People waiting at a diabetes

clinic in Tanzania

Mengenal terapi insulin & manfaatnya

Dr. dr. Sony Wibisono, SpPD, KEMD

 Question
Berikut adalah penyebab diabetes, yakni:

A. Terjadi autoimun
B. Kurangnya jumlah insulin dalam tubuh
C. Tubuh tidak merespon insulin (resistensi insulin)
D. Semua benar
 Definisi Diabetes
Diabetes melitus adalah suatu kelompok penyakit metabolik

dengan karakteristik kadar gula darah yang tinggi, terjadi

karena kekurangan jumlah insulin, kerja insulin atau kedua -

duanya.

Penyebab Diabetes
1. Kekurangan Jumlah insulin

2. Tubuh tidak berespon terhadap insulin ( resistensi insulin )

 T2D treatment optionsand their primary mode of action

Sulphonylureas
Pancreas Glinides
Impaired beta-cell DPP-4 inhibitors
dysfunction GLP-1 RA Kidney
Insulin Glucose
reabsorption

liver
Fat and Muscle
Increased hepatic
glucose output Glucosa Level Insulin
resistance &reduced
glucose uptake

Metformin Metformin
Pioglitazone Pioglitazone
DPP-4 inhibitors (Insulin)
GLP-1 RA
Insulin Gut
Diminished Incretin effect

DPP-4 inhibitors
GLP-1 RA
 Qualitative illustration of the spectrum of factors associated with different forms of DM,
including the variable age at onset, lack of obesity, metabolic syndrome, genetic associations,
different forms of immune changes, C-peptide secretion, and the need for insulin therapy.

Stanley S. Schwartz et al. Dia Care 2016;39:179-186

2016 by American Diabetes Association

 -Cellcentric construct: the egregious eleven.

Stanley S. Schwartz et al. Dia Care 2016;39:179-186

2016 by American Diabetes Association

 Type 2 diabetescharacterized by insulin resistance and
-cell dysfunction1-4
chronic and progressive disease

1. Ramlo-Halsted BA, et al. Prim Care. 1999;26(4):771-789. 2. Piya MK, et al. Br J Clin Pharmacol. 2010;70(5):631-634. 3. DeFronzo RA. Med Clin N Am. 2004;88(4):787-835.
4. Stratton IM, et al. BMJ. 2000;321:405-412.
 Classification of Diabetes
A. Type 1 diabetes
-cell destruction
B. Type 2 diabetes
Progressive insulin secretory defect
C. Gestational Diabetes Mellitus (GDM)
D. Other specific types of diabetes
Monogenic diabetes syndromes
Diseases of the exocrine pancreas, e.g., cystic
fibrosis
Drug- or chemical-induced diabetes
American Diabetes Association Standards of Medical Care in Diabetes.
Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
 Question
Tahun 2015, menurut data IDF, Indonesia menduduki peringkat ke -
...... Sebagai negara dengan populasi diabetes tertinggi

A. 7
B. 8
C. 9
D. 10
Pada tahun 2015, Indonesia menjadi peringkat #7
populasi diabetes tertinggi di dunia

Orang dengan
diabetes
meningkatkan
risiko
7 berkembangnya
berbagai masalah
7 kesehatan yang
serius

Source: International Diabetes Federation. IDF Diabetes Atlas., 6th edition update 2015
.http://www.idf.org/diabetesatlas
Diabetes Rule of Halves di Indonesia

>50%
9.1
10.0 Penderita tidak sadar
memiliki diabetes
10,0
<1%
Mencapai target terapi

7 dari 8
4,6 4,4 Pasien yang
membutuhkan insulin,
0,7 tidak mendapatkannya

14.1 juta
Adalah jumlah pasien
prediabetes, IGT (20-
79)
Source: International Diabetes Federation. IDF Diabetes Atlas, Update 2014
 Question
Di bawah ini adalah gejala hiperglikemia/diabetes yakni:
A. Sering berkeringat
B. Ada luka sukar sembuh
C. Mudah emosi
D. Tidak nafsu makan
Gejala Diabetes
 Prediabetes*
FPG 100125 mg/dL
(5.66.9 mmol/L): IFG
OR

2-h plasma glucose 140199 mg/dL (7.811.0

mmol/L): IGT
OR

A1C 5.76.4%
* For all three tests, risk is continuous, extending below the lower limit of
a range and becoming disproportionately greater at higher ends of the
range.

American Diabetes Association Standards of Medical Care in Diabetes.

Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
 Criteria for the Diagnosis of Diabetes

Fasting plasma glucose (FPG)

126 mg/dL (7.0 mmol/L)
OR
2-h plasma glucose 200 mg/dL
(11.1 mmol/L) during an OGTT
OR
A1C 6.5%
OR
Classic diabetes symptoms + random plasma glucose
200 mg/dL (11.1 mmol/L)

American Diabetes Association Standards of Medical Care in Diabetes.

Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
Risk factors for Prediabetes and T2D

www.diabetes.org/are-you-at-risk
American Diabetes Association Standards of Medical Care in Diabetes.
Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
 Two-Step Strategy

100-g OGTT is performed while patient is fasting.

The diagnosis of GDM is made if 2 or more of the
following plasma glucose levels are met or exceeded:
Carpenter/Coustan or NDDG
Fasting 95 mg/dL (5.3 mmol/L) 105 mg/dL (5.8 mmol/L)
1h 180 md/dL (10.0 mmol/L) 190 mg/dL (10.6 mmol/L)
2h 155 mg/dL (8.6 mmol/L) 165 mg/dL (9.2 mmol/L)
3h 140 mg/dL (7.8 mmol/L) 145 mg/dL (8.0 mmol/L)

American Diabetes Association Standards of Medical Care in Diabetes.

Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24
 Strategies for System-Level Improvement

www.BetterDiabetesCare.nih.gov

Three Key Objectives

1.Optimize Provider and Team
Behavior
2.Support Patient Self-Management
3.Change the Care System
American Diabetes Association Standards of Medical Care in Diabetes.
Promoting Health and Reducing Disparities in Populations. Diabetes Care 2017; 40 (Suppl. 1): S6-
S10
 Mean Glucose Levels for Specified A1C Levels

Mean Glucose
Mean Plasma Glucose* Fasting Premeal Postmeal Bedtime

A1C% mg/dL mmol/L mg/dL mg/dL mg/dL mg/dL

6 126 7.0
<6.5 122 118 144 136
6.5-6.99 142 139 164 153
7 154 8.6
7.0-7.49 152 152 176 177
7.5-7.99 167 155 189 175
8 183 10.2
8-8.5 178 179 206 222
9 212 11.8
10 240 13.4
11 269 14.9
12 298 16.5

American Diabetes Association Standards of Medical Care in Diabetes.

Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56
 Approach to the Management of Hyperglycemia

more A1C less

Patient/Disease Features stringent 7% stringent
Risk of hypoglycemia/drug adverse effects
low high
Disease Duration
newly diagnosed long-standing
Life expectancy
long short
Relevant comorbidities
absent Few/mild severe
Established vascular complications
absent Few/mild severe

Patient attitude & expected

treatment efforts highly motivated, adherent, less motivated, nonadherent,
excellent self-care capabilities poor self-care capabilities

Resources & support system

readily available limited

American Diabetes Association Standards of Medical Care in Diabetes.

Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56
 Glycemic Recommendations for Nonpregnant Adults with Diabetes

A1C <7.0%*
(<53 mmol/mol)
Preprandial capillary 80130 mg/dL*
plasma glucose (4.47.2 mmol/L)
Peak postprandial capillary plasma <180 mg/dL*
glucose (<10.0 mmol/L)

* Goals should be individualized.

Postprandial glucose measurements should be made 12 hours after
the beginning of the meal.

American Diabetes Association Standards of Medical Care in Diabetes.

Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56
 Question
Di bawah ini adalah jenis OHO untuk insulin sensitizer yakni:

A. Metformin
B. Glibenclamide
C. Glimepiride
D. Acarbose
 Add another class of agent best suited to the individual (agents listed in alphabetical order):

Class Relative Hypo- Weight Effect in Cardiovascular Other therapeutic considerations Cost
A1C Lowering glycemia Outcome Trial

-glucosidase inhibitor Rare neutral to Improved postprandial control, GI side-effects $$

(acarbose)

Incretin agents:
DPP-4 Inhibitors Rare Neutral to Neutral (alo, saxa, sita) Caution with saxagliptin in heart failure $$$
GLP-1R agonists to Rare Neutral (lixi) GI side-effects $$$$

Insulin Yes Neutral (glar) No dose ceiling, flexible regimens $-$$$$

Insulin secretagogue:
Meglitinide Yes Less hypoglycemia in context of missed meals but $$
usually requires TID to QID dosing
Sulfonylurea Yes Gliclazide and glimepiride associated with less $
hypoglycemia than glyburide

