unit
American Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed. Alexandria, VA: American Diabetes
Association, Inc; 2011:1-68.
Freeman JS. Insulin analog therapy: improving the match with physiologic insulin secretion. J Am Osteopath Assoc. 2009;109(1):2636.
Frid A, Hirsch L, Gaspar R, et al. New injection recommendations for patients with diabetes. Diabetes Metab. 2010;36(suppl 2):S3S18.
Handelsman Y, Mechanick JI, Blonde L, et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical
Practice for developing a diabetes mellitus comprehensive care plan. Endocr Pract. 2011;17(suppl 2):1-53.
Hinnen D, Tomky D. In: Mensing C, et al, eds. The Art and Science of Diabetes Self-Management: A Desk Reference for Healthcare
Professionals. Chicago, IL: American Association of Diabetes Educators; 2011:531-576.
Hirsch E, Bergenstal RM, Parkin CG, et al. A real-world approach to insulin therapy in primary care practice. Clin Diabetes.
2005;23(2):78-86.
Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for
the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European
Association for the Study of Diabetes. Diabetes Care. 2009;32(1):193-203.
Parkin CG, Davidson JA. Value of self-monitoring blood glucose pattern analysis in improving diabetes outcomes. J Diabetes Sci
Technol. 2009;3(3):500-508.
Rodbard HW, Jellinger PS, Davidson JA, et al. Statement by an American Association of Clinical Endocrinologists/American
College of Endocrinology consensus panel on type 2 diabetes mellitus: an algorithm for glycemic control. Endocr Pract.
2009;15(6):541-559.
Skyler JS. In: Lebovitz HE, ed. Therapy for Diabetes Mellitus and Related Disorders. Alexandria, VA: American Diabetes Association,
Inc; 2004:207-223.
Session 3
Drug List
Generic
albiglutide
alogliptin
bromocriptine
colesevelam
dulaglutide
exenatide BID
exenatide QW
glimepiride
glipizide
glyburide
insulin detemir
insulin glargine
linagliptin
liraglutide
lixisenatide
Trade
Syncria; investigational; not FDA approved
Nesina; approved only outside the United States
Cycloset
Welchol
investigational; not FDA approved
Byetta
Bydureon; submitted for FDA approval
Amaryl
Glucotrol
DiaBeta, Glynase, Micronase
Levemir
Lantus
Tradjenta
Victoza
Lyxumia; submitted for approval by the European
Medicines Agency
Fortamet, Glucophage, Glumetza, Riomet
Actos
Avandia
Onglyza
Januvia
Galvus; approved only outside the United States
metformin
pioglitazone
rosiglitazone
saxagliptin
sitagliptin
vildagliptin
Insulin 101:
Basal Insulin Therapy
DebbieHinnen,ARNP,BCADM,CDE,FAAN,FAADE
DirectorofEducationServices
MidAmericaDiabetesAssociates
Wichita,Kansas
Basicsofinsulintherapy
Currentlyavailablebasalinsulins
Initiatingbasalinsulintherapy
Optimizinginsulininjectiontechniques
Glucose (mg/dL)
Part1:Basalinsulintherapy
350
300
250
200
150
100
50
Relative Amount
250
Prediabetes
(Obesity, IFG, IGT)
Postmeal Glucose
Diabetes
diagnosis
Fasting glucose
Insulin resistance
-cell failure
200
150
100
Insulin level
50
0
15
10
0
Onset
diabetes
10
15
20
25
30
Years
Macrovascular changes
Clinical
features
Microvascular changes
KendallDM,etal.AmJMed.2009;122:S37S50;
KendallDM,etal.AmJManag Care.2001;7(10suppl):S327S343.
120
BasalPlus
Time
60
40
Time
24h
1000
1400
1800
2200
0200
InsulinEffect
Time
0600
24h
BasalBolus
Premixed/Biphasic
20
0600
InsulinEffect
InsulinEffect
80
InsulinEffect
MeanInsulinLevel(U/mL)
Basal
Control
Diabetic
100
24h
24h
TimeofDay
Bars denote standard error of the mean.
=insulininjection
24weeknoninferioritytrialof973insulinnaive
T2DMpatientsinadequatelycontrolledonOADs
A1C>7.5%despitetheuseof2or3OADs
A1C>9.0%despitepreviousT2DMpharmacologictherapy
InsulinglargineQD
A1C>9.0%plussymptomsinanewlydiagnosedT2DM
Insulindetemir BID
inA1C,frombaseline,%
Earlyinitiationisassociatedwithimprovedcellfunction
andreducedinsulinresistance
CombinationwithotheragentsincludingOADs,prandial
insulin,andincretinbasedtherapiescanimproveglycemic
control
Similarhypoglycemiarates
(<30%symptomatic)
Weightgainwashigherwith
insulinglargine (+0.77kg;
P <.001)
0
0.5
1
1.5
1.46
Finalinsulindoses(U/day):
Insulinglargine:43.5
Insulindetemir:76.5(P <.001)
1.54
P =.149
Part1:Basalinsulintherapy
NPHInsulin
InsulinGlargine
InsulinDetemir
Human;
intermediateacting
Analogue;
longacting
Analogue;
longacting
24 hours
N/A
N/A
Peak
410hours
Nopronounced
peak
Relatively flat
Effective
Duration
1016hours
Upto24hours
Upto24hours
Basicsofinsulintherapy
Currentlyavailablebasalinsulins
InsulinType
Initiatingbasalinsulintherapy
Onset
Optimizinginsulininjectiontechniques
LongactinginsulinanaloguesarepreferredoverNPHinsulin
becausethey:
Part1:Basalinsulintherapy
Basicsofinsulintherapy
GIRtoMaintainConstant
BGLevel(mg/kg/min)
Donotexhibitapronouncedpeakinactivity
Havemorepredictabletimeactionprofilesandlesswithin/between
patientvariability
Areassociatedlessnocturnalhypoglycemia
Detemir
NPH
7
6
5
4
3
2
1
0
Subject214
12
16
20
24
7
6
5
4
3
2
1
0
4
12
16
Initiatingbasalinsulintherapy
Optimizinginsulininjectiontechniques
Glargine
Subject215
Currentlyavailablebasalinsulins
20
24
7
6
5
4
3
2
1
0
Subject231
12
16
20
24
ElapsedTime(hours)
N = 54 T1DM patients.
