1) Basal insulin is recommended as the initial injectable therapy for patients with type 2 diabetes not adequately controlled on oral antidiabetic drugs alone due to the progressive nature of the disease. Basal insulin provides glycemic control through mimicking the basal insulin levels in a physiological manner with a simple regimen. 2) Treatment with basal insulin should start at a dose of 0.1-0.2 units/kg or 10 units daily and be titrated up based on fasting blood glucose levels to achieve target levels while monitoring for hypoglycemia. 3) If glycemic control remains inadequate on basal insulin alone, treatment can be intensified through the addition of other agents such as prandial insulin

1. How To Change Treatment from
OAD to Insulin in Type 2 DM
Banjarmasin Endocrine Update 2022
Workshop

2. *In an observational, retrospective analysis of insulin-naïve patients (N=40,627) with T2DM initiating basal insulin in five European countries and the US.5 HRQoL,
health-related quality of life; QoL, quality of life; T2DM, Type 2 diabetes mellitus
1. Berard L, et al. Diabetes Obes Metab. 2018;20:301–308; 2. Khan H, et al. Prim Care Diabetes. 2011;5:251–255; 3. Hayes A, et al. Value Health. 2016;19:36–41; 4.
Cannon A, et al. J Manag Care Spec Pharm. 2018;24(9a Suppl):S5–S13; 5. Mauricio D, et al. Diabetes Obes Metab. 2017;19:1155–1164.
T2DM is a Progressive Disease
Insulin resistance
Metabolic Syndrome
Beta cells dysfunction
Genetic
factors
Environmental
factors
+
+
β-cell
function
(%)
Treatment optimisation and intensification
Lifestyle + OADs
Basal and 1–3 injections of bolus or premix
Basal insulin + OADs
Titrate dose to reach/maintain glycaemic targets
Intensify for mealtime insulin
coverage
Initiate
Optimise
Intensif
y

3. Injectable therapy is needed due to the progressive
nature of T2D, What to choose?
Due to the
progressive nature
of T2D, many
individuals not
controlled with
OADs will require
advancement to
injectable therapy1–3
GLP-1 RA Basal inulin
+ /- GLP-1 RA or FRC
Fixed-ratio combinations
of basal insulin and GLP-1 RA
Premix insulin
Basal +
prandial insulin
Initial injectable therapy
NICE recommend
premix insulin as an initial injectable
in those with HbA1c ≥9 %3
BI or combined injectable therapy can
also be considered as first injectable
therapy, depending on patient profiles1,2
ADA/EASD generally
recommend GLP-1 RA as
a first injectable option1,2
Premix insulin
Intensification of injectable therapy1–3

4. Mimicking normal
pharmacokinetic profile of
endogeneous insulin
secretion
Principle of Insulin Replacement Therapy

5. Prandial
(meal-related)
Hyperglycemia
Fasting
Hyperglycemia
Basal Insulin
Deficiency
Prandial Insulin
Deficiency
Pathophysiology of Hyperglycaemia
In Diabetes

6. References: 1. Lau ANC, et al. CMAJ. 2012 Apr 17; 184(7): 767–776; 2. Philis-Tsimikas A. Am J Med. 2013 Sep;126(9 Suppl 1):S21-7.
Why use Basal Insulin as the First Insulin in
T2DM Patients?
Simple and convenient
treatment regimen2
More physiological2
Flat action profiles
lasting up to 24 hours2
Reduces glucotoxicity2
Better glycemic control1
Lower risk of hypoglycemia1
Lower weight gain1
Higher adherence1
Basal
Insulin

7. 1.5
Sulfonylureas
1.5
Metformin
1.0-1.5
Glinides
0.5-1.0
DPP-IV
inhibitors
0.8-1.0
TZDs
≥2.5
Insulin
0.0
0.5
1.0
1.5
2.0
2.5
3.0
HbA
1c
reduction
(%)
a
0.5-1.0
GLP-1
RAs
SGLT-2i
0.7-1.0
aEfficacy as monotherapy.
DPP, dipeptidyl peptidase; GLP-1 RAs, glucagon-like peptide-1 receptor agonists.
Adapted from Nathan DM. N Engl J Med. 2007;356:437-440 and Nathan DM et al. Diabetes Care. 2009;32:193-203.
Efficacy as Monotherapy of Antidiabetic Drug

8. Multifaceted Benefits of Timely
Initiation of Insulin Therapy
Preserves β-cell mass
and function
Effectively controls the glucotoxic
effects of hyperglycemia
Improves insulin
sensitivity
Protects against endothelial
dysfunction and damage
that cause vascular disease
Provides long-term
protection to end organs
via ‘metabolic memory’
Alters the course
of disease
progression in a
positive manner
Owens D. Diabetes Technol Ther. 2013;15(9):776–785.

