Memulai dan

Intensifikasi Insulin

A. MAKBUL AMAN MANSYUR

Devision of Endocrine and Metabolism, Department of Internal Medicine Faculty of
Medicine Hasanuddin University /
RS. UNHAS / RS Dr. Wahidin Sudirohusodo / RS.Grestelina / RS.Akademis / RS.
Ibnu Sina Makassar
2015
 Tujuan Pembelajaran

 Memahami peran insulin dalam pengendalian

glukosa darah
 Meningkatkan kemampuan dalam memulai dan
mentitrasi dosis insulin, menggunakan insulin
basal dan premixed
 Mampu melakukan monitoring dan evaluasi
penggunaan insulin
 Obat – Obatan yang diakui untuk DM
Medications Introduction or FDA approval
Insulin 1921
Inhaled insulin 2006
Sulfonylureas 1946
Biguanides 1957 (metformin 1995)
Glycosidase inhibitors 1995
TZDs
Troglitazone 1997
Pioglitazone 1999
Rosiglitazone 1999
Meglitinides 1997
GLP analogues 2005
Amylin analogues 2005
DPP-IV inhibitors 2006

1. ORAL HYPOGLYCMIC AGENTS

2. INSULINS & GLP Analogue
 Problems with Oral Agents

Only moderately effective (~1% lowering of HBA1c)

Type 2 diabetes is a progressive disease (~1% rise in HBA1c in 4 years)
Over time, most patients will need insulin to control glucose

• Sulfonylureas (e.g., glybenclamide, glipizide, etc.)

– Hypoglycemia (long acting)
– ? CAD
• Metformin
– Lactic acidosis risk
• Renal insufficiency, hypotension, heart failure)
– Gastrointestinal
• Nausea, abdominal pain, diarrhea
• Thiazolidinediones (TZDs or “glitazones”) (e.g.,
rosiglitazone)
– Possible liver toxicity
– Fluid overload, heart failure
– Inability to titrate (very slow onset of action)
 Insulin remains the most efficacious
glucose lowering agent
Decrease in HbA1c: Potency of monotherapy
HbA1c %

Slide 5
Nathan et al., Diabetes Care 2009;32:193-203.
 Treatment therapies for Type 2 diabetes

Premix Premix Insulin Premix

Insulin (Twice-Daily) Insulin
(Once-daily
treat-to-target) (Thrice-Daily)
Lifestyle + +-other
Metformin OAD or
GLP-1
agonists
Basal Basal Basal Basal
Insulin Insulin Insulin Insulin
(Once-daily (Basal + 1 (Basal +2 (Basal + 3
treat-to-target) prandial) prandial) prandial)

HbA1c ≥7.0% HbA1c ≥7.0%, FPG on target, PPG ≥160 mg/dl

Most insulin is initiated when HbA1c >8.5%

Adapted from Raccah et al. Diabetes Metab Res Rev 2007;23:257.
Insulin can be initiated anytime
• Traditionally, insulin had been reserved as the last line of therapy
• Considering the benefits of normal glycemic status,
insulin can be initiated earlier, as soon as is required.

Inadequate + + +
Lifestyle 1 OAD 2 OAD 3 OAD

Initiate Insulin
Indication: 1. Fasting BG > 250 mg/dL
2. Random BG > 300 mg/dL
3. Hb A1c > 10 %
4. Weight loss ++
5. Ketonuria
 Benefits of Insulin Therapy
1. Prevention of acute metabolic crises
2. Quick return to ‘health’
3. ↓ ↓ symptoms of glucosuria and hyperglycemia
4. Sense of well-being
5. Anabolic & anti–catabolic effects of insulin
6. Restoration of -cell function
7. -cell protection from apoptosis & preservation
8. Postponement of ‘Secretory Failure’

One of the greatest medical

breakthroughs of the last century.
8
Indications for Insulin Therapy in
Diabetes

Type 1 Diabetes
Gestational DM
Type 2 Diabetes :
• Severe hyperglycaemia at diagnosis
• To meet glycaemic goals
• Patients who fail to reach target with OAD optimal dosage (3-6
months)
• Secondary failure with OAD
• Underweight / weight loss within short period
• Development of severe hyperglycaemia with ketonaemia and or
ketonuria
• Decompensation due to intercurrent events, including: infection,
surgery, liver or kidney disease, high dosage steroid therapy
Mekanisme kerja Insulin
Insulin Glucose

