Inisiasi Terapi Diabetes Dengan

Biosimilar Insulin Glargine

Djoko Wahono Soeatmadji

Division of Diabetes Metabolism and Endocrinology

Department of Internal Medicine, Dr. Saiful Anwar Hospital,
Medical Faculty, University of Brawijaya, Malang
Indonesia
 The Paradigm of Type 2 Diabetes
Treatment
Aggressive Treatment Driven by
individual (AIC < 7%)
Early Combinations
- OHA
- OHA Noninsulin parenteral
- OHA - Insulin
Early Insulin Treatment
 Genetic and environmental risk
factors impact inflammation,
autoimmunity, and metabolic stress

Environmental Influences
Dietary factors, endocrine disruptors and
other environmental
polluters, and gut microbiome
composition

Jay S. Skyler,1 George L. Bakris,2 Ezio Bonifacio,3 Tamara Darsow,4 Robert H. Eckel,5
Leif Groop,6 Per-Henrik Groop,7,8,9 et al. Differentiation of Diabetes by Pathophysiology, Natural History,
and PrognosisDiabetes 2017;66:241255 | DOI: 10.2337/db16-0806
 Type 1 Diabetes Multiple hits
and or -cell regeneration
100

-cell
mass
(%)

Fulminant Regular
30 Diagnosis

20 Diagnosis
Diagnosis

10 Diagnosis

Chilhood Adolescemce Adulthood (LADA)

AGE AT DIAGNOSIS

The destruction of -cells and the appearance of type 1 diabetes

according to the age of onset and the putative pathogenetic mechanism
Paolo Pozzilli and Umberto Di Mario. Diabetes Care 2001; 24: 1460-1467
 Disdorders of Gycemia
Etiologic types and Stages
Stages Normoglycemia Hyperglycemia
Normal glucose Diabetes Mellitus
IGT or
Types regulation Insulin requiring
IFG No For control For survival

Insulin requirement +++ +++++

Type 1
Type 2
Other
types

Gestational
diabetes
 Pharmacokinetic of
Endogeneous Insulin Secretion
 Vascular and cellular organization of pancreatic islet
Insulin is directly secreted into hepatic portal vein in response to
increase portal glucose level
Insulin release in vitro
Physiological (normal) insulin and plasma
glucose profiles
9.0
Plasma glucose Peak postmeal
(mmol/L)

7.0

Basal (post absorbtive)

5.0

480
Peak postmeal
Plasma insulin

320
(pmol/L)

160
Basal (post absorbtive)
0
0700 1200 1800 2400 0600
Clock time (h)

Diabetes Care 1999;22:795-800

Pharmacokinetic of Exogenous
Insulin Injected Sucutaneously
Events after subcutaneous injection of soluble regular insulin : concentration of
hexameric insulin are lowered by diffusion in the interstisial spabe allowing
dissociation into dimers and monomers which pass more readily through the
capillary membrane (Lee and Zinman,1998)
 50
Comparison of change Non-diabetic insulin
response to mixed meal
in the plasma insulin
concentration in 40

response to a mixed

Plasma insulin (mU/L)

meal in non-diabetic
30
subjects, with changes
in free insulin
concentration after a SC short-acting
20
insulin in
typical subcutaneous type 1 diabetes

(SC) dose of short-

10
acting insulin in a type
1 diabetic patient
0
0 1.0 2.0 3.0 4.0 5.0 6.0 7.0 8.0
Time (min)

Biotechnology of Insulin Therapy. Oxford: Blackwell Scientific Publications, 1991;1-23

The time course of the action of regular insulin,
premixed insulin and neutral protamine
Hagedorn (NPH) insulin
11
Glucose infusion rates (mg/kg/min)

10
9 Regular insulin
8
7
6 25/27-premixed insulin
5
4
NPH insulin
3
2
1
0
0 120 240 360 480 600 720 840 960 1080 1200 1320 1440
Time (min)
Diabetes Stoffwech 1996;5:157-63
Properties of Ideal Exogenous Insulin
Rapid-acting insulin
Onset of action < 0.5 after SC injection
High peak activity
Duration of action < 4 h

