How to Manage T2DM in Elderly & CKD

Patients with Co-Formulation Insulin

dr. R. Bowo Pramono, Sp.PD-KEMD, FINASIM

Disclosure

I have received honorarium as speaker/consultant, support for research/attendance at

educational meetings from :
• Novo Nordisk
IDegAsp- First Coformulation Insulin
IDegAsp®: First in Class Co-Formulation Insulin1,5

2,3

1. Indonesia Ryzodeg® Prescribing Information 2022. 2. Heise T, et al. Diabetes Care. 2011; 34(3): 669-74. 3. Jonassen I, et al. Pharm Res.
2012; 29(8): 2104-14. 4. Heller S, et al. Diabetes Metab Res Rev. 2012; 28: 50-61. 5. Kalra et al. Adv Ther (2018) 35:928-936
Type 2 diabetes and Chronic Kidney Disease
 Clinical use

Use of IDegAsp in special populations or situation1-3

Type 1 Diabetes Hepatic or Renal Impairment

in adults with T1D: (IDegAsp OD + Iasp) vs (Idet OD + Iasp IDegAsp can be used in renal or hepatic impaired
basal bolus) shown non-inferior and relatively lower patients with intensive glucose monitoring and
nocturnal hypoglycaemia risk.
the usual dose adjustment on an individual basis
In children: approved in children ≥ 2 years old

Elderly patients Hospitalised patients

Elderly may consider a good target for treatment with - IDegAsp is not considered suitable for situation in
IDegAsp: which rapid inpatient glycaemic control is desired.
- Regimen is simple & flexible
- PK of IDegAsp not affected by age - Not the preferred choice for steroid-induced
- Shown efficacious & no need special safety precautions hyperglycaemia

Patients on very low calorie Pregnancy

Variability in diet pattern, lifestyle (low carbo, ketogenic There is no clinical experience with the use of
diet), religious practice (fasting month) can influence IDegAsp in pregnant woman3
glycaemic control.
IDegAsp may be useful due to flexibility in dosing schedule

References: 1. Sarah Galtras et al. J Clin Med 2020. 2. Roopa M et al. Diabetes Obes Metab. 2020;1-15 3. Ryzodeg®. Indonesia Prescribing Information 2021.
 CKD is a common complication of T2D, with significant
disease burden
Growing global incidence of diabetes in
CKD is common in diabetes2
adults aged 20–79 years1

2045
2021 T1D

536.6 46%
783.2
MILLION increase MILLION T2D

CKD No CKD

CKD, chronic kidney disease; T1D, type 1 diabetes; T2D, type 2 diabetes
1. Sun H et al. International Diabetes Federation. IDF Diabetes Atlas. Diabetes Research and Clinical Practice. 2022; 183:109119 Available at IDF Diabetes Atlas: Global, regional
and country-level diabetes prevalence estimates for 2021 and projections for 2045 – ScienceDirect; 2. Alicic RZ et al. Clin J Am SoNc ephrol 2017;12:2032-2045
 Screening & Diagnosed CKD
1 Who to screen and when?
T1D
What to do following a positive result?
3
Repeat and confirm:
• If possible, evaluate temporary and for different causes
• Consider the use of cystatin C and creatinine analyses
to estimate GFR more accurately
• Only presence of persistent abnormalities confirm CKD
T2D diagnosis

Yearly starting 5 years Yearly starting at diagnosis Initiate evidence-based treatment

post-diagnosis

2 4
How to screen? What defines CKD diagnosis?*

and/or and/or
+ Persistent† Persistent† Other evidence
UACR eGFR <60 of kidney
Spot UACR eGFR ≥30 mg/g mL/min/1.73 m2 damage

ADA, American Diabetes Association; CGM, continuous glucose monitoring; CKD, cardiovascular disease; KDIGO, Kidney Disease: Improving Global
Outcomes; SMBG, self-monitored blood glucose. American Diabetes Association. Diabetes Care 2022;45(Suppl 1):S1–264.
 Individualized HbA1c targets
• HbA1c range: <6.5% to <8.0% for people with T2D and CKD
1
• These targets are linked with beneficial effects on survival, CV outcomes,
microvascular endpoints, and CKD progression

• Initial HbA1c target of <7.0% in most non-pregnant adult people with T1D and
2
T2D without hypoglycaemia risk
• Reduction of microvascular complications
• Higher HbA1c targets (<8.0%) are recommended for people with limited life
expectancy and when potential risks might impact quality of life

CKD, chronic kidney disease; CV, cardiovascular.

1. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. Kidney Int 2022;102(4S):S1–123; 2. American Diabetes Association.
Diabetes Care 2022;45(Suppl 1):S1–264.
Use of IDegAsp on patients with CKD
Insulin Degludec represent a useful insulin treatment options in subject
with co-morbid diabetes & impaired renal functions

PK properties of insulin degludec are not significantly influenced by renal & hepatic function &
thus specific dose adjustment may not be required for subject with renal & hepatic impairment

Hepatic function
10000

8000 Normal

IDeg concentration
Child-Pugh A
6000 Child-Pugh B

(pmol/L)
Child-Pugh C
4000

2000

0
0 4 8 12 16 20 24

Time since injection (hours)

PK, pharmacokinetic.
Kupčová et al. Clin Drug Investig 2014;34:127–33; Kiss et al. Clin Pharmacokinet 2014;53:175–83; Korsatko et al. Drugs Aging 2014;31:47–53
Use of IDegAsp in renal insufficiency
Label recommendations

India EU US
label label label

Indonesia Label recommendations:

IDegAsp can be used in renal impaired patients. Glucose monitoring is to be
intensified and the insulin dose adjusted on an individual basis
RyzodegTM CDSCO approved package insert version (8-9564-26-010-7), dated (11 JAN 2019); Ryzodeg® August 2018. https://www.novo-
pi.com/ryzodeg7030.pdf EU SmPC, October 2018. Ryzodeg PI Indonesia, 2022
 Kaneko study report
Case report

Hemodialysis case:

61 years old male

patients with T2DM

Insulin Degludec
switched to IDegAsp

This result based on two hemodialysis patients case study reported by Kaneko et.al 2017. Please refer to local product information for information
related to the use of IDegAsp in patient with renal impairment. Kaneko, Shizuka et al. “IDegAsp provides simple intensification without the addition of another
insulin injection and simple delivery system.” Diabetes management 7 (2017): 177.
 Kaneko study
report
Case report

Hemodialysis case:

74 years old male

patients with T2DM &
liver chirossis child A

Regular insulin switched

to IDegAsp
This result based on two hemodialysis patients case study reported by Kaneko et.al 2017. Please refer to local product information for information
related to the use of IDegAsp in patient with renal impairment. Kaneko, Shizuka et al. “IDegAsp provides simple intensification without the addition of another
insulin injection and simple delivery system.” Diabetes management 7 (2017): 177.
 Insulin use in T2DM patients with renal impairment
Insulin Degludec is a useful options for patients with renal impairment, including patients undergoing dialysis.

1 2 3
IDeg is conjugated with fatty Interstitial fluids volume did The pH of the body fluid will
acid & binds to albumin not affect dissolution of change before (PH 7.0) and
IDeg/IDegAsp after hemodialysis (PH 7.4)
Fluctuations of IDeg
concentration remain stable No need IDegAsp dosage IDegAsp did not affected by pH
and minimal adjustment in the day of changes, this will not make a
dialysis. If needed, only minimal. difference in the solubility and
absorption

This result based on two hemodialysis patients case study reported by Kaneko et.al 2017. Please refer to local product information for information
related to the use of IDegAsp in patient with renal impairment. Kaneko, Shizuka et al. “IDegAsp provides simple intensification without the addition of another
insulin injection and simple delivery system.” Diabetes management 7 (2017): 177.

Use of IDegAsp in special populations or situation1-3
Type 1 Diabetes
in adults with T1D: (IDegAsp OD + Iasp) vs (Idet OD + Iasp
basal bolus) shown non-inferior and relatively lower
nocturnal hypoglycaemia risk.
In children: approved in children ≥ 2 years old
Elderly patients
Elderly may consider a good target for treatment with
IDegAsp:
- Regimen is simple & flexible
- PK of IDegAsp not affected by age
- Shown efficacious & no need special safety precautions
Patients on very low calorie
Variability in diet pattern, lifestyle (low carbo, ketogenic
diet), religious practice (fasting month) can influence
glycaemic control.
IDegAsp may be useful due to flexibility in dosing schedule
References: 1. Sarah Galtras et al. J Clin Med 2020. 2. Roopa M et al. Diabetes Obes Metab. 2020;1-15 3. Ryzodeg®.
Indonesia Prescribing Information 2021.
Clinical use
Hepatic or Renal Impairment
IDegAsp can be used in renal or hepatic impaired
patients with intensive glucose monitoring and
the usual dose adjustment on an individual basis
Hospitalised patients
- IDegAsp is not considered suitable for situation in
which rapid inpatient glycaemic control is desired.
- Not the preferred choice for steroid-induced
hyperglycaemia
Pregnancy
There is no clinical experience with the use of
IDegAsp in pregnant woman3
Diabetes in Older Adults :
Management Considerations – ADA 2022