9. Time of day (hours)
400
300
200
100
0
6 6
10 14 18 22 2
Plasma
glucose
(mg/dl)
Normal
Meal Meal Meal
20
15
10
5
0
Plasma
glucose
(mmol/l)
Hyperglycaemia due to an increase in fasting glucose
T2DM
Rationale of using basal insulin in T2DM
Riddle M et al., Diabetes Care, Volume 34, December 2011,2508-2514
Polonsky K, et al. N Engl J Med 1988;318:1231―1239.
Baseline HbA1c ranges
24% 22% 21% 21% 20%
76% 78% 79% 79% 80%
0
20
40
60
80
100
≥9.5
9.0-9.4
8.5-8.9
8.0-8.4
<8.0
Total
Hyperglycemia
(%)
Postprandial hyperglycemia Fasting hyperglycemia
On OAD therapy, fasting (basal) hyperglycemia dominates
over a wide range of HbA1c
Pooled baseline data from 6 Treat-to-Target studies (n=1699 T2DM patients on diet ± OADs). Mean HbA1c
8.69%, FPG 10.8 mmol/L (194 mg/dL). Calculations assume hyperglycemia is >5.6 mmol/L (100 mg/dL)

10. PEDOMAN PENGELOLAAN DAN PENCEGAHAN DIABETES
MELITUS TIPE 2 DEWASA DI INDONESIA - 2021
Sasaran Kendali Glukosa Darah : HbA1C < 7% (individualisasi)
MODIFIKASI GAYA HIDUP SEHAT
HbA1C saat diperiksa
<7.5%
HbA1C saat diperiksa
≥7.5%
HbA1C saat diperiksa
>9%
MONOTERAPI dengan salah satu
dibawah ini
Metformin
Bila HbA1C
belum
mencapai
<7% dalam 3
Bulan,
tambahan
obat ke 2
(kombinasi 2
obat)
Sulfonilurea/Glinid
Penghambat
Glukosidase Alfa
Tiazolidinedion
Penghambat DPP-IV
Penghambat SGLT-2
Agonis GLP-1
KOMBINASI 2 Obat dengan mekanisme
yang berbeda
Metformin
atau
obat
lini
pertama
yang
laiin
Sulfonilurea/Glinid
Bila HbA1C
belum
mencapai <7%
dalam 3 Bulan,
tambahan
obat ke 3
(kombinasi 3
obat)
Penghambat
Glukosidase Alfa
Tiazolidinedion
Penghambat DPP-IV
Penghambat SGLT-2
Basal Insulin
Agonis GLP-1
KOMBINASI 3 Obat
Metformin
atau
obat
lini
pertama
yang
laiin
OBAT
LINI
KEDUA
Sulfonilurea/Glinid
Bila HbA1C
belum mencapai
<7% dalam 3
Bulan, tambahan
obat insulin atau
intensifikasi
terapi insulin
Penghambat
Glukosidase Alfa
Tiazolidinedion
Penghambat DPP-IV
Penghambat SGLT-2
Basal Insulin
Agonis GLP-1
Kombinasi 3 Obat
Kombinasi 2 Obat
atau Insulin ±
Obat lain
Tambahkan Insulin atau
intensifikasi insulin
Gejala klinis (+)
Gejala klinis (-)
Algoritma Pengobatan DM Tipe 2
1. Pemilihan dan penggunaan obat mempertimbangkan factor pembiayaan, ketersediaan obat, efektifitas, manfaat kardiorenal, efek samping, efek terhadap berat badan, serta pilihan pasien
2. Pengelolaan bukan hanya meliputi gula darah, tetapi juga penanganan factor-factor resiko kardiorenal lain secara terintegrasi
3. Obat Agonis GLP-1 dan Penghambat SGLT-1 tertentu menunjukan manfaat untuk pasien dengan komorbid penyakit kardiovaskuler aterosklerotik, gagal jantung dan gagal ginjal. Kedua golongan obat ini
disarankan menjadi pilihan untuk pasien dengan komorbid/komplikasi penyakit tersebut
4. Bila HbA1C tidak bisa diperiksa maka sebagai pedoman dapat dipakai glukosa rerata yang dikonversikan ke HbA1C (poin 7 penjelan algoritma)
PERKENI merekomendasikan dapat mulai insulin basal
• HbA1c > 7.5% dikombinasikan dengan +/- metformin atau agen non-insulin lainnya
• Awal : 0.1-0.2 u/kg BB setara 5-10 unit /hari (BB= 50 kg)
• Penyesuaian: 10-15% atau 2–4-unit, 1-2 kali/minggu sampai tercapai sasaran GDP
• Hipoglikemia: tentukan dan atasi penyebab, turunkan dosis 10-20% (2-4 unit)

