1. A study analyzed data from 185 Indian patients with type 2 diabetes who initiated or switched to insulin degludec/insulin aspart (IDegAsp) in a real-world clinical setting. 2. After 36 weeks, patients experienced a mean reduction in HbA1c of 1.6% from a baseline of 9.8%, as well as a mean reduction in fasting plasma glucose of 49 mg/dL from a baseline of 190 mg/dL. 3. The initiation of IDegAsp was associated with significantly lower rates of hypoglycemia compared to prior treatment.

1. Novo Nordisk®
Lessons for judicious use of insulin –
Perspective on timely insulin initiation

2. Financial disclosure
The speaker has been commercially supported by Novo Nordisk for this promotional
meeting, in return for providing a service, and has no actual or potential conflict of
interest in relation to this presentation
*The information, advocacy, suggestions and/or updates provided during the scheduled meeting is not intended or implied to be
directed towards HCPs practicing outside the geographical territory of India

3. By the time diagnosis of diabetes is made, patients
have lost ~80% of their ß-cell function
DeFronzo RA, Eldor R, Abdul-Ghani M. Diabetes Care. 2013 Aug;36 Suppl 2:S127-38

4. Amongst all the therapeutic options for managing T2DM,
Insulin offers maximum glycemic efficacy
Adapted from Lebovitz. 1999;7:139–53 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:1249–58) *Mean derived from clinical studies with dapagliflozin 5 mg and canagliflozin 100 mg; AGI, alpha-glucosidase inhibitor; DPP-4i,
dipeptidyl peptidase-4 inhibitor; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HbA1c, glycated haemoglobin; Met, metformin; SU, sulphonylurea; TZD, thiazolidinedione;1.. Esposito K et al. Diabetes Obes Metab 2012;14:228–233; 2. US FDA
Endocrinologic & Metabolic Advisory Committee: Dapagliflozin background Document. 13 Jun 2011; 3. US FDA Endocrinologic & Metabolic Advisory Committee: Canagliflozin background Document. Jan 2013
-1.12
-0.74 -0.72
-0.96
-0.77
-0.64
-1.21 -1.28
-1.91
-1.08
-1.22
-0.74
-3
-2
-1
0
Change
in
HbA
1c
(%)
GLP-1 RA
(n=5783)1
DPP-4i
(n=13,847)1
AGI
(n=1120)1
TZD
(n=6655)1
SU
(n=5895)1
Glinides
(n=1050)1
Met
(n=4827)1
Basal
(n=21,615)1
Premix
(n=11,921)1
Prandial
(n=2597)1
Basal bolus
(n=2967)1
SGLT-2i
(n=12,090)2,3*

5. Only 31.3% people with diabetes are being managed with insulin
Delayed insulin initiation : Often beyond 10 years
Addition of the 4th OAD offers diminishing benefit
Nair DR et al. Diabetes Metab Syndr . 2020 Sep 14;14(6):1851-1857; Calvert et al. Br J Gen Pract 2007;57:455-460; Singla R et al. Indian J Endocr Metab 2019;23:40-5

6. Achieving glycemic goals by timely treatment optimization
Adapted from : Prato Del S et al. Int J Clin Pract . 2005 Nov;59(11):1345-55.
7
6
9
8
10
HbA1c
(%)
Duration of diabetes
OAD
monotherapy
Diet and
exercise
OAD
combination
OAD
monotherapy
uptitration
OAD+ multiple
daily insulin
injections
OAD+
insulin
Diagnosis +5 years +10 years +15 years
Sequential therapy approach Early combination therapy
HbA1c=7%
HbA1c=6.5%

7. Agenda
02
01 03
100 years of Insulin:
Time to take action
to facilitate Insulin
adoption
Insulin Initiation-
exploring the options
Insulin Initiation in
Indian context:
Making a judicious
choice for optimal
glycemic control

8. Options for Insulin Initiation
OD Basal Insulin + OADs
OD/BD Premix Insulin + OADs
OD IDegAsp + OADs
Chawla R et al. Indian J Endocr Metab 2020;24:1-122

9. High carbohydrate diet is a common Indian reality
Joshi SR et al. BMJ Open 2014;4:e005138
63%
15%
22%
North
Carbohydrate Protein Fat
64%
14%
22%
South
Carbohydrate Protein Fat
65%
16%
19%
East
Carbohydrate Protein Fat
61%
14%
25%
West
Carbohydrate Protein Fat
67%
14%
19%
Central
Carbohydrate Protein Fat
61-70% energy intake in Indians is through carbohydrates present in the diet