Long-acting insulin
Onset of action > 4 h after SC injection
Duration of action 24 h (one injection per day)
No pronounced peak activity
Almost constant action over time

General
Small intra-individual variability of insulin action
Metabolic effect greater than mitogenic effects
No significant immunogenic effects
Chemically stable
No problem with miscibility
 INSULIN ANALOGS

Modified structure of the human insulin

resulting altered physicochemical,
biological, and pharmacological properties
 Modification made to the primary structure
of the insulin molecule in order to obtain
rapid-acting insulin analogues or the long
acting insulin analogue
Amino-acid residus involved in dimerization
Amino-acid residues involved in assembly of dimers into hexamers

A chain * Probable sites of inferaction with receptor

S S
* * * *
Gly lle Val Glu Gln Cys Cys Thr Ser lle Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Asn COOH
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
Insulin
Ala Val glargine
S S
Gly Arg Arg

S S Insulin
glargine
B chain

* * * * *
NH2- Phr Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr Arg Arg
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32
 Glargine
(compared to human NPH)
Receptor interaction : similar
Activation of IGF-1 : slightly higher
Pharmacokinetics and dynamics :
peakless (50% lower)
duration of activity 2-fold longer
Immunogenicity (animal) : less than NPH
human
Mitogenicity (animal) : equal

The True Basal 24 hours duration of action -

Peakless Insulin Analog
 Response rates at endpoint
HbA1c < 7.5% without nocturnal
hypoglycemia (FAS)

p=0.0174

30
22.9
25
% of patients

20
14.0
15
10
5
0
Insulin glargine NPH insulin

LEAD Study Investigator Group. Diabetes Research and Clinical Practice 2006. DOI:
10.1016/j.diabres 2006.08.012
When to start insulin ? Which insulin ?
 The Paradigm of Type 2 Diabetes
Treatment
Aggressive Treatment Driven by
individual (AIC < 7%)
Early Combinations
OHA
OHA Noninsulin parenteral
OHA - Insulin (basal insulin)
Early Insulin Treatment
OHA: oral hypoglycaemic agent
 ADA/EASD consensus algorithm
Tier 1: Call to action if HbA1c is 7%
well-validated therapies
Lifestyle + Metformin Lifestyle + Metformin
+ Basal insulin + Intensive insulin
At diagnosis:
Lifestyle +
Metformin
Lifestyle + Metformin
+ Sulfonylurea

STEP 1 STEP 2 STEP 3

Tier 2:
Less well validated Lifestyle + Metformin
therapies + Pioglitazone Lifestyle + Metformin
No hypoglycaemia + Pioglitazone
Oedema/CHF + Sulfonylurea
Bone loss

Lifestyle + metformin
+ GLP-1 agonist Lifestyle + metformin
No hypoglycaemia + Basal insulin
Weight loss
Nausea/vomiting
25
Nathan DM, et al. Diabetes Care 2009;32 193-203.
 Insulin-based treatments
Start insulin therapy for adults with type 2 diabetes from a
choice of a number of insulin types and regimens:
Offer NPH insulin injected once or Consider, as an alternative to NPH
twice daily according to need insulin, using insulin detemir or
Consider starting both NPH and insulin glargine:
short-acting insulin if the person's - because of significant
HbA1c is 75 mmol/mol [9.0%] or
hypoglycaemia on NPH
higher) either seperately or as a
premixed (biphasic) insulin
- long-acting insulin analogues
would reduce the number of
daily injection

Type 2 diabetes in adults: management NICE guideline NICE

Published: 2 December 2015 nice.org.uk/guidance/ng28
 American Diabetes Association
Standards of Medical Care in Diabetes 2017

ADA. Standard of Medical Care. Diabetes Care, January Suppl. 1, 2017

 When to start insulin ? Which insulin ?

