Update Management DM

• Atherosclerotic cardiovascular disease (ASCVD)—defined as

coronary heart disease (CHD), cerebrovascular disease, or
peripheral arterial disease  leading cause of morbidity and
mortality for individuals with diabetes.
• Common conditions coexisting with type 2 diabetes (e.g.,
hypertension and dyslipidemia) are clear risk factors for ASCVD.
• Numerous studies have shown the efficacy of controlling individual
cardiovascular risk factors in preventing or slowing ASCVD in people
with diabetes.
• Recent studies have found that rates of incident heart failure
hospitalization (adjusted for age and sex) were twofold higher in
patients with diabetes compared with those without.
• For prevention and management of both ASCVD and heart failure,
cardiovascular risk factors should be systematically assessed at least
annually in all patients with diabetes.
• These risk factors include obesity/overweight, hypertension,
dyslipidemia, smoking, a family history of premature coronary
disease, chronic kidney disease, and the presence of albuminuria. 
• The American College of Cardiology/American Heart Association
ASCVD risk calculator (Risk Estimator Plus) is generally a useful tool
to estimate 10-year risk of a first ASCVD event (available online at 
tools.acc.org/ASCVD-Risk-Estimator-Plus).
PHARMACOLOGIC THERAPY FOR ADULTS WITH
TYPE 2 DIABETES
• Recommendations
• 9.4a First-line therapy depends on comorbidities,
patient-centered treatment factors, and management
needs and generally includes metformin and
comprehensive lifestyle modification. A
• 9.4b Other medications (glucagonlike peptide 1
receptor agonists, sodium–glucose cotransporter 2
inhibitors), with or without metformin based on
glycemic needs, are appropriate initial therapy for
individuals with type 2 diabetes with or at high risk for
atherosclerotic cardiovascular disease, heart failure,
and/or chronic kidney disease (Fig. 9.3). A
• 9.5 Metformin should be continued upon initiation of
insulin therapy (unless contraindicated or not
tolerated) for ongoing glycemic and metabolic
benefits. A
• 9.7 The early introduction of insulin should
be considered if there is evidence of
ongoing catabolism (weight loss), if
symptoms of hyperglycemia are present,
or when A1C levels (>10% [86 mmol/mol])
or blood glucose levels ($300 mg/dL [16.7
mmol/L]) are very high. E
• 9.8 A patient-centered approach should
guide the choice of pharmacologic agents.
Consider the effects on cardiovascular and
renal comorbidities, efficacy, hypoglycemia
risk, impact on weight, cost and access,
risk for side effects, and patient
preferences (Table 9.2 and Fig. 9.3). E
1
1

SLIDE DECK

LockStep
Local Scientific Development Program: IDegAsp Co-formulation
IDegAsp Co-formulation
The insulin co-formulation concept

Co-formulation of a basal insulin with a bolus insulin in a

single injection can:

Mimic physiological insulin

secretion closely

Avoid the “shoulder effect”

and variability of protaminated
mix insulin

Physiological insulin profile Simplify the insulin regimen and

Bolus insulin lower the injection burden
Basal insulin

No need resuspension

Atkin S. Ther Adv Chronic Dis 2015; 6: 375–388;

Kruszynska YT et al. Diabetologia 1987; 30: 16–21
IDegAsp: First in class Co-formulation Insulin
[basal insulin with an ultra-long duration of action and a mealtime insulin in one pen 1,2]

Insulin degludec
First basal insulin analogue that can be
combined in a soluble solution with a
mealtime insulin.3 3

1. Heisse et al. DIABETES CARE, VOLUME 34, MARCH 2011. 2. Haarh et al. Clin Pharmacokinet (2017) 56:339–354. 3 Jonassen, et al. Pharm Res (2012)
29:2104–2114 4 5. Heller S, et al. Diabetes Metab Res Rev 2012; 28: 50–61
Clinical guidance on initiation

…Clinical evidence support the study of IDegAsp

…IDegAsp OD to be considered as2,3
initiation of people with T2DM [Onishi]1:

INITIATION (OAD FAILURE)

Superior reduction of HbA1C
PREFERRABLE TO BASAL INSULIN ALONE

Numerical lower risk of Nocturnal

Hypoglycemia 25% • Max OAD therapy but HbA1C >7 and PPG 180 mg/dL

• Extreme and symptomatic Hyperglycaemia

More patient achieve target without
hypoglycemia 2X • Postprandial Hyperglycaemia is a concern