10. In a subject who eats 3 times a day, 50% of the day is
spent in post-prandial phase
Monnier L. European Journal of Clinical Investigation. 2000;30(2):3-11
Treatment strategies should address both meal-related & fasting
hyperglycemia for optimum HbA1c control
Indian scenario is worse
owing to high
carbohydrate diet

11. High PPG and high FPG contributes to high HbA1c
Consequence of delayed insulin initiation
172
194 194 192
253
289 285 279
0
50
100
150
200
250
300
iDCI®* A1chieve PRESENT IMPROVE
Glucose
level
(mg/dl)
FPG PPG
FPG
HbA1c
PPG
8.56 9.2 9.23 9.23
* National level aggregated iDCI® data on file (Jul-Sep 2020); Das AK et al. J Diabetol 2021;12:239-45; Mohan V et al. JAPI (Suppl) 201361:12–15.; Srishyla MV, Yap C on behalf of PRESENT-INDIA Study Group
Presented at IDF - 19th World Diabetes Congress; Valensi et al. Int J Clin Pract 2008;62:1809–19; International Diabetes Federation. IDF diabetes atlas - 9th edition 2019
HbA1c

12. Unlike western population, PPG should be controlled at
all levels of HbA1c in Asians
Wang JS et al. Diabetes Metab Res Rev. 2011; 27: 79–84
Significant
contribution from
PPG even at higher
HbA1c levels in
Asians unlike the
Caucasian data from
Monnier et al.
Higher
contribution of
PPG at lower
HbA1c levels
similar to
Caucasian data
from Monnier
et al.
The Asian picture

13. Status of glycemic control in Indian patient demands
TOTAL control
Patient-centric advances: Combination insulins
RHI: Regular Human Insulin; NPH: Neutral protamine Hagedorn; IAsp: Insulin aspart; pIAsp: Protaminated aspart; IDeg: Insulin degludec
Mohan V et al. J Assoc Physicians India . 2017 Apr;65(4):59-73

14. Agenda
01
100 years of Insulin:
Time to take action
to facilitate Insulin
adoption
02 03
Insulin Initiation-
exploring the options
Insulin Initiation in
Indian context:
Making a judicious
choice for optimal
glycemic control

15. Novo Nordisk®
IDegAsp: A 2-in-1 solution suited to Indian realities of
diabetes management
Kumar A et al. J Diabetol 2020;11:148-57; Havelund et al. Pharm Res. 2015;32:2250–8
It’s a basal insulin with a built-in rapid-acting component for a reason
The pharmacological properties make IDegAsp a prudent choice for
OD initiation and subsequent intensification

16. IDegAsp phase 3 clinical trial programme
Overview
Mehta R et al. Diabetes Obes Metab. 2020;22:1961–1975.

17. Indications for using IDegAsp
Ryzodeg CDSCO approved package insert version (8-9564-26-010-7), dated (11 JAN 2019)
Patients uncontrolled on OADs
Patients uncontrolled on
basal insulin
Patients uncontrolled on
premix insulins
Patients uncontrolled on
basal+bolus therapy
‘Start and Stay therapy’
T1DM or T2DM, >18 years
Elderly with T2DM
T2DM with
renal/ hepatic impairment
T2DM with other co-morbidities
Patient type

18. Fulcher G, Akhtar S, Al-Jaser S, et al. Improved glycaemic control in people with type 2 diabetes initiating or switching to IDegAsp from any anti-hyperglycaemjc treatment in a real-world setting across six countries.
Abstract and oral presentation at Australasian Diabetes Congress, August 13, 2021.
• Non-interventional
• Multicentre
• Prospective, primary data collection
• Visit frequency according to the local
standard of care
• Physician’s decision to start
treatment with IDegAsp
• Age ≥18 years
• Diagnosed with T2D and treated
with any anti-hyperglycaemic
treatment other than IDegAsp
• Available HbA1c value ≤12 weeks
Study information Key inclusion criteria
Adults with T2D
N=1112
IDegAsp as per local practice
Week 0 (Visit 1)
• Informed consent
• Treatment Start
Observation period (Visit 2.x) Weeks 26–36 (Visit 3)
• End of study
Malaysia India Saudi Arabia Philippines Australia South Africa
Study Design

19. * Significant reduction
Fulcher G, Akhtar S, Al-Jaser S, et al. Improved glycaemic control in people with type 2 diabetes initiating or switching to IDegAsp from any anti-hyperglycemjc treatment in a real-world setting across six countries.
Abstract and oral presentation at Australasian Diabetes Congress, August 13, 2021.
Results
In the ARISE study, initiation with or switch to
IDegAsp in the global cohort, led to:
HbA1c
1.4% *
FPG
49 mg/dl *
Hypoglycemia
Significantly lower
risk of hypoglycemic
events
Resource utilization
Significant reduction in
• Outpatient visits - 61% *
• Self reported
workdays missed - 90% *