Insulin
receptor

PPARg
RXR
Synthesis GLUT 4
mRNA

PPRE transcriptio
n
promoter Coding reg

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2nd Ed.
Types of insulin
• Human insulin (Since 1982)
– Short-acting
– Intermediate-acting
– Mixture of short- and intermediate-acting (biphasic)
• Modern insulin (Since 1996)
– Rapid-acting
– Long-acting (basal insulin)
– Mixture of rapid- and intermediate-acting (biphasic)

Insulin

Analouge Human /
(Modern) Traditional

Rapid Premixed
Long Short Inter
Acting Acting Acting mediate
HUMAN INSULIN :

1. Kerja Cepat ( Short Acting):

Human insulin: Humulin®, Actrapid, (from E.coli),
ditandai dengan huruf “R” pada ampulnya
2. Kerja sedang (Intermediate-acting insulin)
NPH - neutral protamine Hagedorn (NPH), protamine
mixed.
ditandai dengan huruf “N”
3. Kerja panjang (Long-acting
insulin)
• ULTRALENTE insulin (extended insulin
zinc suspension)
– Ditandai dengan huruf “U” atau “L”
 HUMAN INSULIN

A chain S S

Gly IIe Val Glu Gln Cys Cys Thr Ser Ile Cys Ser Leu Tyr Glu Leu Glu Asn Tyr Cys Asn

1 5 10 15 21
S S

S S
B chain
Phe Val Asn Gln His Leu Cys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg
Gly
1 5 10 15 20 Phe
Phe

25 Phe
Tyr

Thr
Pro
30 The Lys

• Regular : Poor prandial, poor basal

• NPHL: Poor prandial, fair basal (better with small dose QID, small at daytime, large at
night)
• Ultralente: Fair basal
 Limitations of Human Regular
Insulin
• Slow onset of action
– Requires inconvenient administration:
20 to 40 minutes prior to meal
– Risk of hypoglycemia if meal is further delayed
– Mismatch with postprandial hyperglycemic peak
• Long duration of activity
– Up to 12 hours duration
– Increased at higher dosages
– Potential for late postprandial
hypoglycemia
480 80

Plasma glucose
70
400
60

320
50

240 40

30
160
20
80
10

0 0

07.00 12.00 18.00 24.00 07.00

= Short acting human Insulin

Insulin Analogs:

• Insulin Lispro (Humalog®) (1996)

• Insulin Aspart (Novo Rapid®) (2000)
• Insulin Glargine (Lantus®) (2002)
• Insulin Detemir (Levemir®) (Jun.,2005)

• Insulin Glulisine (Apidra®) (Jan., 2006)

Structure of insulin analog:
Aspart, glulisine, lispro, Detemir, glargine

Rapid-Acting Long-Acting
Insulin Insulin

Aspart Glargine

Glulisine Detemir

Lispro
480 80
Plasma glucose
400 70

60
320
50
240
40

160 30

20
80
10

0 0

07.00 12.00 18.00 24.00 07.00

= Insulin analogues Apidra

 Pharmacokinetics of the different Types
of Insulin available in Indonesia
Profile
Onset Peak
Type of Insulin Insulin Name
(hours) (hours)
Fast-acting Analogue Insulin Insulin Aspart (NovoRapid) 0.2 – 0.5 0.5 - 2
Insulin Lispro (HumaLog) 0.2 – 0.5 0.5 - 2
Insulin Gluisine (Apidra) 0.2 – 0.5 0.5 - 2
Fast-acting Human Insulin ActRapid 0.5 – 1 0.5 - 1
Humulin R 0.5 – 1 0.5 - 1
Intermediate Human Insulin Insulatard 1.5 – 4 4 - 10
Humulin N 1.5 – 4 4 - 10
Long-acting Analogue Insulin Insulin Detemir (Levemir) 1-3
Insulin Glargine (Lantus) 1-3
Pre-mix Analogue Insulin Insulin Aspart (NovoMix) 0.2 – 0.5 1-4
Insulin NPL (HumaLog) 0.2 – 0.5 1-4
Pre-mix Human Insulin Mixtard 0.5 – 1 3 - 12
Humulin Mix 0.5 – 1 3 - 12
Slide 19
Adapted from Mooradian et al. Ann Intern Med 2006; 145: 125-34
 Insulin Analogues compared with Human
Insulins: Action Profiles