If oral agents failed to achieved target glycaemic control

Start with Insulin basal
Generic Drugs and Biosimilar
 Confusion of Terms
The United States: Follow-on biologics or FoBs/follow-on proteins
or FOPs)
Canada: Subsequent entry biologic or SEB
WHO guidance: Reference biotherapeutic products (RBP)
Australia: Similar biological medicinal products (SBMPs)
the European Union: Biosimilars
Biopharmaceuticals (drug products that contain biotechnology-
derived proteins as active pharma-ceutical ingredients)
Biopharmaceutical products not subject to regulatory approval or B-
NSRA
Bioidenticals. Same product sold under different brand names by
different companies

Lutz Heinemann and Marcus Hompesch. Biosimilar Insulins: How Similar is Similar?
J Diabetes Sci Technol 2011;5(3):741-754
 A Brief History of Patents on Insulin
Insulin was first extracted from whole animal pancreas in
1921, by Frederick Banting and Charles Best
The first patient was treated in 1922
Patent application on the insulin isolated by Banting and
Best was delayed until 1923
Sold to the University for $ 1 US
Glargine (R/ lantus) patent expired in 2015
Insulin is an essential medicine that is needed for all people with type 1 diabetes, and a
growing number of people with type 2 diabetes. It is crucially important that people in
need can access this life-saving medicine

Published by Health Action International

Overtoom 60 (2) | 1054 HK Amsterdam The Netherlands | +31 20 412 4523 www.haiweb.org
Andrew W. Mulcahy, Zachary Predmore, and Soeren Mattke. The Cost Savings Potential of Biosimilar Drugs in
the United States. Perspective. Rand Corporation
 Biosimilars will lead to a $44.2 billion
reduction in direct spending on biologic
drugs from 2014 to 2024, or about 4 percent
of total biologic spending over the same
period, with a range of $13 billion to $66
billion.

Andrew W. Mulcahy, Zachary Predmore, and Soeren Mattke. The Cost Savings Potential of Biosimilar Drugs in
the United States. Perspective. Rand Corporation
Copyright 2014 RAND Corporation. www.rand.org
Comparative Molecular Weight
Small Molecule Drugs (SMDs) vs Biologic
 Comparison of Traditional Molecule Drugs and
Biologic Agents
Feature Small Molecule Drug Biologic Agent

Example Acetylsalicylic avid Monoclonal antibody

(180 Da) (150 000 Da)
Entity Chemical Protein
Structure Small, simple, well characterized Large, complex, heterogeneous
Stability Stable Unstable
Mode of Usually amendable to ingestion Usually requires injection or
administration infusion
Manufacturing Predictable and precise method; Living cell-based complex
process identical copy in batches technolofy; batch to batch
variation, sensitive to storage and
handling
Immune genecity Mostly nonimmunogenic Immunogenic
 Cloning and Protein Expression

Protein Production, Purification and Validation

 Analytically Differences Between an Innovator Product and a
Biosimilar batch-to-batch consistency, product stability alongside
clinical safety and efficacy
Seshiah V, Das AK, Sethi BK, Moses CRA, Kumar A, Viswanathan V, Joshi SR, Balaji V, Sahay RK, Kalra S, Saboo
B, Singh AK, Ghosal S, Zargar AH, Muruganathan A. Biopharmaceuticals and Biosimilars: A Consensus
Statement, 2009
Requirements of the Biologic Parts Price Competition and
Innovation Act 2009
Lilly Insulin (Biosimilar) Glargine :
Basaglar
 The amino acid sequences of Lilly Insulin
Glargine*and reference product** are identical
S S

Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Gly

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

S
S INSULIN GLARGINE (BASAGLAR)
S
S
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr Arg Arg

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32

S S

Gly Ile Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu Glu Asn Tyr Cys Gly

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21

S
S
INSULIN GLARGINE (Lantus)
S
S
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Thr Arg Arg