Overall
12.1 Consider the assessment
of medical, psychological,
functional (self management
abilities), and social geriatric
domains in older adults to
provide a framework to
determine targets and
therapeutic approaches for
diabetes management. B
12. 2 Screen for geriatric
syndromes (i.e.,
polypharmacy, cognitive
impairment ,depression,
urinary incontinence, falls,
and persistent pain) in older
adults as they may affect
diabetes self-management
and diminish quality of life B
ADA. Diabetes Care. 2022;45:S1
Neurocognitive Function
12.3 Screening for early
detection of mild cognitive
impairment or dementia should
be performed for adults 65
years of age or older at the
initial visit and annually as
appropriate. B
ADA 2022 – Elderly Management
Hypoglycemia
12.4 Because older adults with
diabetes have a greater risk of
hypoglycemia than
younger adults, episodes of
hypoglycemia should be
ascertained and addressed at
routine visits. B
12.5 For older adults with type
1 diabetes, continuous glucose
monitoring should be considered
to reduce hypoglycemia. . B
Treatment Goal
12.6 Older adults who are
otherwise healthy with few
coexisting chronic illnesses and
intact cognitive function and
functional status should have
lower glycemic goals (such as
A1C <7.0–7.5% [53–58
mmol/mol]),
while those with multiple
coexisting chronic illnesses,
cognitive impairment, or
functional dependence should
have less stringent glycemic
goals (such as A1C <8.0–8.5%
[64–69 mmol/mol]). C

Treatment Goals
Continue
12.7 Glycemic goals for some
older adults might reasonably
be relaxed as part of
individualized care, but
hyperglycemia leading to
symptoms or risk of acute
hyperglycemia complications
should be avoided in all
patients. C
12. 8 Screening for diabetes
complications should be
individualized in older adults.
Particular attention should be
paid to complications that
would lead to functional
impairment. C
ADA. Diabetes Care. 2022;45:S1
12.9 Treatment of hypertension
to individualized target levels is
indicated in most older adults. C
12.10 Treatment of other
cardiovascular risk factors
should be individualized in older
adults considering the time
frame of benefit. Lipid-lowering
therapy and aspirin therapy
may benefit those with life
expectancies at least equal to
the time frame of primary
prevention or secondary
intervention trials. . E
ADA 2022 – Elderly Management
Lifestyle
12.11 Optimal nutrition and protein
intake is recommended for older
adults; regular exercise, incl.
aerobic activity, weightbearing
exercise, and/or resistance training,
should be encouraged in all older
adults who can safely engage in
such activities B
12.12 For older adults with type 2
diabetes, overweight/obesity, and
capacity to safely exercise, an
intensive lifestyle intervention
focused on dietar changes, physical
activity, and modest weight loss
(e.g., 5–7%) should be considered
for its benefits on quality of life,
mobility and physical functioning,
and cardiometabolic risk factor
control. B
Pharmalogic Therapy
12.13 In older adults with type
2 diabetes at increased risk of
hypoglycemia,
medication classes
with low risk of hypoglycemia
are preferred. B
12.14 Overtreatment of
diabetes is common in older
adults and should be avoided. B
12.15 Deintensification (or
simplification) of complex
regimens is recommended to
reduce the risk of hypoglycemia
and polypharmacy, if it can be
achieved within the
individualized A1C target. B
 ADA 2022 – Elderly Management

ADA Recommendations for Glycemic Goals in Older Adults

Patient Characteristics Rationale Reasonable A1C Fasting/Preprandi Bedtime
Goal al Glucose Glucose

Healthy (few coexisting chronic Longer life <7.0% to 7.5% 80-130 mg/dL 80-180
illnesses, intact cognitive expectancy mg/dL
function and functional status)