RAPID-ACTING: Aspart, glulisine, lispro 4–5 hours

Plasma
insulin Regular 6–8 hours
levels NPH 12–20 hours
LONG-ACTING:
Glargine 24 hours
Detemir 20 hours

PRE-MIX INSULIN

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Hours
Goal of Insulin Therapy

We are trying to duplicate

(mimic) how the pancreas
works in releasing insulin
for someone who doesn’t
have diabetes
Mimicking Nature With Insulin
Basal/Bolus Concept
Physiologic Insulin Secretion
24-hr profile
50
(µU/mL)
Insulin

25  Suppresses glucose production

between meals and overnight
0 Basal insulin
 Nearly constant levels
B L D
 50% of daily needs
150
Glucose
(mg/dL)

100

50
Basal glucose
0
7 8 91011121 2 3 4 5 6 7 8 9
AM
Time of Day PM
Adapted with permission from Bergenstal RM et al. In: DeGroot LJ, Jameson JL, eds. Endocrinology.
4th ed. Philadelphia, Pa: WB Saunders Co.; 2001:821
The Basal/Bolus Insulin Concept
• Basal Insulin
– Suppresses glucose production between meals
and overnight non-food related insulin needs.
– 50% of daily needs
• Bolus Insulin (Mealtime or Prandial)
– The amount of insulin required to cover the
food you eat.
– Limits hyperglycemia after meals
– Immediate rise and sharp peak at 1 hour
– 10% to 20% of total daily insulin requirement at
each meal
 Basal and bolus insulin
pharmacodynamics
Formulation Coverage Duration (hr) Dosing
Glargine Basal 24 Once daily
Basal

Detemir Basal 24 Once daily

NPH Basal 13 Twice daily

Lispro Prandial 3–4 ≤15 min premeal to

immediately postmeal
Aspart Prandial 3–4 ≤15 min premeal to
Bolus

immediately postmeal
Glulisine Prandial 3–4 ≤15 min premeal to
≤20 min postmeal
RHI Prandial 6–8 30 min premeal

RHI = regular human insulin Flood TM. J Fam Practice. 2007;56(suppl):S1-12.

Basal/Bolus Treatment Program with
Rapid-acting and Long-acting Analogs

Breakfast Lunch Dinner

Aspart, Aspart, Aspart,
Lispro Lispro Lispro
Plasma insulin

Glulisine Glulisine Glulisine

Detemir/
Glargine

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
How to
Start?
 ADA/EASD Revised Consensus
Statement (2009)
Tier 1 : Well-validated core therapies
Lifestyle + Metformin Lifestyle + Metformin
+ +
At diagnosis: Basal Insulin Intensive Insulin
Lifestyle
+ Lifestyle + Metformin
Metformin +
Sulphonlyureasa
Choose the insulin basal analogue
Step 1 Step 2 Step 3
Tier 2 : Less well-validated core therapies
as a starter
Lifestyle + Metformin
+ Lifestyle + Metformin
Pioglitazone +
No hypglycemia Pioglitazone
Oedema/CHF +
Bone loss Sulphonylureas
Lifestyle + Metformin
+
GLP-1 agonistb Lifestyle + Metformin
David Nathan et al. No hypglycemia +
Diabetes Care 2009; 32:193-203 Weight loss Basal insulin
Nausea/Vomitting
a A Sulphonylurea other than Glibenclamide or Chlorpropamide b Insufficient clinical use to be confident regarding safety.
KONSENSUS PERKENI 2011

“Fix the Fasting First”