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32

1. Lantus prescribing information. Revised October 2013;

2. EMA. Assessment Report. 2014
*insulin glargine (basaglar kwikpenTM)
**insulin glargine (lantus)

42
 INSULIN GLARGINE (BASAGLARTM) has
been evaluated in a comprehensive
clinical trial program The totality of evidence

Phase III studies1,2

STUDY DETAILS ELEMENT 1 ELEMENT 2

T1DM T2DM

Phase I studies3
PK / PD of Insulin Glargine
(BASAGLARTM) versus
reference insulin glargine*

Preclinical studies
Biochemical and physicochemical characterization

1. Blevins TC et al. Diabetes Obes Metab 2015;17:72633

2. Rosenstock J et al. Diabetes Obes Metab 2015;17:73441
*reference insulin glargine refers to Insulin Glargine (Lantus) 3. Linnebjerg et al. Diabetes Care 2015;38:222633
PD, pharmacodynamic; PK, pharmacokinetic .

45
 Pharmacokinetic (PK)
and
Pharmacodynamic (PD)
 The Lillys Insulin glargine
pharmacokinetic (PK) profile is similar
to that of reference insulin glargine 200
LILLY INSULIN GLARGINE (BASAGLAR)
reference insulin glargine*
insulin concentration SD (pmol/L)

150
Mean C-peptide-corrected

100

50

0
0 6 12 18 24
Time (hours)
Study ABEO (Phase I) in healthy individuals1
SD, standard deviation 1 Linnebjerg H et al. Diabetes Care 2015;38:222633
* reference insulin glargine is Insulin glargine (Lantus )

47
 The Lillys Insulin glargine pharmacodynamic
(PD) profile is similar to that of reference insulin
glargine
8
INSULIN GLARGINE (BASAGLAR)

reference insulin glargine*

6
Mean glucose infusion rate SD
(mg/kg/min)

0
0 4 8 12 16 20 24
Time (hours)
Study ABEO (Phase I) in healthy individuals1
* reference insulin glargine is Insulin glargine (Lantus) 1 Linnebjerg H et al. Diabetes Care 2015;38:222633

48
Efficacy
 Lillys Insulin glargine and reference insulin glargine provide
similar HbA1c reductions in T1DM patients

LILLYS INSULIN GLARGINE (BASAGLAR) reference insulin glargine*

KEY FINDINGS
Baseline Baseline
HbA1c (%), HbA1c (%),
mean SD 7.8 1.1 7.8 1.0 mean SD 7.8 1.1 7.8 1.0

n=268a n=267a n=268a n=267a

0.00 0.00

0.26 0.28
-0.25 0.35 -0.25
0.46
Change in HbA1c SE (%)

Change in HbA1c SE (%)

-0.50 -0.50

-0.75 -0.75

-1.00 -1.00
Week 24 Week 52
=0.108 =0.020
95% CI (0.002 to 0.219) 95% CI (0.099 to 0.140)
P=ns P=ns
Study ABEB (Phase III; open-label) at Week 241
aFull analysis set; numbers reflect maximum sample size

HbA1c, glycosylated hemoglobin; ns, not significant; SE, standard error

* reference insulin glargine is Insulin glargine (Lantus) . 1. Blevins TC et al. Diabetes Obes Metab 2015;17:72633

50
 Lillys Insulin glargine and reference insulin glargine provide
similar HbA1c and FBG reductions in T2DM
LILLYS INSULIN GLARGINE (BASAGLAR) reference insulin
glargine*
KEY FINDINGS Baseline
HbA1c (%), FBG (mg/dL),
mean SD 8.3 1.1 8.3 1.1 mean SD 159 45 160 44

n=376a n=380a n=376a n=380a

0.0 0

-10

Change in FBG SE (mg/dL)

Change in HbA1c SE (%)

-0.5 -20

-30
46
48
-1.0 1.29 -40
1.34

-50

-1.5 -60
=0.052 =0.28 1.04
95% CI (0.07 to 0.18) P=ns
P=ns
Study ABEC (Phase III; double-blind) at Week 241
aFull analysis set; numbers reflect maximum sample size