SGLT2 inhibitors
to Rare Superiority Genital infections, UTI, hypotension, dose-related $$$
(empa in T2DM patients with changes in LDL-C, caution with renal dysfunction
clinical CVD) and loop diuretics, dapagliflozin not to be used if
bladder cancer, rare diabetic ketoacidosis (may
occur with no hyperglycemia)

Thiazolidinediones Rare Neutral CHF, edema, fractures, rare bladder cancer $$

(pioglitazone), cardiovascular controversy
(rosiglitazone), 6-12 weeks required for maximal
effect

Weight loss agent (orlistat) None GI side effects $$$

alo=alogliptin; glar=glargine; saxa=saxagliptin; sita=sitagliptin; lixi=lixisenatide; empa=empagliflozin

 Semakin lama pasien di diagnosis DM,
Maka semakin membutuhkan insulin

UKPDS Study Group Lancet 1998;352:837

American Diabetes Association Standards of Medical Care in Diabetes.
Approaches to glycemic treatment. Diabetes Care 2017; 40 (Suppl. 1): S64-S74
American Diabetes Association Standards of Medical Care in Diabetes.
Approaches to glycemic treatment. Diabetes Care 2017; 40 (Suppl. 1): S64-S74
Insulin
Insulin ditemukan tahun 1921..

Banting & Best mengekstrak insulin

dari pankreas anjing
Membuktikan bahwa insulin dapat
mengontrol gejala diabetes pada
anjing tersebut

Experiments in Toronto University

F Banting, surgeon
C Best, medical college student
30 July 1921
Lalu produksi insulin dimulai..
Tahun 1922, pasien pertama berhasil diterapi..

Insulin digunakan untuk terapi pasien pertama (Leonard Thompson)

Adalah pasien DM tipe 1 yang dapat hidup lebih lama menggunakan terapi
insulin

Pasien J.L.,
Pasien J.L.,
15 February,
15 December, 1922
1923
 Question
Insulin basal/kerja panjang contohnya:

A. NovoRapid
B. NovoMix
C. Levemir
D. Actrapid
 Question
Insulin prandial/bolus/kerja cepat contohnya:

A. NovoRapid
B. NovoMix
C. Levemir
D. Insulatard
Perkembangan Insulin

New Generation
Insulin Analogs

Basal
Insulin Analogs
Advancements

Biphasic
Insulin Analogs

Rapid-acting
Insulin Analogs
2000s
Recombinant
Human
Animal Insulin
Isolation
Insulin
of Insulin
(Banting & Best) Preparations 1990s

1977

1922
Time
Jenis Insulin (berdasarkan durasi kerja)

Rapid Acting / Kerja Pendek

Menurunkan Gula Darah Setelah Makan, contoh :
NovoRapid
Intermediate Acting / Kerja Menengah
Menurunkan Gula Darah Puasa
Long Acting / Kerja Panjang
- Menurunkan Gula Darah Puasa, contoh: Levemir
Premixed / Campuran
Menurunkan Gula Darah Puasa dan Gula Darah
Setelah Makan, contoh: NovoMix
 ---- Insulin endogen

Levemir

---- NovoRapid

NovoMix

Breakfast Lunch Dinner Bed time

Insulin memberikan efek penurunan gula darah yang paling
efektif

Penurunan HbA1c: Potensi dari monoterapi

0.0

-0.5
HbA1c%

-1.0

-1.5

-2.0

-2.5

SU/GLIN

Metformin
TZD
Pramlintide

Exenatide
GLP-1

Insulin
DPPIV inh
AGIs

Adapted from: Nathan D, et al. Diabetes 2007;56(Suppl 1):Abstract 0996-P

Perbaikan kontrol glikemik mengurangi
risiko komplikasi jangka lama
Setiap penurunan 1% HbA1c mengurangi risiko
komplikasi jangka lama

43% 37% 19% 16% 14% 12%

Stroke
Infark Miokard
Gagal
Ekstraksi jantung
katarak
Penyakit
mikrovaskular
Amputasi
ekstremitas
bawah atau
penyakit vaskular
perifer fatal

UKPDS: Stratton et al. BMJ 2000;32:40512

 Levemir Dosis Inisiasi dan titrasi:
3-0-3 Algorithm
Start with Levemir 10 U or 0,1-0,2 U per Kg BB
Dose Adjustment for Each Arm
Mean 3-day FPG (mg/dL)
increase dose
FPG>90 mg/dl (5.0 mm/L) 3 3 units FPG>110 mg/dL (6.1 mmol/L)

FPG target range maintain FPG target range

70-90 mg/dL 0 dose
80-110 mg/dL

FPG <70 mg/dL (3.8 mmol/L) decrease dose FPG <80 mg/dL (4.4 mmol/L)

3 units

Patients who experienced hypoglycemia reduced their daily dose by 3 units

Blonde L et al. Diabetes Obes Metab. 2009; 11(6):623-631.