Start with basal insulin
 Memulai dan mentitrasi Insulin Basal

Malam hari atau Pagi hari Insulin kerja

panjang ATAU
Malam Insulin kerja menengah Mulai dg insulin basal suntikan
tunggal,
Dosis harian: 10 U atau 0.2 U/kg
contohnya insulin glargine
Cek
GDP perhari
Jika terjadi hipoglikemia atau
Naikkan dosis 2 U per 3 hari sampai GDP
GDP <3.9 mmol/L (<70 mg/dL),
3.9–7.2 mmol/L (70–130 mg/dL)
Kurangi dosis insulin di malam
Jika GDP >10 mmol/L (>180 mg/dL), hari ≥4 unit, atau 10% jika >60
Naikkan dosis 4 U per 3 hari unit

Lanjutkan regimen dan

cek HbA1c tiap 3 bulan
Nathan DM et al. Diabetes Care 2009;32:193-203.
INSULIN INTENSIFICATION
How do we define insulin
intensification?

INITIATE Starting insulin therapy

Dose titration to ensure that the

OPTIMISE patient receives the maximum benefit
from the prescribed treatment

Modification of the insulin regimen,

INTENSIFY e.g. adding to or changing the therapy in
order to maintain glycaemic control
 Intensifikasi Insulin

• Basal Plus dan Basal Bolus

– Ketika Insulin basal ditambahkan pd obat oral tidak
mencapai target A1C
– Lakukan langkah-langkah penambahan insulin
(Stepwise) dg insulin mealtime
• Basal +1 — suntikan kedua sebelum largest meal
• Basal +2 — suntikan ketiga sebelum 2nd meal
• Basal +3 — suntikan keempat sebelum 3rd meal

PERKENI Consensus, 2011.

 The Basal Plus strategy
using once-daily glargine + once-daily glulisine

• Optimize fasting blood glucose

– Titrate insulin glargine to control fasting BG to as close to normal
levels as possible
• Add once-daily insulin glulisine at the main meal1
to control postprandial BG in candidates with:
– HbA1c >7% to <9% despite optimal titration of glargine2
– And FBG control close to or at target3

1Nathan DM, et al. Diabetes Care 2008;31:1–11; 2Del Prato S, et al. Diabetologia 2008;51 Suppl. 1:S452;
3Sanofi-aventis data on file. Glargine titration optimization: Using algorithms employed by clinical
studies for patients with type 2 diabetes, the target FPG should be ≤100 mg/dL (5.5 mmol/l)
 Basal-plus approach: Stepwise addition of
prandial insulin to a basal insulin regimen

1. Optimise basal insulin dose

2. Identify the main meal of the day
3. Introduce prandial insulin once daily at the main
meal
4. Discontinue concomitant insulin secretagogues
5. Titrate the prandial insulin dose to achieve target
blood-glucose levels
6. Add further prandial insulin injections, as required
 Stepwise addition of insulin
Oral antidiabetic agents

HbA1c (%) Basal insulin

Basal + 1 Bolus
9
Basal + 2
Bolus
8
BASAL-PLUS Basal +
3 Bolus
7

5
 Langkah-langkah pendekatan
pengobatan DMT2
A1C <7.0% Basal
Glukosa plasma sebelum makan 70–130 mg/dl Bolus
Puncak glukosa plasma setelah makan <180 mg/dl Basal
ADA-2012 Basal +
Basal Plus
3 suntikan
Plus 2 suntikan prandial
prandial utk
1 suntikan asupan
Insulin Basal prandial utk glukosa
asupan terbesar
Sehari 1x glukosa
OAD (sampai optimal) terbesar
Monoterapi
atau
kombinasi
Diet dan
olahraga A1C A1C tdk terkendali, GDP sesuai target
Tdk terkendali GDPP>8.8 mmol/l (>160 mg/dl)

Waktu

Konsensus PERKENI 2011 ; Raccah D. Diabetes Ob Met 2008;10:76-82.