Euglycemic glucose clamp study, 4 trials/subject.
ADA/AACE/AADE
Initiateat10U/day
Safetyandefficacyhavebeendemonstratedin3trials
AT.LANTUS (glargine)
or
Useweightbasedapproach:0.10.2U/kg/day
PREDICTIVE303(detemir)
MonitorFPG todeterminedosageadjustments
INITIATEPlus(biphasicaspart 70/30)
Anticipatedbenefits
Costsavings
AADE
ADA
TitratetoFPG 70130mg/dL
FPG<70:reducedoseby
4U or10%TDD
FPG>130:increasedose
by24U every3days
Fewerofficevisits
Equivalentorfewerhypoglycemicepisodes
Increasedoseby2U every3days
untilFPGis70to110mg/dL
or
Increaseby1U/dayuntilFPG<
100mg/dL
Greaterpatientsatisfaction(increasedautonomy)
Confirmingbenefits
Patientcenteredoutcomesstudyisinprogress(Di@log)
A1C
AACE
ADA
6.5%
<7.0%
BloodGlucose(mg/dL)
300
SMBGReadingsa
FastingPlasmaGlucose
70110 mg/dL
70130mg/dL
Preprandial
N/A
Postprandial
70140mg/dLb
<180mg/dLc
N/A
100140mg/dL
Bedtime
b
c
More than half of the readings should fall within this range.
2-hour PPG reading.
1 to 2-hour PPG reading.
200
FPGUL
100
FPGLL
50
mg/dL
PPGUL
150
Bothorganizationsrecognizethatmoreorlessstringentgoalsmaybe
appropriateforsomeindividuals
a
250
Before
breakfast
2hafter
breakfast
Before
lunch
2hafter
lunch
Before
dinner
2hafter
dinner
Before
bed
83
111
79
114
82
118
87
American Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed. 2011:1-68.
Accu-Chek Connect: Quick Reference Guide:
http://behavioraldiabetesinstitute.org/studies/downloads/ACCU-CHEK_Quick_Reference_Guide.pdf.
250
250
BloodGlucose(mg/dL)
BloodGlucose(mg/dL)
200
PPGUL
150
FPGUL
100
FPGLL
50
0
mg/dL
Before
breakfast
2hafter
breakfast
Before
lunch
2hafter
lunch
Before
dinner
2hafter
dinner
Before
bed
173
204
168
199
174
206
183
200
FPGUL
100
FPGLL
50
0
mg/dL
American Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed. 2011:1-68.
Accu-Chek Connect: Quick Reference Guide:
http://behavioraldiabetesinstitute.org/studies/downloads/ACCU-CHEK_Quick_Reference_Guide.pdf.
PPGUL
150
Before
breakfast
2hafter
breakfast
Before
lunch
2hafter
lunch
Before
dinner
2hafter
dinner
Before
bed
52
90
48
90
55
90
65
American Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed. 2011:1-68.
Accu-Chek Connect: Quick Reference Guide:
http://behavioraldiabetesinstitute.org/studies/downloads/ACCU-CHEK_Quick_Reference_Guide.pdf.
BloodGlucose(mg/dL)
300
Part1:Basalinsulintherapy
250
Basicsofinsulintherapy
Currentlyavailablebasalinsulins
200
150
100
PPGUL
Initiatingbasalinsulintherapy
FPGUL
Optimizinginsulininjectiontechniques
FPGLL
50
0
3:00AM
mg/dL
45
Before 2hafter
breakfast breakfast
213
144
Before
lunch
127
2hafter
lunch
123
Before
dinner
75
2hafter
dinner
110
Before
bed
74
American Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed. 2011:1-68.
Accu-Chek Connect: Quick Reference Guide:
http://behavioraldiabetesinstitute.org/studies/downloads/ACCU-CHEK_Quick_Reference_Guide.pdf.
aMay
Pen
Syringe
1. Prime pentocheckforflow(adropof
insulinshouldbevisibleatthetipof
theneedle)
2. Ensuredosingdialissetto0anddial
indoseofinsulintobedelivered
3. InsertneedlequicklyintotheSCtissue
4. Fullydepressthumbbutton
5. Countslowlyto10before
withdrawingtheneedlea
6. Followinginjection,removeneedle
anddiscardproperly
7. Neverleaveneedlesattachedtothe
pen
1. Drawupequivalent amountofairinto
syringeandinjectintovialpriorto
drawingupinsulin
2. Tapbarrelandpushplungerto
removeairbubbles
3. InsertneedlequicklyintotheSCtissue
4. Depressplungerfully
5. Followinginjection,removeneedle
anddiscardproperly
6. Neverusesyringeneedlesmorethan
once
UpperArm
Thigh
Abdomen
Buttocks
Ensureinjectionintosubcutaneoustissue,notintramuscularly
Penetrateskinquickly,butinjectslowly
Allownewlyopenedinsulintocometoroomtemperature
Ifusingalcohol,allowtodrybeforeinjectinginsulin
Heat/coldisnotrecommendedasitcanalterabsorption
Resultsfromthegrowtheffectsofinsulinandinductionoflocalgrowth
factorsduetorepeatedinjection
Useshorterlengthneedles(4,5,or6mm)
Oftenlesspainfultoinjectintoareasoflipohypertrophy BUT
Iflongerneedles(8mm)arebeingused,skinpinchtechnique
shouldbeemployed
absorptionofinsulinisalteredandcanleadtohypo orhyperglycemia
Itisrecommendedthatpatientsdonottoinjectintothesesites
Useanewneedlewitheveryinjection
Prevention:
Repeatedusebluntsneedles
Newneedlesarecoatedwithsiliconelubrication
Rotatesites avoidrepeatedinjectionintothesamearea
Useanewneedlewitheveryinjection
King L, et al. Nurs Stand. 2003;17:45-52;
Wallymahmed ME, et al. Postgrad Med. 2004;80:732-733.