Complex/intermediate (multiple Intermediate <8.0% 90-150 mg/dL 100-180

coexisting chronic illnesses or life expectancy, mg/dL
2+ instrumental ADL high treatment
impairments or mild to burden,
moderate cognitive impairment) hypoglycemia
vulnerability, fall
risk
Very complex/poor health (LTC Limited life Avoid reliance 100-180 mg/dL 110-200
or end-stage chronic illness or expectancy on A1C; avoid mg/dL
moderate to severe cognitive hypoglycemia
impairment or 2+ ADL and
impairments) symptomatic
hyperglycemia
ADA. Diabetes Care. 2022;45:S1
Key Challenges for T2DM elderly patients
using insulin
 Conceptual: Co-Formulation Insulin will address
problem in elderly patients
Burdensome medical appointments1,2
Simplifying Insulin Therapy
• Multiple and conflicting appointments, particularly
Simple to use
challenging if needing dialysis
• Long waiting room times
• IDegAsp
Lack of close,associated
free parking with simple IDegAsp can be administered anytime
3 with the biggest meals1
• regimen
Appointments&too fewer
short toinjections
address complex needs

Assurance of Hypoglycemia Once daily – might improve

adherence
Co-formulation Insulin contain Insulin IDegAsp administer Once daily can
Degludec with flat and low variability provide FPG & PPG control in one
profile2 injections1

1. Ryzodeg Indonesia Prescribing Information 2022. 2. Heise et al. Diabetes Obes Metab 2012;14:859-64 3. Sajay Karla. Diabetes Ther (2014) 5:65-72

ADA. Diabetes Care. 2022;45:S1

A Japanese Study Assessing Glycemic Control with Use of IDegAsp
Co-formulation in Patients with Type 2 Diabetes in Clinical Practice:
The JAGUAR Study
Study design Retrospective single-arm study using secondary data from MDV (EMR)

BASELINE CHARACTERISTICS Patients using IDegAsp (n=10,798)

Age, mean (SD) 70.37 (11.43)
Age>75, n (%) 3940 (36.5%)
Sex, n (%) female 4625 (42.8%)

Kaneko, Shizuka et al. “A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with Type 2 Diabetes in Clinical Practice: The JAGUAR
Study.” Advances in therapy vol. 38,3 (2021): 1638-1649. doi:10.1007/s12325-021-01623-y
Study Populations JAGUAR study population

Age ≤75 years Age >75 years Total

n=6,858 n=3,940 n=10,798

Age, years, mean (SD) 64.1 ± 9.4 81.4 ± 4.0 70.4 ± 11.4 • Rates of comorbidities were
generally similar between age
Gender, female, n (%) 2,685 (39.2) 1,940 (49.2) 4,625 (42.8)
groups
BMI, kg/m2, mean (SD) 3,507 (51.1) 2,701 (68.6) 6,208 (57.5)

HbA1c, %, mean (SD) 8.4 ± 1.9 8.4 ± 1.7 8.4 ± 1.9 • More patients aged >75 years had
Setting, inpatient, n (%) 24.1 ± 4.8 22.5 ± 4.2 23.4 ± 4.6
a history of hypertension; fewer
patients aged >75 years had a
Diabetes duration, years, mean ± SD 8.5 ± 7.7 9.5 ± 9.3 8.9 ± 8.3
history of retinopathy
History of hypertension, n (%) 4,783 (69.7) 3,135 (79.6) 7,918 (73.3)

History of dyslipidaemia, n (%) 4,635 (67.6) 2,525 (64.1) 7,160 (66.3) • Mean baseline HbA1c was 8.4%,
History of nephropathy, n (%) 2,870 (41.8) 1,573 (39.9) 4,443 (41.1)
suggesting many patients switched
therapies due to poor glycaemic
History of retinopathy, n (%) 2,937 (42.8) 1,359 (34.5) 4,296 (39.8)
control
History of neuropathy, n (%) 1,757 (25.6) 975 (24.7) 2,732 (25.3)

Concomitant medications, mean ± SD 13.3 ± 9.9 16.0 ± 9.6 14.3 ± 9.8 • Only 913 patients had baseline
HbA1c data, and only 4,928 patients
Insulin therapy, pre-mixed, n (%) 3,142 (45.8) 1,705 (43.3) 4,847 (44.9)
had baseline body mass index (BMI)
Insulin therapy, basal–bolus, n (%) 2,575 (37.5) 1,825 (46.3) 4,400 (40.7) data
Insulin therapy, basal, n (%) 1,141 (16.6) 410 (10.4) 1,551 (14.4)

Kaneko, Shizuka et al. “A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with
Type 2 Diabetes in Clinical Practice: The JAGUAR Study.” Advances in therapy vol. 38,3 (2021): 1638-1649.
doi:10.1007/s12325-021-01623-y
Study population by prior therapy JAGUAR study population