Insulin Treatment Optimization
How to Optimize Treatment after Basal Initiation

Basal Insulin Only If glycemic target is not

Start with Basal Usually with OAD reached titrate according to
Insulin 10u / daily Basal Titration Scheme
with meal or before
bedtime. Same
injection time every
Basal Insulin Only If glycemic target is not
day
Usually with OAD
reached within 2-3 months
the intensify Insulin
treatment

Premix Insulin Basal with Prandial Basal Bolus

Usually keep OAD Usually keep OAD Usually keep OAD

Switch to Premix twice-daily. Add Prandial starting Switch to Basal Bolus

Start with equal basal dose, with 4u / day either (3 daily prandial) start
but give 50% per injection once or twice-daily and with 4u / day and titrate
and titrate accordingly titrate accordingly accordingly)

Source: PERKENI Insulin Guidelines 2011

3
38
8
Insulin Titration schemes
Basal and Fast-Acting Insulin
Fasting Blood Glucose
Basal Insulin Titration
Content (mg/dl)
<70 mg/dl Reduce dosage with 2 units
70-130 mg/dl Maintain dosage
BASAL
Increase dosage 2 units per
INSULIN 130-180 mg/dl
3 days
Increase dosage 4 units per
>180 mg/dl
3 days
Once titrated, continue to monitor HbA1c every 3 months

Subsequent pre-meal Fast-acting Insulin

Glucose (mg/dl) Titration
FAST-
Increase by 2 units every 3
ACTING Start with 4 units / day
days until target is reached
INSULIN
When starting Fast-acting Insulin, secretagogues
should be discontinued

Slide 39
BASAL - BOLUS Regimen

Advantages:
The most ideal therapy, has similarity with the profile of insulin
endogen
More superior in blood glucose control
Easy and flexible to adjust the dose of basal or bolus insulin if
patients do some variety in meal contect & timing

Disadvantages:
Burden of injection, up to 4 injection daily
Less patient compliance, unsuitable for patient with low
education or poor motivation
Higher risk of hypo and weight gain

Pfutzner A. Int J Clin Pract. 2009

 New ADA/EASD Position on Sequential Insulin
Strategy in Type 2 Diabetes

Non-Insulin Number of Regimen

Regimes Injections Complexity

Basal Insulin Only

Usually with OAD 1 Low

Basal Insulin + 1 mealtime Pre-mixed Insulin twice-daily 2 Mod.

rapid-acting injection

Basal Insulin + >2 mealtime rapid-acting +3 High

injection

More Flexible Less Flexible Flexibility

Less Convenient More Convenient Convenience*

Inzucci SE, et al. Diabetologia. 2012. * Gumprecht et al. Intensification to to biphasic insulin aspart 30/70. Int J Clin Pract
2009
 Memulai dengan Insulin Premixed

• Sebagai alternatif pengobatan setelah insulin basal-

bolus mencapai dosis yang stabil
– Total basal dan bolus insulin dibagi 2,
50% nya diberikan sbg premixed saat sarapan, dan
50% nya lagi sbg premixed saat makan malam
– Stop sulfonilurea
– Jika dosis ketiga dari insulin premixed diperlukan,
10% dari total dosis premixed dapat ditambahkan
saat makan siang

PERKENI Consensus, 2011.

 Memulai dengan Insulin Premixed

Insulin Premixed dapat digunakan :

 Sebagai Strategi intensifikasi setelah gagal pd insulin basal
 Total Dosis Basal dibagi 2, kemudian 50% nya diberikan
sebagai premixed saat sarapan dan 50% nya lagi
diberikan sebagai premixed saat makan malam
 Stop sulfonilurea dan sesuaikan dosis insulin premixed

PERKENI Consensus, 2011.

 21

Intensifying basal insulin

patients to Premix is simple
In basal insulin patients: start with the same total daily dose1

Others consideration
Intensify to •Titrate the dose preferably once a
week.
unit unit •Administer NovoMix® 30 just
basal insulin NovoMix 30
before meals
Pre- Pre-
Dinner •Continue metformin.
Breakfast
•Discontinue sulfonylureas (SUs).
Split total daily dose 50% 50% •Consider discontinuing TZDs as
Twice daily NovoMix® 30 per local guideline and practice.