5mmx31G
4mmx32G
3/16
5/32
8mmx31G
12.7mmx29G
5/16
1/2
Usetheshortestneedlepossiblewheninitiatinginsulintherapy
Thereisnomedicalreasontouseaneedlelongerthan8mm
Becton Dickinson Diabetes. Step by step injection guide. 2012; www.bd.com/us/diabetes.
Becton Dickinson Diabetes. BD pen needles fit these pens.
http://www.bd.com/us/diabetes/hcp/main.aspx?cat=3067&id=3156
Frid A, et al. Diabetes Metab. 2010;36(suppl 1):S3-18.
Insulinprescriptionshouldinclude:
BasalinsulincanbeinitiatedthroughouttheT2DMspectrum
Typeofinsulin
Insulininjectionissimpleandstraightforward
Numberofunits,vials/pens
Frequencyofdosing
Alwaysinjectintosubcutaneoustissue,notmuscle
Besuretorotateinjectionsites
Diagnosiscode
Supplies
Analoguebasalinsulins areoftenpreferredoverhuman
insulins (NPH/regular)becauseoftheirmorephysiologic
profiles
Penneedlesorsyringe/needles
SMBG supplies(lancets,teststrips,
controlsolution,log)
Basalinsulinisgenerallyinitiatedat10U/dayor0.10.2
U/kg/dayandtitratedtoachieveFPG glucosetargets
Insulintitrationinstructions
Needledisposal patientresources
Hypoglycemiatreatmentprotocol
Properinjectiontechniqueshouldbereinforcedperiodically
andinjectionsitesshouldbeexaminedregularly
Glucagonkit(ifpatientisatsignificantriskforhypoglycemia)
Diabeteseducationreferral
Joslin Diabetes Center. Writing Prescriptions for Diabetes Medications and Devices.
http://www.bd.com/us/diabetes/hcp/main.aspx?cat=3065&id=63268. Accessed January 18, 2012.
INSULIN 101:
BASAL-PRANDIAL
INSULIN THERAPY
Part2:Basalprandialinsulintherapy
Indicationsforbasalprandialinsulintherapy
Currentlyavailableprandialinsulins
Initiatingbasalprandialinsulintherapy
JavierMorales,MD
InsulintitrationusingSMBG data
St.FrancisHospital
AdvancedInternalMedicineGroup
NewHydePark,NewYork
Theindividualisnotmeetingglycemictargetsonbasal
insulin
Postprandialhyperglycemia
ContributiontoDiurnal
Hyperglycemia(%)
100
ElevatedA1CdespitenormalFPG (intheabsenceof
availablePPGreadings)withbasalinsulin
FPG withbasalinsuliniswithintargetedrange,butPPGis
persistentlyabovegoal
Furtherincreasesinbasalinsulinresultinhypoglycemia
Fastinghyperglycemia
80
a,b
60
40
a
a
20
0
<7.3%
Somepatientsmayonlyrequireprandialinsulinwith
theirlargestmeal
7.3%to
8.4%
8.5%to
9.2%
9.3%to
10.2%
>10.2%
A1CQuintile
Therelativecontributionofpostprandialhyperglycemiatooverallhyperglycemia
isgreateratA1Clevelsnear7%.
American Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed.
2011:1-68; Skyler JS. In: Lebovitz HE, ed. Therapy for Diabetes Mellitus and Related Disorders.
Alexandria, VA: American Diabetes Association, Inc.; 2004:207-223; Holman RR, et al. N Engl J Med.
2007;357(17):1716-1730; Davidson MB, et al. Endocr Pract. 2011;17(3):395-403.
a
b
Regular
Insulin
Insulin
Lispro
Insulin
Aspart
Insulin
Glulisine
Human;
shortacting
Analogue;
rapidacting
Analogue;
rapidacting
Analogue;
rapidacting
Indicationsforbasalprandialinsulintherapy
Currentlyavailableprandialinsulins
Insulintype
Initiatingbasalprandialinsulintherapy
InsulintitrationusingSMBG data
Onset, h
0.51
<0.30.5
<0.25
<0.25
Peak, h
23
0.52.5
0.51.0
11.5
Effective duration,h
36
36.5
35
35
30to45
15to
immediately
after
5to10
15 to+20
Injection:
mealtiming, m
BasalBolusInsulin
Currentlyavailableprandialinsulins
Initiatingbasalprandialinsulintherapy
InsulintitrationusingSMBG data
Premixed/BiphasicInsulin
Insulininjection
InsulinEffect
InsulinEffect
Indicationsforbasalprandialinsulintherapy
Insulininjection
24h
Time
24h
Time
Prandialinsulincanbegivenwith1,2,orall3mealsoftheday
Hirsch IB, et al. Clin Diabetes. 2005;23(2):78-86; Skyler JS. In: Lebovitz HE, ed. Therapy for Diabetes Mellitus
and Related Disorders. Alexandria, VA: American Diabetes Association, Inc.; 2004:207-223; American
Diabetes Association. Practical Insulin: A Handbook for Prescribing Providers. 3rd ed. 2011:1-68.
