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1. *Pediatrik ≥2 tahun, DMT 1 dewasa, DMT 2 dewasa, ibu hamil, pasien rumah
sakit, geriatri, gangguan ginjal/hepar, pompa insulin
(1) NovoRapid®. Indonesia Prescribing Information, 2018. (2) IMS Health
Database, Jan 2016. (3) Literature search, March 2015. (4) Pfutzner et al, 2008.
(5) Pfutzner et al, 2009
Familiar dengan NovoRapid®
?
 NovoRapid® telah disetujui untuk digunakan
pada berbagai populasi pasien dengan
cakupan indikasi luas*1.
 NovoRapid® adalah insulin prandial
terpercaya yang menawarkan kontrol gula
darah sesudah makan, dengan lebih dari
4,5 juta pasien di seluruh dunia 2.
 Keamanan NovoRapid® terbukti selama
lebih dari 20 tahun, dan telah dipelajari
pada lebih dari 24.000 pasien di dunia**3.
 Mudah digunakan, perangkat dengan kode
berwarna yang dirancang untuk kenyamanan
pasien 1,4,5.

2. Simplifying insulin therapy with Co-
Formulation Insulin
RYZODEG®
For Healthcare Professional Only
2020© NovoNordisk A/S

3. Disclosure
I have received honorarium as speaker/consultant, support for research/attendance at
educational meetings from:
• List names of companies

4. Insulin optimisation and intensification should follow
disease progression
Beta-cell
function
(%)
Treatment optimisation and intensification
Lifestyle + OADs
Basal and 1–4 bolus or premix
Basal insulin + OADs
Schematic diagram adapted from Kahn. Diabetologia 2003;46:3–19
Inzucchi et al. Diabetologia 2012;55(6):1577–96
Titrate dose to reach/maintain glycaemic targets
Intensify for mealtime insulin coverage
Initiate
Optimise
Intensify

5. Glycemic control matters but basal insulin
intensification is often delayed
Intensification of basal
insulin is often delayed
Change in insulin regimen over 3 years in UK*
60% 19% 14%
No switch/
intensification
Intensified
(prandial/premix)
Switched
(premix)
HbA1c at change 8.4% 9.2/9.3% 9.5%
Year 3 HbA1c 8.1% 8.6/8.7% 8.5%
*7% discontinued; N/A, not applicable
Blak et al. Diabet Med. 2012;29:e13–20; 4):6–10

6. Insulin therapy from basal to basal-bolus is complex1
BID, twice daily; OAD, oral antidiabetic drug; OD, once daily; IAsp, insulin aspart; TID, thrice daily
1. Adapted from American Diabetes Association. Diabetes Care 2017;40(Suppl.1):S64–S74 | 2. Peyrot et al. Diabet Med. 2012;29: 682–9
3. Jarab et al. Int J Clin Pharm. 2014;36(4):725-33
57% of insulin
patients reported
intentional insulin
omission
20% reported
skipping injections
“sometimes” or
“often”
Additional bolus insulin (2-4) pens/injections/day:
• Need more education, monitoring
• Lead to complexity & lower adherence2,3

7. Fear of hypoglycaemia conflicts with treatment success for both
patients and clinicians
*, Total patient sample, n=335 (T1D, n=202; T2D, n=133); #, GAPP™ (A global internet survey of patient and physician beliefs
regarding insulin therapy): total patient sample, n=1250 physicians. T1D, type 1 diabetes; T2D, type 2 diabetes
1. Leiter et al. Can J Diabetes 2005;29:186–92. 2. Peyrot et al. Diabet Med 2012;29:682–9
74%
79%
43%
58%
0%
20%
40%
60%
80%
100%
Non-severe episodes Severe episodes
Patients
modifying
insulin
dose
T1D
T2D
72%
79%
0 20 40 60 80 100
Percentage
I would treat my patients more aggressively if
there was no concern about hypoglycaemia#,2
Percentage of patients decreasing their insulin
dose following a hypoglycaemic event*,1
Primary care physicians
Diabetes specialists

8. Summary of Key Challenges for T2DM patient needing
insulin treatment
More than 60%
of T2DM on basal
insulin are often
delay to
intensified1
57%
of patients with
diabetes report
skipping their insulin
injections2,3
58% Patients reduce
insulin doses
in response to
experiencing
hypoglycaemia4
1. Blak et al. Diabet Med. 2012;29:e13–20; 4):6–10 2.Peyrot et al. Diabet Med. 2012;29: 682–9
3. Jarab et al. Int J Clin Pharm. 2014;36(4):725-33 4. Leiter et al. Can J Diabetes 2005;29:186–92.