Adapted from Unnikrishan1

*Guideline for the recommended dose adjustment included in the NovoMix® 30 SmPC3. 1. Unnikrishnan et al. Int J of Clin
Prac 2009; 63:1571–7; 2. Garber et al. Diabetes Obes Metab 2006;8:58–66; 3. Novo Nordisk. NovoMix® 30 summary of
product characteristics
Guide to intensification
Switching from basal insulin OD or BID to NovoMix® 30

Unnikrishnan AG, et al. Int J Clin Pract. 2009 Nov;63(11):1571-7

Guide to intensification
Switching from NovoMix® 30 OD to BID or BID to TID

• Split the OD dose into

equal breakfast and
dinner doses (50:50)
• BID to TID:
– Add 2–6 U or 10% of
total daily NovoMix® 30
dose before lunch
– Down-titration of
morning dose (−2–4 U)
may be needed after
adding the lunch dose
• Titrate the dose
preferably once a week
• Administer NovoMix® 30
just before meals

Unnikrishnan AG, et al. Int J Clin Pract. 2009 Nov;63(11):1571-7

Titration algorithm for implementing these
guidelines
• This algorithm is taken from
– the INITIATE study and
– the current NovoMix 30 EU label (available online at:
Adjust dose of NovoMix® 30 once a week
http://www.emea.europa.eu/humandocs/PDFs/EPAR/Novomix/H-308-PI-en.pdf)

Pre-prandial BG value Dose change

(mg/dL) (mmol/l)
< 80 < 4. 4 -2 U

80110 4.46.1 -

111140 6.27.8 +2 U

141180 7.910.0 +4 U

> 180 > 10.0 +6 U

Raskin P et al. Diabetes Care 2005;28:260-5

 Startegi Memberikan Pengobatan yg
tepat pada pasien yg tepat
• Karakteristik pasien
– Profil gula darah pasien
– Faktor psikososial dan budaya
– Pilihan Pasien
– Usia
– Penyakit komorbid
– Keinginan utk mematuhi pengobatan

• Karakteristik Insulin
– Kemampuannya utk menyamai sekresi insulin endogen
– Potensi efek samping
– Biaya
– Kompleksitas komposisinya
Meneghini L. South Med J 2007;100:164-74.
Mooradian AD et al. Ann Intern Med 2006;145:125-34.
Hirsch IB et al. Clin Diabetes 2005;23:78-86.
 Insulin Initiation
Provider Concerns

• Which Insulin?
• How Much?
• How do I adjust?
• How do I teach?
• How often do I change
dosages?
 Pertimbangan Dokter dan Pasien
dalam penggunaan Insulin
• Pasien
– Kesulitan untuk mematuhi pengobatan
– Takut akan rasa sakit akibat suntikan
– Kesulitan menggunakan hitungan dosis insulin
– Pertimbangan kegemukan / hipoglikemia
– Takut akan timbulnya luka parut di kulit
• Dokter
– Kurangnya edukasi secara personal untuk penggunaan
insulin
– Kurangnya waktu
– pertimbangan akan kegemukan / hipoglikemi
Polonsky WH et al. Clin Diabetes 2004;22:147-50.
Cefalu WT. Am J Med 2002;113(suppl 6A):23S-35S.
Common Concerns When
Transitioning To Insulin
•Fear of needles or pain from injections
•Fear of hypoglycemia
•Weight gain

•Adverse impact on lifestyle; inconvenient; loss of personal freedom and

independence

•Belief that insulin means diabetes is worse or more serious disease

•Insulin as a personal failure

•Insulin causes complications

•Treated differently by family members

Funnel M. Self-management Support for Insulin Therapy in Type 2 Diabetes.

The Diabetes Educator 2004;30:274
 Mengatasi Hambatan Insulin
Hambatan Intervensi
“Sekali memulai insulin Sarankan untuk mencoba dalam kurun
maka saya tidak pernah waktu tertentu (contoh: 1 bulan),
menghentikannya” kemudian dievaluasi kembali
“Saya belum Insulin bukan suatu hukuman; edukasi
menyelesaikan pasien mengenai progresivitas penyakit
pekerjaan dengan baik” diabetes
“Insulin dapat membuat Edukasi pasien mengenai progresivitas
kebutaan” penyakit diabetes

“Saya takut suntikan” Pertimbangkan insulin pen

Polonsky W et al. Clin Diabetes 2004;22:147-50.