Pre-mixed Basal–bolus Basal

n=4,847 n=4,400 n=1,551

Age, years, mean (SD) 70.7 ± 10.6 71.3 ± 11.7 66.7 ± 12.4
• Patients on basal–bolus insulin had a
Gender, female, n (%) 2,086 (43.0) 1,853 (42.1) 686 (44.2)
shorter duration of T2D (6.4 years)
BMI, kg/m2, mean (SD) 23.7 ± 4.5 23.2 ± 4.6 24.4 ± 4.5 than those on basal insulin (9.5 years)
HbA1c, %, mean (SD) 7.9 ± 1.4 8.7 ± 2.2 8.7 ± 1.5 or pre-mixed insulin (10.9 years)
Setting, inpatient, n (%) 2,151 (44.4) 3,553 (80.8) 504 (32.5)
• The basal–bolus subgroup included
Diabetes duration, years, mean ± SD 10.9 ± 8.5 6.4 ± 7.7 9.5 ± 7.7
more inpatients (80.8%) than the pre-
History of hypertension, n (%) 3,669 (75.7) 3,149 (71.6) 1,100 (70.9) mix insulin group (44.4%) or the basal
History of dyslipidaemia, n (%) 3,397 (70.1) 2,592 (58.9) 1,171 (75.5) insulin group (32.5%)
History of nephropathy, n (%) 2,114 (43.6) 1,566 (35.6) 763 (49.2)

History of retinopathy, n (%) 2,049 (42.3) 1,562 (35.5) 685 (44.2)

History of neuropathy, n (%) 1,264 (26.1) 1,020 (23.2) 448 (28.9)

Concomitant medications, mean ± SD 12.2 ± 8.4 17.9 ± 11.1 10.6 ± 6.1

Kaneko, Shizuka et al. “A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with Type 2 Diabetes in Clinical Practice: The JAGUAR
Study.” Advances in therapy vol. 38,3 (2021): 1638-1649. doi:10.1007/s12325-021-01623-y
Switched to IDegASp improved HbA1C JAGUAR study population

over 12 months 0

Patients who SWITCHED to IDegAsp

-1.17* -1.23*
experienced significant reductions in
[VALUE]*
-0.5 [-1.4, -0.94]† [-1.43, -1.02]† HbA1c at 12 months, regardless of age
Change from baseline in HbA1c (%)

[[CELLREF],
[CELLREF]]† n=227 n=364
group
n=137

-1

-1.5

>75 years ≤75 years Total

-2
† 95% confidence interval. * p<0.001.

Least-squares mean differences from baseline calculated using a mixed model repeated measurements analysis, with time in months after
the index date as a fixed factor. The analysis employed an unstructured covariance matrix, including baseline HbA1c, time from baseline
(grouped by month), previous insulin treatment, age, gender, T2D duration, and body weight as covariates.
Kaneko, Shizuka et al. “A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with Type 2 Diabetes in Clinical Practice: The JAGUAR
Study.” Advances in therapy vol. 38,3 (2021): 1638-1649. doi:10.1007/s12325-021-01623-y
Patients on IDegAsp were more likely to JAGUAR study population

meet HbA1c targets than at baseline1

HbA1c <8% HbA1c <7.5% HbA1c <7%
100 RR 1.28 RR 1.24 RR 1.38 100 RR 1.37 RR 1.29 RR 1.57 100 RR 1.53 RR 1.47 RR 1.67
[1.15, 1.43] 95% [1.09, 1.41] 95% [1.13, 1.68] 95% [1.18, 1.60] 95% [1.08, 1.55] 95% [1.16, 2.09] 95% [1.20, 1.94] 95% [1.10, 1.96] 95% [1.10, 2.53] 95%
CI CI CI CI CI CI CI CI CI
Proportion of patients (%)

Proportion of patients (%)

Proportion of patients (%)

80 P<0.001 P=0.001 P=0.002 80 P<0.001 P=0.005 P=0.002 80 P<0.001 P=0.010 P=0.017

60 60 60

40 40 40

20 20 20

0 0 0
n=913 n=442 n=571 n=292 n=342 n=150 n=913 n=442 n=571 n=292 n=342 n=150 n=913 n=442 n=571 n=292 n=342 n=150
Total <75 years >75 years Total <75 years >75 years Total <75 years >75 years

Baseline (pre-index) IDegAsp (post-index)

Regardless of age, Japanese patients were significantly more likely to meet all glycaemic targets 12 months after switching to IDegAsp