9. Development of a basal & bolus Co-Formulation
in one SINGLE injection
Control Overall glycaemic
control (HbA1c, FPG & PPG)
Mimicking insulin endogenous
response
Adapted to patient’s convenience
with Once daily or split dose
administration
Reduce COMPLEXITY of Insulin
treatment
Desired clinical benefits Desired action profile
of co-formulation
 Ultra-long duration of action for
basal component (half-life >24
hours)
 Flat profile for the basal
component & Rapid-acting for
bolus component
 Possibility of Flexible Dosing
 Good efficacy & safety profile

10. First in class Co-formulation Insulin
[basal insulin with an ultra-long duration of action and a mealtime insulin in one
pen1]
. Kalra S, Diabetes Ther. 2014 Jun;5(1):65-72.

11. Conceptual: Co-Formulation Insulin will address our
problem on
References: 1. Haahr H et al. Clin Pharmacokinet 2017;56(4):339–354 2. Heise et al. Diabetes Obes Metab 2012;14:859-64 3. Sajay Karla.
Diabetes Ther (2014) 5:65-72
Glycaemic Control
Providing basal and prandial
coverage in one injection1
Simplifying Insulin Therapy
Associated with simple regimen
and fewer injection3
Assurance of
Hypoglycaemia
Co-formulation Insulin contain
Insulin Degludec with flat and
low variability profile2

12. PowerPoint Presentation Date 12
STEP BY STEP TRIAL

13. 532 subjects
• Basal insulin ≥90 days +/- OAD
• HbA1c 7.0-10.0%
Trial information
• Open label
• Parallel
• Multinational
• Treat-to-target
Primary endpoint
• Change from baseline in HbA1c
after 26 weeks
Randomisation
(1:1)
0 26 38
Ryzodeg® Step-by-Step trial – Study design1
A 38 week trial comparing the efficacy and safety profile parameters of insulin degludec/insulin aspart (Ryzodeg®) vs.
insulin glargine U100 plus insulin aspart in subjects with type 2 diabetes treated with basal insulin with or without oral
antidiabetic treatment, in need of treatment intensification
OD: Once daily, BID: ‘Bis in die’ (twice daily), OAD: Oral anti-diabetic drug, BG: Blood glucose
Ryzodeg® OD
± OADs
Glargine U100 OD
+ IAsp OD
± OADs
Ryzodeg®
OD/BID
± OADs
Glargine U100 OD +
IAsp OD/BID/TID
± OADs
0-26 weeks
0-38 weeks
1. Philis-Tsimikas A, Astamirova K, Gupta Y, et al. Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the
IDegAsp co-formulation with insulin glargine U100 and insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. Diabetes Res
and Clin Pract. 2019;147:157-165.

14. IDegAsp: Similar HbA1c reduction vs Basal Plus with fewer
injections and significantly lower total insulin dose
Non-inferiority confirmed with respect to pre-specified limit of 0.4%
1.1%
HbA1c
Reduction
26 weeks
Estimated treatment difference:
0.07%
[95% CI:–0.06; 0.21]
P=NS
0
0.0
5.6
6.0
6.4
7.6
8.0
8.4
8.8
6.8
7.2
9.2
2 4 6 8 10 12 14 16 18 22 24 26
20
Mean
HbA
1c
(%)
Time (weeks)
INJECTIONS
PER DAY
2
INJECTION
PER DAY
1
Ryzodeg® OD (n=267)
Glargine U100 OD + IAsp OD (n=265)
Data adapted from the 38-week trial
Ryzodeg® OD was non-inferior to glargine U100 + IAsp in HbA1c reduction from baseline to end of 26 weeks
1. Philis-Tsimikas A, Astamirova K, Gupta Y, et al. Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100 and
insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. Diabetes Res and Clin Pract. 2019;147:157-165.