Assumespatientisalreadyusingbasalinsulin
TotalDailyDose(TDD)Insulina =
Basal(50%)+Prandial(50%;dividedamongmeals)
Method1:weightbased
Totaldailydose(TDD)0.51.0U/kg/day
Basaldoseis50%ofTDD
Basal
10U
Dividetheremaining50%across3meals
Assumesconsistentcarbohydratecontentwitheachmeal
30U
Breakfast (100gCHO)
10U
Lunch (100gCHO)
10U
Method2:insulin:carbohydrateratiobased
Dinner (100gCHO)
Initiallyestimateprandialdosesat1.01.5U/10g
carbohydrate
a
Skyler JS. In: Lebovitz HE, ed. Therapy for Diabetes Mellitus and Related Disorders. 2004:207-223;
Hinnen D, Tomky D. In: Mensing C, et al, eds. The Art and Science of Diabetes Self-Management: A
Desk Reference for Healthcare Professionals. 2011:531-576.
TotalDailyDose(TDD)Insulina =
Basal(50%)+Prandial(50%;dividedamongmeals)
Premeal
5U
Basal
288
252
14
216
180
144
15U
108
Lunch (100gCHO)
Dinner (150gCHO)
72
36
Fasting
Postmeal
16
10
Breakfast (50gCHO)
30U
18
12
10U
Postbreakfast Prelunch
Postlunch
Predinner
Postdinner
Bedtime
Regularhumaninsulin
needstobeinjected3045
minutesbefore meals
Lessconvenientfor
patient
Rapidactinginsulin
analogues(aspart,glulisine,
lispro)canbeinjected015
minutesbefore meals
Insulinlispro andinsulin
glulisine canbesafely
injectedimmediatelyaftera
meal
Ratner R, et al. Diabetes Obes Metab. 2011; 13: 1142-1148; Luijf YM, et al.
Diabetes Care. 2010;33(10):2152-2155; Cobry E, et al. Diabetes Technol Ther.
2010;12(3):173-177; Rassam AG, et al. Diabetes Care. 1999;22(1):133-136;
American Diabetes Association. Practical Insulin: A Handbook for Prescribing
Providers. 3rd ed. 2011:1-68.
SMBG enablesappropriatemanagementofglycemia
Indicationsforbasalprandialinsulintherapy
Detecting/avoidinghyperglycemia
Currentlyavailableprandialinsulins
Detecting/avoidinghypoglycemia
Initiatingbasalprandialinsulintherapy
SMBG frequencyandschedulecanbevariedtomeet
individualneeds
InsulintitrationusingSMBG data
ClinicianreviewofSMBG logsisessential
Helpsassessefficacyandsafetyofantidiabetic regimen
Facilitatesproviderpatientpartnership
Parameter/
Characteristic
Largenumericaldisplay
Backlitdisplayorglowinthe
SimpleSTEP
Basalinsulin titration
darkdisplay
Prandialdoseaddition
Graphingcapability
Size
Compact,medium,orlarge
ExtraSTEP
Basedonaverageof3prebreakfastPGmeasurements
Prandial insulintitration
Every12wks,ifneeded
Tolargestperceived
meal
Basedonpremeal PG
Basedonpostmeal PG
Largememorycapacity
SMBG
AudioreportingofSMBG
results
Participantadjustments?
Computerupload
PG,plasmaglucose;SMBG, selfmonitoringofbloodglucose.
3X4point profiles
Beforeeachmeal
Bedtime
Every12wks,ifneeded
Tomealwithhighest
postmeal PGincrease
3X 6pointprofiles
Beforeeachmeal
2haftereachmeal
Yes
Yes
ExtraSTEP (n=146)
Hypoglycemia(BG<56mg/dL)
Efficacy
15
BLA1C:8.7%8.9%
A1C(%)
0.5
1.0
1.1
1.5
1.3
2.0
2.5
Wt: 2.7 kg
HypoEventRate(EPY)
0.5
0.0
10
ClinicianNeeds
Appropriateglycemic
targets(fasting,
postprandial)
MustreviewSMBG logs
Whentotest
5.98 5.87
Whattheresultsmean
1.39 1.01
2.0 kg
PatientEducationNeeds
Minor
Nocturnal
Whentotakeaction
0.04 0.01
Musttakeactionbasedon
SMBG data
Lackofclinician
review/actionmayrender
SMBG ineffective
Major
3.0
Final insulin doses (U/kg/d): SimpleSTEP, 1.25 0.59; ExtraSTEP, 1.37 0.70.
Hypoglycemia definitions: minor, self-treated; major, assistance required.
Action
Allreadingsabovetargets
Increasebasaldose
PPGreadingsabovetargets
Add/increaseprandialdose
Hypoglycemia
Decreaseinsulindose
Frequent,unpredictableglycemic
fluctuations
Maybeapumpcandidate
physiologicprofilescomparedwithhumanprandialinsulin
Ifglucoselevelsareoutoftargetat: Adjustthisinsulincomponent:
Postbreakfast/prelunch
Prebreakfast prandial
Postlunch/predinner
Prelunch prandialand/ormorningbasalinsulin
Midafternoon
Morningbasalinsulin
Postdinner/bedtime
Predinner prandial
Earlymorning
Eveningbasalinsulin
Prandialinsulinisinitiatedas50%oftheTDDofinsulinand
dividedamongmealsorwithaninsulin:carbohydrateratio
SMBGplaysanimportantroleindeterminingtheefficacy
andsafetyofapatientsantidiabeticregimen
Hinnen D, Tomky D. In: Mensing C, et al, eds. The Art and Science of Diabetes Self-Management Desk
Reference. 2011;20:531-576.
http://behavioraldiabetesinstitute.org/studies/downloads/ACCU-CHEK_Quick_Reference_Guide.pdf.
American Diabetes Association. Practical Insulin. 3rd ed. 2011:1-68.