20. Baseline characteristics
Indian cohort
Overall
N=185
Age (years), mean (SD) 58.1 (10.3)
Sex, n (%)
Female 79 (42.7)
Male 106 (57.3)
Body weight (kg), mean (SD) 70.8 (11.5)
Duration of diabetes (years), mean (SD) 14.4 (8.1)
BMI (kg/m2), mean (SD) 26.5 (3.9)
FPG (mg/dl), mean (SD) 190.0 (65.8)
HbA1C(%), mean (SD) 9.8 (1.8)
Baruah MP et al. Glycemic change in adults with type 2 diabetes initiating or switching to insulin degludec/insulin aspart (IDegAsp) in real-world-setting: An analysis of Indian cohort of ARISE study
Abstract and poster presentation at ESICON 2021, December 10-11, 2021

21. Reasons for starting IDegAsp treatment
To improve the patient's glycemic control
Fewer injections than basal and bolus therapy
Flexibility in the dosing regimen
To lower the risk of hypoglycemia
No reconstitution needed
Indian cohort n = 185
Improved glycemic control, lower risk of hypoglycemia, advantage of flexibility and need for fewer
injections were the common reasons for starting IDegAsp
40
48
50
54
182
Baruah MP et al. Glycemic change in adults with type 2 diabetes initiating or switching to insulin degludec/insulin aspart (IDegAsp) in real-world-setting: An analysis of Indian cohort of ARISE study
Abstract and poster presentation at ESICON 2021, December 10-11, 2021

22. Frequency prescribed by physician
Once daily Twice daily
104 (56.2%)
81 (43.8%)
Baruah MP et al. Glycemic change in adults with type 2 diabetes initiating or switching to insulin degludec/insulin aspart (IDegAsp) in real-world-setting: An analysis of Indian cohort of ARISE study
Abstract and poster presentation at ESICON 2021, December 10-11, 2021

23. Change in HbA1c from baseline
Data are change from baseline to Week 36 [95% CI], *P<0.0001
Mean at baseline = 9.7%
Mean at EOS = 8.3%
Mean change = -1.4% [-1.51; -1.29]*
Mean at baseline = 9.8%
Mean at EOS = 8.2%
Mean change = -1.6% [-1.83; -1.42]*
N = 1102 N = 185
Fulcher G, Akhtar S, Al-Jaser S, et al. Improved glycaemic control in people with type 2 diabetes initiating or switching to IDegAsp from any anti-hyperglycaemjc treatment in a real-world setting across six countries.
Abstract and oral presentation at Australasian Diabetes Congress, August 13, 2021.
Baruah MP et al. Glycemic change in adults with type 2 diabetes initiating or switching to insulin degludec/insulin aspart (IDegAsp) in real-world-setting: An analysis of Indian cohort of ARISE study
Abstract and poster presentation at ESICON 2021, December 10-11, 2021

24. ARISE: Change in HbA1c from baseline
By prior treatment subgroup
Baruah MP et al. Glycemic change in adults with type 2 diabetes initiating or switching to insulin degludec/insulin aspart (IDegAsp) in real-world-setting: An analysis of Indian cohort of ARISE study
Abstract and poster presentation at ESICON 2021, December 10-11, 2021
-1.9 (1.42)
-2.1 (1.81)
-1.7 (2.30)
-1.0 (2.40)
-0.9 (2.51)
-2.5
-2.0
-1.5
-1.0
-0.5
0.0
Mean
change
in
HbA
1c
from
baseline
(%)
OADs only
9.8
Basal only
10.1
GLP-1 RA
9.1
Basal + bolus
9.5
Premix
9.7
Baseline (%):

25. Change in FPG (mg/dL) from baseline
*P-value <0.0001
Mean at EOS = 141.9 mg/dL
Mean change
-52.2 mg/dL [-60.65; -43.66]*
Baseline
190.0
mg/dL
Mean at EOS = 147.1 mg/dL
Mean change
-49 mg/dL [-53.77; -44.29]*
Baseline
196.1
mg/dL
Fulcher G, Akhtar S, Al-Jaser S, et al. Improved glycaemic control in people with type 2 diabetes initiating or switching to IDegAsp from any anti-hyperglycaemjc treatment in a real-world setting across six countries.
Abstract and oral presentation at Australasian Diabetes Congress, August 13, 2021.
Baruah MP et al. Glycemic change in adults with type 2 diabetes initiating or switching to insulin degludec/insulin aspart (IDegAsp) in real-world-setting: An analysis of Indian cohort of ARISE study
Abstract and poster presentation at ESICON 2021, December 10-11, 2021