15. Non-inferiority confirmed with respect to pre-specified limit of 0.4%
1.3%
HbA1c
Reduction
38 weeks
*Rounded to the nearest integer. 1.62 and 2.85 mean injections per day at 38 weeks with Ryzodeg® OD/BID and glargine U100 OD + 1-3 IAsp respectively
0
0.0
5.6
6.0
6.4
7.6
8.0
8.4
8.8
6.8
7.2
9.2
2 4 6 8 10 12 14 16 18 22 24 26
20 38
36
34
32
30
28
Mean
HbA
1c
(%)
Time (weeks)
INJECTIONS
PER DAY*
3
INJECTIONS
PER DAY*
2
Ryzodeg® OD/BID (n=267)
Glargine U100 OD + IAsp
1-3 times per day (n=265)
Estimated treatment difference: 0.09%
[95% CI:–0.04; 0.22]
P=NS
Ryzodeg® OD was non-inferior to glargine U100 + 1-3 IAsp in HbA1c reduction from baseline to end of 38 weeks
1. Philis-Tsimikas A, Astamirova K, Gupta Y, et al. Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100
and insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. Diabetes Res and Clin Pract. 2019;147:157-165.
IDegAsp: Similar HbA1c reduction vs Basal Bolus with
fewer injections and significantly lower total insulin dose
INJECTIONS
PER DAY
2
INJECTION
PER DAY
1

16. IDegAsp: Lower rates of nocturnal hypoglycaemia
39%
Reduction
38 weeks
Overall hypoglycaemia refers to severe episodes (requiring assistance from another person), or confirmed hypoglycaemic episodes with a plasma glucose value of <3.1 mmol/L
(56 mg/dL) with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes with an onset between 00:01 and 05:59 hours (both inclusive) were classified as nocturnal
Rate ratio: 0.61 [95% CI: 0.40; 0.93]
P<0.05
Nocturnal hypoglycaemia
☾
Ryzodeg® OD/BID (n=265)
Glargine U100 OD + IAsp
1-3 times per day (n=263)
Nocturnal
confirmed
hypoglycaemia
(cumulative
events
per
patient)
Time (weeks)
0.00
0.08
0.16
0.24
0.56
0.64
0.72
0.80
0.32
0.40
0.48
0.88
0 2 4 6 8 10 12 14 16 18 22 24 26
20 38
36
34
32
30
28
Nocturnal hypoglycaemia: IDegAsp OD/BID vs glargine U100 OD
+ 1-3 IAsp
1. Philis-Tsimikas A, Astamirova K, Gupta Y, et al. Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the
IDegAsp co-formulation with insulin glargine U100 and insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. Diabetes Res
and Clin Pract. 2019;147:157-165.

17. Fewer injections vs glargine U100 + IAsp
Two insulins in one pen meant fewer injections with one pen at 26 weeks vs glargine U100 OD + IAsp OD
Step-by-Step Results – Number of injections1
26 weeks
1 injection/day
Ryzodeg® once-daily
2 injections/day
Basal-plus
vs.
1. Philis-Tsimikas A, Astamirova K, Gupta Y, et al. Similar glycaemic control with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100 and
insulin aspart in basal insulin-treated subjects with type 2 diabetes mellitus. Diabetes Res and Clin Pract. 2019;147:157-165.
38 weeks
2 injections/day*
Ryzodeg®
3-4 injections/day*
Basal and bolus
vs.

18. Numerically lower risk of hypoglycaemia
vs glargine U1005
Fewer injections with Ryzodeg® than
glargine U100 + IAsp5
Successful reductions in HbA1c with once
daily dosing5
StepbyStep - Summary
More than 60%
of T2DM on basal insulin
are often delay to
intensified1
Patients reduce insulin
doses
and skip injections in
response to experiencing
Hypoglycaemia2,3
57%
of patients with diabetes
report skipping their
insulin injections4
1. Blak et al. Diabet Med. 2012;29:e13–20; 4):6–10 2.Peyrot et al. Diabet Med. 2012;29: 682–9
3. Jarab et al. Int J Clin Pharm. 2014;36(4):725-33 4. Leiter et al. Can J Diabetes 2005;29:186–92. 5. Philis-Tsimikas A, Astamirova K, Gupta Y, et al. Similar glycaemic control
with less nocturnal hypoglycaemia in a 38-week trial comparing the IDegAsp co-formulation with insulin glargine U100 and insulin aspart in basal insulin-treated subjects with type
2 diabetes mellitus. Diabetes Res and Clin Pract. 2019;147:157-165.