DebbieHinnen,ARNP,BCADM,CDE,FAAN,FAADE
DirectorofEducationServices
MidAmericaDiabetesAssociates
Wichita,Kansas
Educational
Barriers
Didnotinitiate(n=69)
6monthsafterinsulininitiation
Beforeinsulininitiation
a
QOL
Physical complaints
Social worries
Hypoglycemia
a
b
Fear of hypoglycemia
Dietary restrictions
Daily struggles
Too painful
10
20
30
40
50
60
40
60
80
100
20
Educatepatientsfromthebeginningofthediseaseprocess
about
Strategiestohelpyoucommunicatethiscriticalinformation
withlimitedtime:
Utilizethediabetesteamtodeliver/reinforceyourmessages
TheprogressivenatureofT2DM
Nursingassistantscansafelyteachinsulinuseandtitration
Diabeteseducatorsandcomprehensiveeducationcanhelpwith
Thecomplicationsassociatedwithpoorglycemiccontrol
Theshort andlongtermeffectsofimprovedglycemiccontrol
initiationandtitrationofinsulin,hypoglycemiaawareness,and
glucagonuse
Avoidthreateningpatientswithinsulintherapy
Considergroupvisits
Useasimpleinsulinregimentostart
Often,820patientscanbeseenatgroupvisits
Reimbursedbythirdpartypayors
Allowpatientstoparticipateintheirinsulindosetitration
Developorobtaincomprehensivehandoutsforpatientsand
reinforceeducationinsmallamountsateachvisit
Patientswhoreceiveeducationabouttheirglycemicgoals
aremorelikelytoacceptinsulintherapy
American Diabetes Association. Practical Insulin: A Handbook for Prescribing
Providers. 3rd ed. 2011:1-68; Cobble M, et al. J Fam Pract. 2009; 58(suppl 11): S7-14.
PATTERN MANAGEMENT
7pointBGprofilescollected
over3days
AACE/ACEtitrationandgoals
recommended
DatausedbypatientAND
provider
Basaldoseadjustment
Initiateat10units/dayat
bedtime
or12unitsevery23
daysuntilFBG goalsmet
Patternmanagementpriorities:
1. Hypoglycemia
2. Fasting/preprandial
hyperglycemia
3. Postprandialhyperglycemia
Abnormalityoccurringon2of3
daysatthesametimeofday
mustbeaddressed
Prandialdoseadjustment
Initiateat5units/meal
or23unitsevery23
daysuntilgoalsmet,
consideringboth2hPBG
andpreprandial BG
Priority3 PostprandialHyperglycemia
7/24
7/25
7/26
PATTERN MANAGEMENT
CASES
10
Hypoglycemia
Date
Fasting
5/12/2010
141
5/14/2010
5/16/2010
51
98
6/6/2010
6/8/2010
81
43
156
146
102
Beforedinner
Afterdinner
79
86
Bedtime
94
133
142
92
115
89
162
93
6/1/2010
6/3/2010
151
101
77
5/28/2010
5/30/2010
Afterlunch
82
109
72
88
5/23/2010
5/26/2010
Beforelunch
68
96
5/18/2010
5/21/2010
Afterbreakfast
65
76
89
163
123
116
183
87
100
162
68
67
82
122
109
84
73
87
212
74
108
72
75
Postprandial Hyperglycemia
Elective 2:
Premixed/Biphasic Insulin Therapy
JavierMorales,MD
St.FrancisHospital
AdvancedInternalMedicineGroup
NewHydePark,NewYork
11
Glargine (n = 1046)
10
A1C (%)
ForpatientswithT1DMorT2DM
Requiresconsistentmealtimesandcarbohydratecounting
MayormaynotcausemoreweightgainthanBBT
MayresultinpoorerglycemiccontrolthanBBT
ForpatientswithT2DMtransitioningfrombasalonlyregimens
9.1
9.0
7.2
7.3
8
7
6
Premixed/biphasicinsulindoesnotguarantee reducedA1C
Mayincreaseriskofhypoglycemia
Baseline
Maycausemoreweightgain
Week 24
OADskeptatbaselinedose(s)throughoutthestudy
A1Cgoalsweremaintainedamedianof16.8monthswith
lispro 75/25and14.4monthswithglargine (P =.04)
11
Randomized Population
A1C = 9.7 1.5% 9.8 1.4%
n=
117
116
Baseline
A1C > 8.5%
Baseline
A1C 8.5%
89
28
99
Detemir-aspart
17
Patients Meeting
Target (%)
0
0.4
0.8
1.2
1.6
2.0
2.4
70
60
50
40
30
20
10
0
60
50
A1C 7%
2.8
4.4
4.8
1.21
1.42
1.69
P =.0129
Minorhypoglycemiaoccurredin31%ofpatientsinthedetemiraspart
groupand28%inthebiphasicaspart group
Weightgainwassimilarinbothgroups(2.4kgvs 2.1kg)
4.0
0.75
1
1.5
P =.106
Glargine
3.6
Previously
TreatedWith
BasalInsulin
0.5
Biphasicaspart 70/30
3.2
InsulinNaive
0
MeanA1CReduction
Frombaseline(%)
AACE
Product
Administerat2largestmealstwicedaily
ORadministeratlargestmealoncedaily
Adjustprebreakfast dosebasedonpredinner glucoselevel
Adjustpredinner dosebasedonprebreakfast (fasting)glucoselevel
Onset(h)
Peak(h)
EffectiveDuration (h)
HumanBiphasic Insulin
Hirschetal(2005)
70%NPH/30%regular
Transitioningfromoncedailybasalinsulintotwicedailypremixed/biphasic:
DivideTDDby2tocomputethedoseofeachinjection(beforebreakfastanddinner)
Ifmealsarenotofequalsize,largermealrequiresalargerproportionofinsulin
AdjustdosesaccordingtoSMBGanddiethistory
ReduceTDDby20%ifthereisrecurrenthypoglycemia
0.51
Dual
1016
Analogue BiphasicInsulin
INITIATE
Beginat10units/dayifFPG<180mg/dL
ORbeginat12units/dayifFPG180mg/dL
BeginwithTDDequallydividedbetweenbreakfastanddinner
Administerdoses015minutesbeforemeals
Adjustaccordingtotitrationscheduleshowninbackofprogrambook
Handelsman Y, et al. Endocr Pract. 2011;17(suppl 2):1-53.