26. Number of participants experiencing
≥1 hypoglycemic episode
128
27
44
4
0
20
40
60
80
100
120
140
Within 4 weeks prior to initiation of
IDegAsp
Within 4 weeks prior to end of study
Non severe hypoglycemia episodes
23
2
3
1
0
5
10
15
20
25
Severe hypoglycemia episodes
Fulcher G, S, Al-Jaser S, Akhtar, et al. IDegAsp treatment was associated with improved glycemic control and reduced hypoglycemia rates versus previous therapy regimens: a real-world study. Presented at the International Diabetes Federation (IDF) virtual congress, 6–11 December 2021.
Baruah MP et al. Glycemic change in adults with type 2 diabetes initiating or switching to insulin degludec/insulin aspart (IDegAsp) in real-world-setting: An analysis of Indian cohort of ARISE study Abstract and poster presentation at ESICON 2021, December 10-11, 2021
*
* p=0.0004, # p<0.0001
#

27. Number of hypoglycemic episodes
364
47
162
8
0
50
100
150
200
250
300
350
400
51
4
3
1
0
10
20
30
40
50
60
Non severe hypoglycemia episodes Severe hypoglycemia episodes
* p=0.0004, # p<0.0001
*
#
Fulcher G, S, Al-Jaser S, Akhtar, et al. IDegAsp treatment was associated with improved glycemic control and reduced hypoglycemia rates versus previous therapy regimens: a real-world study. Presented at the International Diabetes Federation (IDF) virtual congress, 6–11 December 2021.
Baruah MP et al. Glycemic change in adults with type 2 diabetes initiating or switching to insulin degludec/insulin aspart (IDegAsp) in real-world-setting: An analysis of Indian cohort of ARISE study Abstract and poster presentation at ESICON 2021, December 10-11, 2021

28. Resource utilization associated with
diabetes and its complications
1012
72
242
2
498
32 28 0
0
200
400
600
800
1000
1200
Number
of
events
Observed within 12 weeks prior initiation of
IDegAsp
Observed within 12 weeks prior to end of study
or at discontinuation
Self-reported outpatient visits Self-reported workdays missed
R=0.39 [0.31; 0.49]
P<0.0001
R=0.10 [0.04; 0.22]
P<0.0001
61%
90%
Fulcher G, S, Al-Jaser S, Akhtar, et al. IDegAsp treatment was associated with improved glycemic control and reduced hypoglycemia rates versus previous therapy regimens: a real-world study. Presented at the International Diabetes Federation (IDF) virtual congress, 6–11 December 2021.
Baruah MP et al. Glycemic change in adults with type 2 diabetes initiating or switching to insulin degludec/insulin aspart (IDegAsp) in real-world-setting: An analysis of Indian cohort of ARISE study Abstract and poster presentation at ESICON 2021, December 10-11, 2021

29. Conclusion: ARISE study
India cohort
In ARISE, initiation or switch to IDegAsp led to
* Numerically lower; † Numerically lower for self-reported outpatient visits & workdays missed
Significant decrease in HbA1c
Significant decrease in FPG
Lower hypoglycemic events*
Lower resource utilization†
Baruah MP et al. Glycemic change in adults with type 2 diabetes initiating or switching to insulin degludec/insulin aspart (IDegAsp) in real-world-setting: An analysis of Indian cohort of ARISE study
Abstract and poster presentation at ESICON 2021, December 10-11, 2021

30. RSSDI-ESI Clinical Practice Recommendations 2020
Initiate, optimize
and intensify with a
single device
Avoid using insulin as a threat
Alleviate patient anxiety about insulins
Insulin therapy should be considered in all patients
failing to achieve glycemic targets on 3 oral agents
Chawla R et al. Indian J Endocr Metab 2020;24:1-122 RyzodegTM CDSCO approved package insert version, dated (14 OCT 2021)
OD BID
IDegAsp is recommended
as a choice for insulin initiation

31. Summary
• There is a discordance between innovation and adoption of
insulin even though Insulin offers maximum glycemic
efficacy. This demands facilitation of timely insulin initiation
• High carb diet resulting in high PPG levels is a common
Indian reality
• IDegAsp is a recommended choice for insulin initiation in
Indian people with T2DM as it offers TOTAL (PPG+FPG)
control
#1
#2
#3