19. Clinical Use of IDegAsp

20. *do not store above 30’C
IDegAsp, insulin degludec/insulin aspart
Ryzodeg®. Indonesia Prescribing Information. 2020
Device: IDegAsp is delivered in the FlexTouch® pen
Maximum dose/injection:
80 U
Injection sites:
Rotate frequently within the chosen area (abdominal
wall, the upper arm or the thigh)
Storage:
Opened pens: 2–8°C or room temperature* for 4 weeks
Unopened pens: 2–8°C (do not freeze) until expiry date
Needle:
Do not re-use needles
70/30
–
3
ml
prefilled
pen

21. INITIATION SWITCHING
BB, basal–bolus; BID, twice daily; IDegAsp, insulin degludec/insulin aspart; Ind. req., individual requirements; OAD, oral antidiabetic drug; OD, once daily; T2D, type 2 diabetes;
U, units
Ryzodeg® Indonesia Prescribing Information 2020. Mehta R, et al. Diabetes Obes Metab. 2020;1–15.
• Administer OD with the largest
meal……..
• Administer:
– alone or
– in combination with OADs or bolus
insulin
• Recommended (total) daily starting
dose 10 U
• Requires subsequent individual dosage
adjustments Recommend using CGM during the
transfer and in the following weeks
OD
1:1
OD
Basal/Premix IDegAsp
BID
1:1
≥BID
Basal/Premix IDegAsp
IDegAsp
generally initiated on the same number BASAL unit
BB
Dosing of IDegAsp in T2D

22. • Dose adjustments based on
lowest of the 3 preceding FPG
measurements
• FPG target should be
individualised
• Do not increase dose if
hypoglycaemia or symptoms
suggestive of hypoglycaemia are
present
• For twice-daily dosing, consider
adjusting one dose at a time
during weekly titration
FPG, fasting plasma glucose; IDegAsp, insulin degludec/insulin aspart; T2D, type 2 diabetes
1. Fulcher et al. Diabetes Care 2014;37:2084–90; 2. Gerety et al. Endocr Pract 2016;22:546–54; 3. Endocrinologic and Metabolic Drug Advisory Committee. Insulin degludec and insulin
degludec/insulin aspart treatment to improve glycemic control in patients with diabetes mellitus: NDAs 203314 and 203313 briefing document. Published November 8, 2012
Suggested once-weekly titration schedule for
IDegAsp in T2D
At
individualised
target
Below target
Above target
Below target
At
individualised target
Above target +2
units
Maintain
dose
-2
units

23. Use of IDegAsp in special populations
Can be used in adolescents
and children ≥ 2
years of age.
Pediatrics (approved)
Can be used in renal and
hepatic impaired patients.
Renal and Hepatic impairement
Glucose monitoring should be
intensified and doses should
be individualized.
Can be used in the elderly.
Glucose monitoring should be
intensified and doses should
be individualized.
Elderly (>65 years old)
There is no clinical experience
with use of IDegAsp in
pregnant women.
Pregnancy
Indonesia Prescribing Information 2018.

24. Summary
• More than 60% of type 2 diabetes patients on basal insulin are often delayed to
intensified
• Due to complex regimen: 57% of patients with diabetes report skipping their
insulin injections2
• There is a need of innovation to tackle this problem with development of First in
class co-formulation Insulin
• Based on Philis-Tsimikas study, Ryzodeg® shown:
• Similar HbA1C reduction vs Basal plus and basal bolus3
• Significantly lower risk of of Nocturnal Hypoglycemia
• Less Injection vs Basal Plus and Basal Bolus
1. Blak et al. Diabet Med. 2012;29:e13–20; 4):6–10 2. . Peyrot et al. Diabet Med. 2012;29: 682–9 3. . Philis-Tsimikas A, et al
Diabetes Res and Clin Pract. 2019;147:157-165.