Hirsch IB, et al. Clin Diabetes. 2005;23(2):78-86.
Raskin P, et al. Diabetes Care. 2005;28(2):260-265.
75%NPL/25% lispro
<0.25
Dual
1016
50%NPL/50%lispro
<0.25
Dual
1016
70%aspart protamine/
30% aspart
<0.25
Dual
1518
Elective 3:
Insulin Therapy in T1DM
Preparation
Mustberolledand/ortipped(NOTSHAKEN)for20cycles
EtieMoghissi,MD,FACP,FACE
Siteselection
ClinicalAssociateProfessor
UniversityofCalifornia,LosAngeles
LosAngeles,California
Considerationmustbegiventoinjectionsitewhenusingmixes
containingNPH
AMinjectionisbestgivenintheabdomenbecauseofmorerapid
absorption(coverageforbreakfast)
PMinjectionshouldbegiveninthebuttocksorthighbecauseof
slowerabsorption(preventionofnocturnalhypoglycemia)
12
Correctionor
Supplemental
insulin
Insulin
GlycemicvariabilitytendstobegreaterinpatientswithT1DM
thaninT2DMpatientstreatedwithinsulin
TheoccurrenceofhypoglycemiaisgreaterinT1DMpatientsthan
T2DMpatients
NormalSecretory
PatternofInsulin
T1DMdemandsbasal+multipleprandialinsulininjections/day
Basalinsulin
ExpertsrecommendSMBG measurements3timesdailyin
individualswithT1DM
Breakfast
Lunch
Dinner
Bedtime
Obtainpatientweightinkg
Calculatetotaldailydose(TDD)
as0.20.4U/kg/daya
Basal
Analogues
Prandial (Nutritional)
Analogues
Insulinglargine
Insulindetemir
Insulin aspart
Insulinglulisine
Insulinlispro
Human
Human
NPH
Regular
Choosethedosingschedule
Give50%ofTDDasbasalinsulin
Give50%ofTDDasbolus(premeal )insulin
Adjustaccordingtoresultsof
BGmonitoring
a
WeightedMean
Difference(95%CI)
Interpretation
Treatment
A1C
0.08 (0.12to0.04)a
Favorsanalogues
Fastingplasmaglucose
0.63(0.86to0.40)a
Favorsanalogues
Fastingbloodglucose
0.86(1.00to0.72)a
Favorsanalogues
Weightgain
0.67(0.87to0.45)a
Favorsanalogues
Hypoglycemia
OddsRatio(95%CI)
Interpretation
Any
0.93(0.8 to1.08)
Equivalent
Severe
0.73(0.61 to0.87)a
Favorsanalogues
Nocturnal
0.70(0.63 to0.79)a
Favorsanalogues
a P < .05.
Results based on 23 studies in adults with T1DM, 3872 on basal
insulin analogues, 2915 on NPH insulin.
Trials
(N)
AdultsWith
T1D(N)
ChangeinA1C
%(95%CI)
Interpretation
Aspart
3035
0.13(0.20to0.07)a
Favorsanalogue
Lispro
22
6021
0.09(0.16to0.02)a
Favorsanalogue
SevereHypoglycemia
RelativeRiskRatio
%(95%CI)
Interpretation
Treatment
Trials AdultsWith
(N)
T1D(N)
Aspart
1814
0.83(0.65to1.04)
Equivalent
Lispro
10
4502
0.80(0.67to0.96)a
Favorsanalogue
a P < .05.
Glulisine was not licensed in Canada during
the period covered by the analysis.
13
Upto40%ofT1DMpatientsintheUSutilizecontinuoussubcutaneous
insulininfusion(CSII)1,2
CSII usesrapidactinginsulintodeliverbothbasalandbolustherapy1
3500
16
Lispro
14
NPHinsulin
RHI
Insulinglargine
RateofHypoglycemia
(Events/100PatientYears)
FrequencyofMildHypoglycemia
(Episodes/PatientMonth)
12
10
8
6
4
AdvantagesofpumptherapyinT1DMinclude:1,2,3,4,5
3000
2500
2000
CSII canbepairedwithcontinuousglucosemonitoring(CGM):4,5
Toprovidemorefrequentglucosereadings
Toreducetheincidenceofhypoglycemia
1500
2
0
CGM doesnotreplaceSMBG3
1000
5.5
6.0
6.5
7.0
7.5
Improvedglycemiccontrol
Areductioninhypoglycemia
Improvedqualityoflife
Reducedfrequencyofdiabeticketoacidosis
6.0
8.0
7.0
A1C(%)
8.0
9.0
10.0
A1C(%)
1. Handelsman Y, et al. Endocr. Pract. 2011;17(suppl 2):1-53; 2. Pickup J, et al. Int J Clin Pract. 2011;65:16-19
3. Hinnen D, Tomky D. In: Mensing C, et al, eds. The Art and Science of Diabetes Self-Management: A Desk
Reference for Healthcare Professionals. 2011:531-576; 4. Blevins T, et al. Endocr Pract. 2010;16:730-745;
5. Klonoff D et al. J Clin Endocrinol Metab. 2011;96:2968-2979
Motivatedtoimproveglycemiccontrol
Intellectuallyandphysicallyabletomanageinsulin
pumptherapy
SimilarlytoT2DM,insulinanaloguesarepreferredinthe
treatmentofT1DMduetotheirmorephysiologicprofile
ExperiencewithfrequentSMBG
Thetimeactionprofilesofinsulins maydifferinindividuals
withT1DMcomparedtoT2DM
Fluentincarbohydratecountingandinsulincorrection
InsulintherapyconsiderationsdifferforpatientswithT1DM
andpatientswithT2DM
Insulinpumptherapycancontributetoimprovedglycemic
controlandlesshypoglycemiainT1DM
Willingnesstocommunicatewiththediabetesteam
Insulinpumptherapyrequiresamotivated,compliant
patientwillingtocommunicatewiththediabetesteam
NewInsulinCombinations
Insulin+DPP4inhibitors
Insulin+GLP1receptoragonists
EtieMoghissi,MD,FACP,FACE
InvestigationalInsulins
ClinicalAssociateProfessor
UniversityofCalifornia,LosAngeles
LosAngeles,California
Limitationsofcurrentinsulins andfutureneeds
Investigationalbasalinsulins
Investigationalprandialinsulins
* Some of the agents and/or combinations to be discussed are not US FDA-approved at this time.