11. Algoritma terapi insulin:
Pasien DMTipe 2 +OHO (mono/dual/tripel) dengan HbA1c >7,5%
INISIASI +OPIMALISASI
BASAL INSULIN
PEMIXEDOD
(sebelum makan malam)
Dosis 10U/hari malam
hari atau0,2U/kgBB
OPTIMALISASI DOSIS
Dosis maksimal 0,5U/kgBB
CO-FORMULATION
Atau
FIXED-RATIOCOMBINATION
I NT E N S I F I KA S I

12. Algoritma terapi insulin:
Pasien DMTipe 2 +OHO (mono/dual/tripel) dengan HbA1c >7.5%
I NT E N S I F I KA S I
GDP atauGD pre-
prandial sarapan
NORMAL;
GD sianghariTINGGI
[+]GLP-1RA [+] PRANDIAL
BASAL-BOLUS
BASAL-PLUS
1→2→3
GDP atauGD pre-
prandial sarapan
TINGGI;
GD sianghari
NORMAL
PEMIXED
BID→TID
GDP atauGD pre-
prandial sarapan
TINGGI;
GD siang hariTINGGI
BASAL-BOLUS

13. Algoritma terapi insulin:
Pasien DMTipe 2 baru + HbA1c >9% atauGDP >250 mg/dL atauGDS >300 mg/dL, diserta
gejala dekompensasi metabolic*
CO-FORMULATION
FIX-RATIOCOMBINATION
Insulin + GLP1-RA
BASAL-PLUS BASAL-BOLUS
IDegAspart IDegLira/IGlarLixi
OPTIMALISASI DOSIS
OD → BID
OPTIMASI DOSIS
OD
Tambahkaninsulin prandialpada
makanterbesar
Insulin basal malamhari
Mulai dosis 4 U/hari
atau 10% dosis insulin
basal
OPTIMASI DOSIS
Tambahkan insulin prandialpada
ketigajadwalmakan
Insulin basal malamhari
Basal: 10U malam
Prandial: 4 U atau 0,1
U/kgBB tiap sebelum
makan
OPTIMASI DOSIS
DEEKSKALASI
I NT E N S I F I KA S I

14. Algoritma terapi insulin:
Pasien DMTipe 2 baru + HbA1c >9% atauGDP >250 mg/dL atauGDS >300 mg/dL, diserta
gejala dekompensasi metabolic*
I NT E N S I F I KA S I
CO-FORMULATION
Atau
FIX-RATIOCOMBINATION
[+] PRANDIAL
BASAL-BOLUS
BASAL-PLUS
BASAL-PLUS
BASAL-PLUS1→2→3
BASAL-BOLUS
DEEKSKALASI

15. ADA/EASD: approach to starting and adjusting insulin in T2DM
ADA, American Diabetes Association;
EASD, European Association for the Study of Diabetes;
T2DM, type 2 diabetes mellitus Inzucchi SE, et al. Diabetes Care 2015;38:140–9.
Basal insulin alone is the most convenient initial regimen,
beginning at 10 U or 0.1–0.2 U/kg, depending on the
degree of hyperglycemia. It is usually prescribed in
conjunction with metformin and possibly one additional
non-insulin agent.
Once insulin is initiated, dose titration is
important

16. AlgoritmaStrategiUmum
Terapi Insulin Rawat Jalan

17. HbA1c (%)
Glukosa darah 1-2
jam PP kapiler/ Peak
Postprandial capillary
plasma glucose
Sasaran Kontrol Glikemik
(PERKENI, 2019)
< 7%
L
80 -130
mg/dL
< 180
mg/dL
HbA1c
Gula darah puasa/
Preprandial capillary
plasma glucose
2-3
unit
2-3
unit
Gula
Darah
Puasa
RWE
2
Pertahankan
dosis
< 80 mg/dL
(atau jika ada gejala
hipoglikemia)
80-130 mg/dL
(atau sesuai dengan
konsensus Perkeni baru)
Setiap 3- 7 hari
>130 mg/dL
Turunkan
Dosis
Basal
Insulin
Naikkan
Strategi penyesuaian dosis basal insulin (PERKENI
2019)
PERKENI, 2019, Pedoman Terapi Insulin pada Pasien Diabetes Mellitus