* reference insulin glargine is Insulin glargine (Lantus)

1. . Rosenstock J et al. Diabetes Obes Metab 2015;17:73441
51
 Lillys Insulin glargine and reference insulin
glargine provide similar FBG control in T1DM
KEY FINDINGS
FBG (mg/dL)

INSULIN GLARGINE reference insulin

(BASAGLAR) glargine* P value
(n=268a) (n=267a)

Baseline SD 151 54 147 54 ns

Week 24 SE 144 4 141 4 ns

Week 52 SE 145 4 149 4 ns

Study ABEB (Phase III; open-label) at Week 241

aFull analysis set; numbers reflect maximum sample size

FBG, fasting blood glucose

* reference insulin glargine is Insulin glargine (Lantus) 1. Blevins TC et al. Diabetes Obes Metab 2015;17:72633

52
Weight change and total daily insulin dose are similar
with Lillys Insulin glargine and reference insulin
glargine in T1DM
Body weight (kg)
INSULIN GLARGINE reference insulin
(BASAGLAR) glargine* P value
(n=268a) (n=267a)
Baseline SD 76 17 75 15 ns
Change at Week 24 SEb 0.4 0.2 0.1 0.2 ns

Insulin dose SE (U/kg/day)

INSULIN GLARGINE reference insulin
(BASAGLAR) glargine* P value
(n=268a) (n=267a)
Baseline SD
Basal 0.33 0.14 0.31 0.13 ns
Prandial 0.40 0.19 0.40 0.22 ns
Week 24 SE
Basal 0.37 0.01 0.36 0.01 ns
Prandial 0.35 0.02 0.35 0.02 ns

Study ABEB (Phase III; open-label) at Week 241

aFull analysis set; numbers reflect maximum sample size;
bChange from baseline to Week 24 1. Blevins TC et al. Diabetes Obes Metab 2015;17:72633
* reference insulin glargine is Insulin glargine (Lantus) 2. Blevins et al. ADA 2014:69-OR

53
Weight change and mean daily insulin dose are similar with
Lillys Insulin glargine and reference insulin glargine in T2DM

Body weight change (kg)

INSULIN GLARGINE reference insulin
(BASAGLAR) glargine* P value
(n=376a) (n=380a)
Baseline SD 90 20 90 19 ns

Change at Week 24 SEb 1.8 0.3 2.0 0.3 ns

Mean daily insulin dose SE (U/kg/day)

INSULIN GLARGINE reference insulin

(BASAGLAR) glargine* P value
(n=376a) (n=380a)

Baseline 0.16 0.01 0.14 0.01 ns

Week 24 0.50 0.03 0.48 0.03 ns

Study ABEC (Phase III; double-blind) at Week 241

aFull analysis set; numbers reflect maximum sample size;
bChange from baseline to Week 24 1. . Rosenstock J et al. Diabetes Obes Metab 2015;17:73441
* reference insulin glargine is Insulin glargine (Lantus) 2. Hollander et al. EASD 2014;948

54
 HbA1c reductions in T2DM insulin-nave patients and in T2DM patients
previously treated with reference insulin glargine

KEY FINDINGS LILLYS INSULIN GLARGINE (BASAGLAR) reference insulin

glargine*

All Insulin-nave Prior reference insulin glargine*

0.0 n=376a n=380a n=220a n=235a n=155a n=144a
Change from baseline in HbA1c SE

-0.5
1.02 1.01

1.29
(%)

-1.0 1.34
1.48 1.54

-1.5

-2.0
= 0.052 = 0.061 = 0.004
95% CI (0.07 to 0.18) 95% CI (0.09 to 0.21) 95% CI (0.19 to 0.19)
P=ns P=ns P=ns
Study ABEC (Phase III; double-blind) at Week 241
aFull analysis set; numbers reflect maximum sample size