14
Approvedforuseincombinationwithinsulin1
Saxagliptin
Approvedforuseincombinationwithinsulin1
Notapprovedforuseincombinationwithinsulin1
Linagliptin
Clinical trialsinprogress2
0.0
0.2
0.4
0.6
0.6
0.8
P <.001
Sitagliptin
INSb +SAXA(n=304)
INSb +PBO(n=151)
24weektrial
0.0
Approval StatusforCombinationwithInsulin
MeanA1Cfrom BL (%)
Agent
INSa +SITA(n=322)
INSa +PBO(n=319)
1.0
a
10
5
0
52weektrial
INSb +SAXA(n=304)
INSb +PBO(n=151)
24weektrial
1.0
15
1.0
0.8
0.6
0.4
0.2
52weektrial
0.8
0.6
0.5
0.4
0.2
0.1
0.1
0.0
0.0
0.8
Difference=0.4
(95%CI,0.6to0.2)
0.8
0.8
INSa +SITA(n=322)
INSa +PBO(n=319)
20
10
0.4
0.6
BodyWeight(kg)
16
15
ConfirmedHypoglycemia
(%ofPatients)
SymptomaticHypoglycemia
(%ofPatients)
P =.003
20
25
0.4
INSb +SAXA(n=304)
INSb +PBO(n=151)
24weektrial
25
0.2
1.0
BodyWeight(kg)
INSa +SITA(n=322)
INSa +PBO(n=319)
52weektrial
Agent
Approval StatusforCombinationwithInsulin
0.0
1.5
Liraglutide
Exenatide QW
A1C(%)
ExenatideBID
Notyetapprovedincombinationwithinsulin
NDAfiledin2011 awaitingresponsefromtheUSFDA2
approvedincombinationwithinsulin1
Notyet
Clinicaltrialsinprogress3
1.0
1.0
1.5
2.0
Weight (kg)
1
0.5
Approvedincombinationwithinsulinglargine1
0.5
0
0.5
1
1.5
1.7
1.8
P < .001
SimilarratesofminorhypoglycemiainEXNBID(25%)andPBO(29%)groups
1. US FDA. Drugs@FDA Web site. http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA/;
2. Reuters. 2011. http://uk.reuters.com/article/2011/06/28/novonordisk-idUKLDE71F09U20110628;
3. US National Institutes of Health. http://www.clinicaltrials.gov/ct2/home.
More discontinued due to AEs in EXN BID (9%) vs PBO (1%) group (P < .01).
15
Studyonorderofaddition
(chartreview,24motreatment)
0.0
TreatmentPeriod
(Weeks052)
0.10
Runin:Weeks12to0
1.8mgLIRA+MET
PatientsnotachievingA1C<7%
randomizedtostudytreatments
0.7
a
1.0
A1CChange(%)
A1CChange(%)
0.01
0.00
0.5
1.0
a
1.5
0.20
0.30
Weightdecreasedsignificantly(2.5kg)intheEXNBIDaddedtoGLARgroupa
0.50
0.50
MET+LIRA1.8mgcontrol
(n=161)
MET+LIRA1.8mg+insulindetemir
(n=162)
0.40
2.0
Study+extension:Weeks0to52
26weekstudy+26week
extension
Addedinsulindetemir ornothing
MeanstartingA1C=7.6%
0.10
P <.0001
Levin PA, et al. Endocr Pract [published online ahead of print July 8, 2011]:1-28.
1920
1930
1940
Insulindetemir
approvedinUS
(2005)
Recombinanthuman
insulindeveloped
(1979)
NPHinsulin
developed(1946)
InvestigationalInsulins
Insulinlisproapproved
inUS(1996)
Synthetichuman
insulindeveloped(1965)
Insulindiscovered(1921)
1950
1960
1970
1980
Inhaledinsulin
developed(2006)
1990
2000
2010
Investigationalbasalinsulins
Investigationalprandialinsulins
Insulinpen
developed(1981)
Lente(zinc)insulins
developed(1952)
Insulinaspartand
insulinglargine
approvedinUS(2000)
Firsthumantreatment
withbovineinsulin(1922)
Tattersall RB. In: Pickup JC, Williams G, eds. Textbook of Diabetes. 3rd ed.
Blackwell Science: Malden, MA; 2003:1.1-1.22; Drugs@ FDA;
http://diabetes.webmd.com/news/20071018/pfizer-quits-inhaled-insulin-exubera.
Withdrawn.