• People with low BMI

• References: 1. Onishi et al. Diabetes Obes Metab 2013;15:826–32 2. Sarah Galtras et al. J Clin Med 2020. 3. Roopa M et al. Diabetes Obes Metab. 2020;1-15
Recommended starting dose for initiations

Starting dose Severe Hyperglycemia

HbA1c >10% (86 mmol/mol)*

10
With largest meals
Unit/OD > 10
With largest meals
Unit/OD

Followed by subsequent INDIVIDUAL dosage

*This posology is based on expert recommendations from
weekly adjustment until the desired FPG
Sarah G et al. reached

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
Suggested once-weekly titration schedule for IDegAsp OD in T2D

Above target
Above target +2 • Dose adjustments based on lowest of
units the 3 preceding FPG measurements

At
At target
individualised Maintain FPG target should be individualised
individualised target dose
Do not increase dose if hypoglycaemia or
symptoms suggestive of hypoglycaemia
Below target
Below target
-2 are present
units

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
 Intensification from IDegAsp OD

If HbA1C is not met with IDegAsp OD, glucose monitoring is needed to determine where
If Adequate glycaemic control is not
hyperglycaemia is occurring.
achieved with
Treatment can be intensified to
TREATMENT INTENSIFICATION

IDegAsp OD

A
IDegAsp (Split dose)
Treatment can be intensified to….

B IDegAsp OD + Iasp at one or

more meals

3 C IDegAsp (split dose) + Iasp at +

the third meals
Alternative Strategy to
achieve adequate
glycaemic control

References: 1. Sarah Galtras et al. J Clin Med 2020. 2. Roopa M et al. Diabetes Obes Metab. 2020;1-15
 IDegAsp Split IDegAsp split + Iasp IDegAsp OD + Iasp

or

When & How

do you
intensify: ‘if post prandial occurs when FPG is normal’
‘if there are post prandial glucose excursion ‘if there are persistent excessive post

after 2 meals’ prandial glucose excursion’

(i.e in country where meals are typically rich

Recommend a max OD dose 30-40 unit before (i.e 3 reading of >180 mg/dL over 1 week on in carbohydrate)

splitting. SMBG/capillary blood glucose)*

The dose ratio not necessarily (1:1) with a

minimum dosing interval of 4 hours

*: this may be vary with individualise target and monitoring frequency

References: 1. Sarah Galtras et al. J Clin Med 2020. 2. Roopa M et al. Diabetes Obes Metab. 2020;1-15
Summary

• There are some challenges in current treatment option, such as 70% patient is failed to achieve target
with basal insulin alone, complexity of treatment and risk of hypoglycaemia

• IDegAsp co-formulation is the only co-formulation insulin contains ultra long-acting basal insulin
degludec and rapid acting insulin aspart

• IDegAsp co-formulation can be used for initiation with benefit of superior HbA1c control and numerical
lower hypoglycaemia compared to IGlar U100
Patient
Reasonable A1C Fasting or
characteristics/heal Rationale Bedtime glucose Blood pressure Lipids
goal‡ preprandial glucose
th status

Healthy (few
coexisting chronic Statin unless
Longer remaining <7.0–7.5% (53–58 80–130 mg/dL (4.4– 80–180 mg/dL (4.4–
illnesses, intact <140/90 mmHg  contraindicated or
life expectancy  mmol/mol)  7.2 mmol/L)  10.0 mmol/L) 
cognitive and not tolerated 
functional status) 

Complex/
intermediate Intermediate
(multiple coexisting remaining life
chronic illnesses* or expectancy, high Statin unless
<8.0% (64 90–150 mg/dL (5.0– 100–180 mg/dL
2+ instrumental treatment burden, <140/90 mmHg  contraindicated or
mmol/mol)  8.3 mmol/L)  (5.6–10.0 mmol/L) 
ADL impairments or hypoglycemia not tolerated 
mild-to-moderate vulnerability, fall
cognitive risk 
impairment) 

Very complex/poor Avoid reliance on

health (LTC or end- A1C; glucose
stage chronic Limited remaining control decisions
Consider likelihood
illnesses** or life expectancy should be based on 100–180 mg/dL 110–200 mg/dL
<150/90 mmHg  of benefit with
moderate-to-severe makes benefit avoiding (5.6–10.0 mmol/L)  (6.1–11.1 mmol/L) 
statin 
cognitive uncertain  hypoglycemia and
impairment or 2+ symptomatic
ADL impairments)  hyperglycemia 
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