 Kendali HbA1c yang optimal
Sebuah studi yang melibatkan 477 orang pasien diabetes tipe 2 yang
mulai menggunakan Levemir di Indonesia1

Penurunan HbA1c setelah penggunaan Levemir (%)

*P<0.001
n=372

-2.2*

Insulin naive Levemir

Levemir menurunkan HbA1c 2.2%

1. Soewondo, et al.,2013, Clinical experience with insulin detemir: results from the Indonesian cohort of the
international A1chieve study, Diabetes Research and Clinical Practice 100, suppl. S1 (2013) S47S53
Levemir memiliki risiko hipoglikemia yang rendah
Levemir menurunkan risiko hipoglikemia nokturnal sampai
dengan 65% lebih rendah dibandingkan NPH

NPH vs. Insulin glargine NPH vs. Insulin detemir

-29%

-44%
Insulin Detemir
-53%
Insulin NPH
Relative Risk

-65% Insulin glargine

Riddle et al., 2003 Phillis-Tsimikas et al., 2006

Phillis-Tsimikas. Clin Ther 2006;28(10):156981; Riddle et al 2003. Diabetes Care; 26 (11): 3080-6;
Penambahan berat badan lebih rendah
Pemberian Levemir satu kali sehari berasosiasi dengan penambahan berat badan yang secara signifikan
lebih rendah dibandingkan dengan insulin glargine1,2

Terapi basal bolus Hanya terapi basal

4,0 4,0
3,9 40%
Less
Penambahan berat badan (kg)

Penambahan berat badan (kg)

3,0 3,0

2,3
2,0 2,0

1,6 56%
Less
1,0 1,0

0,7

0,0 0,0
NPH Levemir Glargine
Insulin glargine Levemir

Studi 26 minggu, p<0,005 Studi 52 minggu, p=0,03

Philis-Tsimikas et al 2006 Diadaptasi dari Rosenstock et al 2008

1. Rosenstock, et al.,2008, A randomised, 52-week, treat-to-target trial comparing insulin detemir with insulin glargine when administered as add-on to
glucose-lowering drugs in insulin-naive people with type 2 diabetes, Diabetologia (2008) 51:408416
2. Philis-Tsimikas,et al.,2006, Comparison of Once-Daily Insulin Detemir with NPH Insulin Added to a Regimen of Oral Antidiabetic Drugs in Poorly
Controlled Type 2 Diabetes, Clinical Theurapetic/Volume 20, Number 10, 2006
Pilihan untuk intensifikasi patient centre

Patients Favours basal

Favours premix
characters bolus

Patient preferance Comfortable with more

Prefers fewer injection
regarding number of inj frequent injections

Prefers less frequent Patient preferance Comfortable with more

monitoring regarding SMBG frequent monitoring

Patient ability to inject

(e.g. Cognitive ability,
Poor manual dexterity, need for Good
carer)

TedWu, et al. Diabetes Ther 2015

Intensifikasi dari basal ke basal bolus insulin
Intensifikasi dari basal ke premix insulin (NovoMix)

1:1 total dosis dipindah menjadi BIAsp 30

Bagi dosis menjadi 50:50, sebelum makan pagi dan sebelum makan
malam
Titrasi dosis seminggu sekali
Sulphonylurea dihentikan
Metformin dilanjutkan
Pertimbangkan TZD dihentikan
Sumtikan BiAsp30 segera sebelum makan

Contoh:
Dosis Levemir terakhir 20 U, pasien di intensifikasi menggunakan
NovoMix.
Maka, NovoMix diberikan 2x, masing-masing 10 U di sebelum makan pagi
dan 10 U sebelum makan malam. Levemir dihentikan. SU dihentikan.
Metformin dilanjutkan.

Unnikrishnan et al. Int J Clin Pract 2009;63:15717

Alat suntik insulin baru yang
beredar di Indonesia
Thank you