* reference insulin glargine is Insulin glargine (Lantus) 1. . Rosenstock J et al. Diabetes Obes Metab 2015;17:73441

55
Safety Profile
 The safety profiles of Lillys Insulin glargine and
reference insulin glargine are similar in patients with
T1DM and T2DM
T1DM1 T2DM2

reference reference
INSULIN GLARGINE INSULIN GLARGINE
insulin insulin
AEs, n (%)a (BASAGLAR) (BASAGLAR)
glargine* glargine*
(n=268b) (n=376b)
(n=267b) (n=380b)

Deaths 0 1 (<1) 1 (<1) 1 (<1)

SAFETY Serious AEs 20 (8) 24 (9) 15 (4) 18 (5)

Discontinuations due to an AE 2 (1) 6 (2) 6 (2) 11 (3)

Injection site AEs 7 (3) 3 (1) 13 (4) 11 (3)

AEs 167 (62) 166 (62) 196 (52) 184 (48)

Possibly related to study drug 17 (6) 14 (5) 26 (7) 23 (6)

Possibly related to study procedure 2 (1) 2 (1) 6 (2) 8 (2)

Possibly related to study disease state (diabetes) 21 (8) 16 (6) 19 (5) 18 (5)

Special topic assessment of allergic reactions 20 (8) 11 (4) 21 (6) 27 (7)

Studies ABEB (Phase III; open-label) over 52 weeks1 and ABEC (Phase III; double-blind)
over 24 weeks2; P>0.05 for all treatment comparisons1,2
aPatients may be counted in >1 category; bFull analysis set; numbers reflect maximum

sample size; AE, adverse event 1. . Blevins TC et al. Diabetes Obes Metab 2015;17:7263
* reference insulin glargine is Insulin glargine (Lantus) 2. . Rosenstock J et al. Diabetes Obes Metab 2015;17:73441

57
 The rate of hypoglycemia is similar with Lillys insulin
galrgine and reference insulin glargine in patients with
T1DM and T2DM
LILLYS INSULIN GLARGINE (BASAGLAR) reference insulin
glargine*
T1DM1 T2DM2
175 175
P=ns P=ns P=ns P=ns P=ns P=ns
Events/patient /1 year, mean SD

Events/patient /1 year, mean SD

140 140
SAFETY

105 105

70 70
80
77

35 35
<1 <1 <1 <1
16 17 21 22 8 8
0 0
All Nocturnal Severe All Nocturnal Severe
n=268a n=267a n=268a n=267a n=268a n=267a n=376a n=380a n=376a n=380a n=376a n=380a
Studies ABEB (Phase III; open-label) at Week 521 and ABEC (Phase III; double-blind) at
Week 242
aFull analysis set; numbers reflect maximum sample size
1. Blevins TC et al. Diabetes Obes Metab 2015;17:72633.
* reference insulin glargine is Insulin glargine (Lantus)
2. Rosenstock J et al. Diabetes Obes Metab 2015;17:73441
58
 Lillys insulin glargine and reference insulin glargine
demonstrate similar immunogenicity profile in T1DM
and T2DM patients
T1DM1 T2DM2

INSULIN reference INSULIN reference

GLARGINE insulin GLARGINE insulin
P value P value
(BASAGLAR) glargine* (BASAGLAR) glargine*
(n=268a) (n=267a) (n=376a) (n=380a)

Patients with
SAFETY
detectable
107 (40) 105 (39) ns 56 (15) 40 (11) ns
antibodies, n
(%)a

% insulin
antibody
0.92 0.89 ns 1.07 0.65 ns
binding
(median)b

Studies ABEB (Phase III; open-label)1 and ABEC (Phase III; double-blind)
aMeasured for the overall 52-week study period in T1DM and the overall