 Insulin dan Waktu Pemeriksaan Gula
Darah Mandiri
Monitoring Gula
Insulin Waktu suntikan Pemberian
Darah

1-2 jam setelah suntikan

Kerja sebelum atau
Setelah makan atau segera sebelum
Singkat setelah makan
makan
Diantara makan/makan Segera sebelum makan
Regular Sebelum makan berikutnya atau pada saat berikutnya; biasanya 1-2
akan tidur jam setelah suntikan

Sebelum sarapan, Diantara makan siang/malam Sebelum sarapan,

Kerja Diantara tengah sebelum tidur, midsleep,
Sebelum makan
Meneng
ah malam, malam/sarapan, dan sarapan, sebelum
pada saat akan tidur Diantara pukul 04:00/sarapan sarapan
Sebelum sarapan,
Kerja Kebanyakan pada malam
atau pada saat akan Sebelum sarapan
Panjang hari
tidur

Medical Management of Type 2 Diabetes. 7th Edition. American Diabetes Association, 2012.
 Pilihan untuk Follow-Up Pasien

• Saat kunjungan / kontrol

• feedback: SMS, social media

• Pasien sendiri yg menyesuaikan

• Follow-up harus sesuai dg kondisi tertentu spt

budaya, ketersediaan teknologi dll

Hirsch IB et al. Clin Diabetes 2005;23:78-86.

 Simpulan

• Pendekatan secara bertahap (stepwise)

direkomendasikan pd pengobatan DMT2
– Naikkan pengobatan dari modifikasi gaya hidup ke
terapi oral, ke insulin, sampai ke intensifikasi dosis,
sesuai kebutuhan
– Inisisasi insulin dimulai dengan pemberin insulin basal
– Edukasi merupakan hal yang sangat penting untuk
menhindari penolakan pasien

• Follow-up untuk monitoring glukosa dan juga

penggunaan insulin untuk menjamin kepatuhan
pada pengobatan
MENYUNTIK INSULIN

• Kebanyakan diberikan subkutan

• Bila area suntikan cukup bersih  tidak
perlu dibersihkan lagi dengan alkohol
• Suntikan intramuskuler mempercepat
absorbsi  secara rutin tidak dianjurkan
• Melakukan pijatan / pemanasan pada
tempat suntikan  mempercepat
absorbsi insulin
TEKNIK MENYUNTIK SUBKUTAN
• Jepit kulit dengan dua jari  tusukkan jarum dengan
posisi 90 derajat  lepaskan jepitan sambil disuntik
 tunggu + 5 detik baru jarum dicabut
• Untuk pasien kurus : arahkan jarum 45 derajat agar
insulin tidak masuk ke otot
• Ketika jarum sudah berada di subkutan, sebelum
disuntikkan tidak perlu dilakukan penyedotan
Lokasi penyuntikan :
1. Lengan atas bagian luar
2. Paha atas bagian depan
3. Abdomen (kec. 2 inci dari pusat)
4. Daerah pantat ( gluteus )
Contoh cara penyuntikan pada abdomen
HumaPen® Ergo II
SoloStar
®
ANALOG INSULIN NOVO NORDISK

NOVORAPID - RAPID ACTING

NOVOMIX - PREMIX

LEVEMIR -LONG ACTING ANALOG

 Contoh Kasus

Pendahuluan
Tn M, usia 50 tahun, suku jawa, memiliki diabetes sudah 4
tahun. Saat ini tidak ada keluhan, namun khawatir dengan
gula darahnya yg tak terkendali. Pada pemeriksaan fisik
TD 130/80 mmHg, Tinggi 167 cm, Berat. Hasil lab terakhir
GDP 210 mg/dl, 2JPP 455 mg/dl, dan A1C 9.5%.

Pasien sdh mengatur makanannya sesuai saran ahli gizi,

dan berolahraga 2x seminggu. Obat yg diminum
glimepiride 1x4mg, metformin 3x500mg, dan selama 2
tahun terakhir,sitagliptin 1x100mg.
 Contoh Kasus

Diskusi
• Bagaimana status kesehatan Tn.M?
• Bagaimana manajemen selanjutnya pada pasien
ini?
• Kapan sebaiknya kita memulai insulin?
 Contoh Kasus

Diputuskan akan memulai insulin.