Kaneko, Shizuka et al. “A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with Type 2 Diabetes in Clinical
Practice: The JAGUAR Study.” Advances in therapy vol. 38,3 (2021): 1638-1649. doi:10.1007/s12325-021-01623-y
 Patients on IDegAsp experienced less JAGUAR study population

hypoglycaemia than at baseline after 1 year1

Favours IDegAsp Age ≤75 years Age >75 years Total
(n=6,858) (n=3,940) (n=10,978)

Baseline 0.07 0.17 0.10

[CELLREF]

12 months 0.06 0.15 0.09

[CELLREF] Hypoglycaemic events
per participant-year Rate ratio [95% 0.81 0.87 0.83
[CELLREF] CI] [0.70, 0.94] [0.76, 0.99] [0.75, 0.91]

P value 0.006 0.041 <0.001

0.6 0.7 0.8 0.9 1 1.1

Rate ratio

At 12 months, significantly fewer patients switching to IDegAsp had experienced at least one
hypoglycaemic event
(2.6% in the year prior; 2.1% in the year after; RR, 0.80; p=0.011)

Kaneko, Shizuka et al. “A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with Type 2 Diabetes in Clinical
Practice: The JAGUAR Study.” Advances in therapy vol. 38,3 (2021): 1638-1649. doi:10.1007/s12325-021-01623-y
 Jaguar Study Conclusion
HbA1C Hypoglycaemia

• IDegAsp improves glycaemic control in • Rate of hypoglycaemic events decreased

patients previously on insulin in Japanese after IDegAsp initiation
clinical practice
• Results are consistent in the elder
• Results are consistent in the elder population
population
• Low risk of hypos remains consistent after
• Glycaemic improvement remains one titration period
year after initiation

Kaneko, Shizuka et al. “A Japanese Study Assessing Glycemic Control with Use of IDegAsp Co-formulation in Patients with Type 2
Diabetes in Clinical Practice: The JAGUAR Study.” Advances in therapy vol. 38,3 (2021): 1638-1649. doi:10.1007/s12325-021-01623-y
Summary
Summary
• IDegAsp is the first co-formulation insulin PK & PD did not affected by increasing degree
of renal impairment

• From the case report: IDegAsp is a useful options for patients with renal impairment,
including patients undergoing dialysis.

• Diabetes management in elderly should consider holistic approach; neurocognitive

function, treatment goals, hypoglycemia, lifestyle & pharmacologic therapy

• From the Jaguar study: switching to IDegASp improved glycemic control and reduce risk
of hypoglycemia
 56

START with CONFIDENCE

Benefits of initiation with IDegAsp than Insulin glargine

OD 
HbA1c

Simple to use Superior Glycemic Numerical lower Flexibility in the

OD with largest Control risk of Nocturnal timing of insulin
meals1 IDegAsp targeting Hypoglycemia2 adminstrations1
FPG & PPG2

FPG, fasting plasma glucose; HbA1c, glycosylated haemoglobin; PPG, postprandial plasma glucose.
1. Ryzodeg® indonesia Prescribing Information 2022. 2. Onishi, et al. Diabetes Obes Metab 2013;15:826–32.
IDegAsp Latest Safety Update - 30th March 2021
Method of administration
Injection sites should always be rotated within the same region in order to reduce the risk of lipodystrophy and cutaneous amyloidosis (see sections 4.4 and 4.8).

4.4 Special warnings and precautions for use

Skin and subcutaneous tissue disorders
Patients must be instructed to perform continuous rotation of the injection site to reduce the risk of developing lipodystrophy and cutaneous amyloidosis. There is a
potential risk of delayed insulin absorption and worsened glycaemic control following insulin injections at sites with these reactions. A sudden change in the injection site to
an unaffected area has been reported to result in hypoglycaemia. Blood glucose monitoring is recommended after the change in the injection site from an affected to an
unaffected area, and dose adjustment of antidiabetic medications may be considered.

4.8 Undesirable effects

System organ class Frequency

Skin and subcutaneous tissue Not known – Lipodystrophy
disorders Not known – Cutaneous
amyloidosis†

† ADR from postmarketing sources.

Skin and subcutaneous tissue disorders

Lipodystrophy (including lipohypertrophy, lipoatrophy) and cutaneous amyloidosis may occur at the injection site and delay local insulin absorption. Continuous rotation of
the injection site within the given injection area may help to reduce or prevent these reactions (see section 4.4).

Notes:
This slide contain information of IDegAsp latest safety update only. For full information on IDegAsp, please refer to latest updated PI.