24-week treatment period in T2DM; bMeasured at Week 52 LOCF (endpoint) in T1DM

and at Week 24 LOCF (endpoint) in T2DM; % insulin antibody binding corresponds to
the level or titer of antibody binding
LOCF, last observation carried forward 1. Blevins TC et al. Diabetes Obes Metab 2015;17:72633.
* reference insulin glargine is Insulin glargine (Lantus) 2. Rosenstock J et al. Diabetes Obes Metab 2015;17:73441

59
 The incidence of allergic events is similar with Lillys
insulin glargine and reference insulin glargine in T1DM
INSULIN reference
GLARGINE insulin
AEs, n (%)a
(BASAGLAR) glargine*
(n=268b) (n=267b)

Special topic assessment of allergic reactions 20 (8) 11 (4)

Pruritus, rash, dermatitis, otherc 7 (3) 4 (2)
Arthralgia, arthritis 4 (2) 5 (2)
Injection site (reaction, induration, nodule, swelling) 6 (2) 2 (1)
Drug hypersensitivity and hypersensitivity 1 (<1) 1 (<1)
Allergic respiratory symptom, asthma 2 (1) 0
Injection site reaction (patient questionnaires) 7 (3) 3 (1)
Pain 6 (2) 2 (1)
Pruritus 2 (1) 1 (<1)
Rash 2 (1) 1 (<1)

Study ABEB (Phase III; open-label) over 52 weeks1;

P>0.05 for all treatment comparisons with the exception of pruritus and rash injection
site reactions; treatment comparisons were not performed if there were <4 patients
with events1
aPatients may be counted in >1 category;
bFull analysis set; numbers reflect maximum sample size;
cPhotosensitivity reaction, urticaria

* reference insulin glargine is Insulin glargine (Lantus) 1. Blevins TC et al. Diabetes Obes Metab 2015;17:72633

60
 The incidence of allergic events is similar with Lillys
insulin glargine and reference insulin glargine in T2DM
reference
INSULIN GLARGINE
insulin
AEs, n (%)a (BASAGLAR)
glargine*
(n=376b) (n=380b)

Special topic assessment of allergic reactions 21 (6) 27 (7)

Pruritus, rash, dermatitis, otherc 8 (2) 12 (3)
Arthralgia, peri-arthritis 7 (2) 9 (2)
Injection site (reaction, pruritis, induration) 5 (1) 4 (1)
Asthma, nasal edema 3 (1) 5 (1)
Injection site reaction (patient questionnaires) 13 (4) 11 (3)
Pain 10 (3) 5 (1)
Pruritus 4 (1) 4 (1)
Rash 3 (1) 3 (1)

Study ABEC (Phase III; double-blind) over 24 weeks1;

P>0.05 for all treatment comparisons with the exception of injection site reactions
where treatment comparisons were not performed1
aPatients may be counted in >1 category;
bFull analysis set; numbers reflect maximum sample size;
cAngioedema, macular rash, papular rash, pruritic rash, vesicular rash

* reference insulin glargine is Insulin glargine (Lantus) 2. Rosenstock J et al. Diabetes Obes Metab 2015;17:73441

61
INSULIN GLARGINE (BASAGLARTM) device
INSULIN GLARGINE (BASAGLARTM KwikPenTM) can be administered conveniently
using the Pre-filled Pen

1. Basaglar SmPC

62
 The overall clinical profile of Lillys insulin
glargine is similar to that of the reference
insulin glargine
INSULIN GLARGINE (BASAGLARTM) is a suitable therapeutic option in patients for
whom insulin glargine is considered an appropriate treatment

INSULIN GLARGINE
reference insulin glargine*
(BASAGLARTM)

Similar efficacy1

OVERALL CLINICAL
Similar safety profile1
PROFILE

Same dosing1

INSULIN GLARGINE (BASAGLARTM) can be taken with mealtime insulin in T1DM

and T2DM patients, and can also be taken in conjunction with OADs in patients
with T2DM1,2

1. EMA. Assessment Report. 2014;

* reference insulin glargine is Insulin glargine (Lantus) 2. . Basaglar SmPC

63
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