Subject231
8 12 16 20 24
ElapsedTime(hours)
InsulinActionProfilesforClinicallyRelevantDosesinPatientsWithT2DMa,b
Subject214
4 8 12 16 20 24
ElapsedTime(hours)
GlucoseinfusionRate
(mg/kg/min)
Glargine
7
6
5
4
3
2
1
0
NPH
GIRtoMaintainConstant
BGLevel(mg/kg/min)
GIRtoMaintainConstant
BGLevel(mg/kg/min)
GIRtoMaintainConstant
BGLevel(mg/kg/min)
Detemir
7
6
5
4
3
2
1
0
Subject215
3.0
Detemir(0.4U/kg)
Glargine(0.4U/kg)
2.5
Detemir(0.8U/kg)
Glargine(0.4U/kg)
2.0
1.5
1.0
0.5
0
0
10
12
14
16
18
20
22
24
Time(h)
8 12 16 20 24
ElapsedTime(hours)
a
N = 54 T1DM patients.
Euglycemic glucose clamp study, 4 trials/subject.
Insulinglulisine
approvedinUS
(2004)
Insulinpump
developed(1978?)
Protamineandprotamine
zincinsulinsdeveloped(1936)
16
Injectiontimeandfrequencyof
insulinglargineinT1DM(n=292)
Morning
21%
Evening
43%
Insulin
Administration
Status
Peak
Effective
Duration
Approved
outside US
3h
24 h
Once daily,
thrice weekly
Filed for
approval
Peakless
> 24 h
Degludec (NN1250)4-6
a
b
GlucoseInfusionRate
(mg/kg/min)
Phase2trial
0.8units/kg
0.6units/kg
0.4units/kg
5
4
16weeks
DEG(n=61)vs GLAR
(n=62),allreceivingOADs
BLA1C:8.6% 8.7%
3
2
SimilarA1Cchanges
16
12
20
DEG
15
5
1.1
0
Confirmed
Overall
GLAR:1.5%
24
GLAR
10
0.6
DEG:1.3%
HypoglycemiaRate
(events/pty)
Twice
daily
36%
Longdurationofaction
Lowriskofhypoglycemia
0.1
Nocturnal
Time(h)
a Degludec
50
A1C:1.2%1.3%
PatientsAttainingA1C<7%
15
11.1
10
P =.04
1.4 1.8
40
Nocturnal
40
P =NS
43
30
20
10
0
0
Confirmed
Overall
GLAR
P =NS
50
13.6
Patients(%)
P =NS
50
DEG
BLA1C:7.7%
P =.04
HypoglycemiaRate
(events/pty)
Patients(%)
60
50
40
30
20
10
0
A1C:0.4%0.4%
PatientsAttainingA1C<7%
HypoglycemiaRate
(events/pty)
DEG
BLA1C:8.3%
50
40
42.5 40.2
30
20
P =.021
4.4 5.9
10
0
Confirmed
Overall
Nocturnal
17
GIR(mg/min/kg)
ILPS(0.8U/kg;n=28)
DET(0.8U/kg;n=32)
GLAR(0.8U/kg;n=29)
InvestigationalInsulins
Investigationalprandialinsulins
1
0
0
10
12
14
16
18
20
22
24
Time(hours)
70
60
50
40
30
20
10
0
Time (min)
Rapidonset
Quickpeak
Insulin Glulisine
140
80
Shortdurationofaction
Lowriskofhypoglycemia
120
60
Insulin, IU/mL
80
Insulin Aspart
Insulin Lispro
40
20
100
Clinical
Trial Phase
Peak
Effective
Duration
With meals
45-120 min
<5h
With meals
30-90 min
<5h
80
60
40
20
Administration
Insulin
0
0
60
120 180
Time (min)
Naturallyoccurringspacefilling
gellikesubstance
Anaturallyoccurringenzyme
Majorcomponentofnormalsoft
connectivetissuesuchasskin
Temporarilydegradeshyaluronan
andfacilitatespenetrationof
drugsattheinjectionsite
Lispro
Lispro+rHuPH20
RHI
RHI+rHuPH20
1500
Naturalandsynthetic
hyaluronidase formulationsare
available
USFDAapprovedasadjuvantsto
increasethedispersionand
absorptionofinjecteddrugs
250
1250
200
1000
150
750
100
500
50
250
0
Transientlocallyactingpermeation
enhancers
60
120
180
240
300
Mean( SEM)
ImmunoreactiveInsulin(U/mL)
Hyaluronan
Mean( SEM)
ImmunoreactiveInsulin(pmol/L)
0
360
18
DEG 70%/ASP30%(0.57U/kg)(n=61)
DegludecPlus
Inhaled insulin
Once daily
Peak
Thrice daily
Efficacy(TreattoTargetDesign)
Yes
10-16 min
> 24?
1.0
1.5
2.0
2.5
BLA1C:8.5%8.6%
0.5
60-120 m
3.0
Hypoglycemia
15
0.5
0.0
filed for
approval
BIASP 70/30(0.66U/kg)(n=62)
EventRate(EPY)
Administration
Effective
Duration
A1C(%)
Insulin
Clinical
Trial
Phase
1.8
10
P <.05
7.3
5
2.9
1.9
ProportionwithA1C<7%
withouthypoglycemia:
67% 40%
0.4
1.1
0
Confirmed
Hypo
Nocturnal
Severe
52weeknoninferioritytrial
IHP(n=323);9%withdrewduetoAEs(P <.05vs BIASP)
BIASP(n=331);4%withdrewduetoAEs
SimilarA1Cchanges
Investigationalbasalinsulinanalogueshavethe
potentialtoimproveinsulintherapybyproviding
relativelypeakless timeactionprofilesandlowerrates
ofhypoglycemia
IHP:0.59%
BIASP:0.71%
SignificantlyfewerhypoglycemiceventswithIHP
IHP:0.41eventsperpatientmonth
BIASP:0.61eventsperpatientmonth
Prandialinsulins withmorerapidonsetandoffsetthan
currentprandialanaloguesareindevelopment
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