18. PERKENI. Pedoman Pengelolaan dan pencegahan diabetes melitus tipe 2 dewasa di indonesia 2021
Types of Insulin in Indonesia

19. FORNAS 2021 Terbaru
Insulin basal dapat digunakan
pada pasien DMT2 dengan
HbA1c >7.5% / GDS rerata >169
mg/dL

20. 20
Adapted from Fidler C, et al. J Med Econ 2011;14:646-55.
1Stratton IM, et al. BMJ 2000;321:405-12. 2Holman RR, et al. New Engl J Med 2008;359:1577-89.
Insulin treatment involves
a balance between glycemic
control and hypoglycemia
↓ Complications
Extended follow-up for a further 10
years is associated with2
Any diabetes-
related endpoint
Myocardial
infarction
Microvascular
complications
10
20
30
24%
15%
9%
Each 1% reduction in HbA1c is
associated with1
Any diabetes-
related endpoint
Myocardial
infarction
Microvascular
complications
10
20
30
37%
14%
21%
↑ Complications
↓ Medication adherence
↑ Fear of hypoglycemia
↓ Quality of life
↓ Productivity
↑ Healthcare costs
NEGATIVE
POSITIVE
Hypoglycemia
Glycemic
control
Impact on quality and cost of care
Tight glycemic control
↑ Hypoglycemia
↑ Quality of life
↓ Healthcare costs
Hypoglycemia, a major limiting factor in intensive glycemic control, has a range of
consequences for patients with diabetes and an impact on the healthcare system

21. 21
Aspirasi basal insulin ideal
Bekerja > 24 jam Durasi aksi yang lebih panjang
resiko hipoglikemia yang lebih
rendah
Aksi kerja tanpa puncak
Menurunkan glukosa lebih
stabil
Fleksibilitas pemberian
Variabilitas Glikemik yang rendah
Aksi kerja tanpa puncak,
Durasi aksi yang lebih panjang

22. Case 2: Long-standing T2DM uncontrolled on
Multiple OADs
Initiating Basal Insulin Therapy in
Type 2 Diabetes
Fix Fasting First
OAD: Oral antidiabetics; T2DM: Type 2 diabetes mellitus.

23. Case Presentation
History Patient characteristics Present medication
49-year–old Tn. Asep
 49-year–old Mr. Aaron owns
a restaurant and has a 5-
year history of diabetes
 Complaining of burning pain
and numbness of feet
 Vildagliptin 50 mg BID
 Metformin 500 mg TID
 Glimepiride 2 mg OD
 BMI: 25 kg/m2
 HbA1c: 9.2%
 FPG: 220 mg/dL (12.2 mmol/L)
 PPG: 290 mg/dL (16.1 mmol/L)
 Weight: 74 kg
 eGFR: 65 mL/min/1.73m2
 Examination revealed signs of early
diabetic retinopathy in the left eye
BID: Twice daily; BMI: Body mass index; eGFR: Estimated glomerular filtration rate; FPG: Fasting plasma glucose; HbA1c: Glycated hemoglobin; OD: Once a day; PPG: Postprandial glucose.

24. Primary Challenges Identified in the Patient
Uncontrolled
glycemic levels
for a long
duration
Diabetic
neuropathy and
retinopathy

25. Aaron was counselled, and doctor
realized that insulin needs to be
introduced into his regimen in order
to help him achieve the desired
glycemic control.

26. Management of the Patient
49-year–old Mr. Aaron
Insulin glargine 300 was initiated at
dose of 0.2 U/kg/day
Patient was advised to continue
• Sitagliptin/metformin 50/1000
mg BID
• Glimepiride 2 mg OD
BID: Twice daily; OD: Once a day..

27. Sample Computation :
• Weight in Kg x 0.2 U
• 74 kg x 0.2 U = 14.8 or 15 units
• Starting Insulin Glargine300 dose : 15 units
subcutaneously at bedtime

28. Glycemic Recommendations for Non-
Pregnant Adults with Diabetes
A1c
<7.0%
(53 mmol/mol)
Pre prandial capillary
plasma glucose
80–130
mg/dL
(4.4–7.2 mmol/L)
Peak postprandial
capillary plasma
glucose
<180
mg/dL
(10.0 mmol/L)
American Diabetes Association. Diabetes Care 2021 Jan; 44(Supplement 1): S73-S84.