Diskusi
• Insulin jenis apa yang akan disarankan pada pasien ?
• Dimulai pada dosis berapa?
• Bagaimana menyesuaikan dosis insulin jika
diperlukan?
• Materi edukasi apa saja yang perlu diberikan pada
pasien?
 Contoh Kasus

Tn M kembali
Tn M gula darahnya sdh terkendali selama 6 bulan dengan basal
insulin glargin 14 U sebelum tidur, glimepirid 1x4mg, metformin
3x500mg, namun beberapa minggu lalu gula darahnya naik lagi. A1C
sekarang 9,5%. Berikut hasil glukosa darahnya :

Sebelum Sebelum
Hari Catatan
sarapan makan malam
Minggu 120 285
Senin 160 305 Dosis Glargine ditingkatkan 2 U
Selasa 130 190
Rabu 165 276 Lupa menyuntik Glargine
Kamis 120 289
Jumat 110 233
Sabtu - 312
 Contoh Kasus

Diskusi
• Sebutkan masalah dari Tn.M?
• Bagaimana saran anda untuk manajemen
selanjutnya?
• Bagaimana saran anda untuk penggunaan insulin
selanjutnya?
• Bagaimana penyesuaian dosis insulin yang anda
sarankan?
 Contoh Kasus

Follow-up
•Tiga bulan kemudian Tn.M kembali. A1C sekarang 8,7%. Obatnya
glimepiride 1x4 mg, metformin 3x500mg, glargin 1x14 U sebelum tidur,
glulisine 8 U sebelum makan malam, Gula darahnnya kemudian:

Sebelum Sebelum
Hari Sebelum sarapn Catatan
makan siang makan malam
Minggu 110 190 160
Senin 108 205 154
Selasa 120 198 160
Rabu 115 212 152
Kamis 98 200 170
Jumat 108 180 156
Sabtu 99 190 160
 Contoh Kasus

Diskusi
• Bagaiman status Tn.M?
• Bagaimana saran anda selanjutnya dalam penggunaan
insulin?
 Contoh Kasus

6 bulan kemudian …

Tn M gula darahnya sudah terkendali dengan glulisine

8 U sebelum makan pagi, 8 U sebelum makan siang,
dan 8 U sebelum makan malam, ditambah glargine 14
U sebelum tidur, dan metformin3x 500mg. Pasien
menanyakan kemungkinan untuk menggunakan
insulin yg lebih sederhana.
 Contoh Kasus

Pertanyaan
• Apa yg akan anda sarankan?
• Jika anda menyarankan insulin campuran, (premix)
bagaimana anda menyesuaikan dosis nya?
 Case 2
A 52-year-old man was diagnosed with type 2 diabetes (T2DM)
eight years ago. His current treatment regimen includes basal
insulin (50 units daily), metformin (1,000 mg b.i.d.), and
glimepiride (2 mg daily), as well as lisinopril (10 mg daily), and
atorvastatin (20 mg daily).
Recent blood tests was in normal limits, included lipid levels as
well as renal and liver function, but showed an HbA1c level of
8.3%. Blood pressure 110/80 mmHg. No signs of
cardiovascular disease and BMI of 32 kg/m2. Morning fasting
BG is 135 mg/dl and 2 hours post prandial 178 mg/dl. BG
before evening meal 130 mg/dl and post prandial 198 mg/dl.

• How would you optimise his treatment?

• How would you titrate the dose ?
 Case 3 :Miss Nadia

• Born in 1950
• Diagnosed with type 2 diabetes in 2001
• Started glargine in 2008
• Changed to NovoMix BID® 30/70 insulin in
2010 with metformin 2 x 850 mg
• Manages an active lifestyle gardening
• Had laser therapy once to both eyes for
diabetic retinopathy
 Miss Nadia

• BMI 29.9 kg/m2

• BP: 145/85 mmHg
• Constant micro-albuminuria for years
• HbA1c
– June 2012: 7,1 %
– September 2013: 7,2 %
• No history of hypoglycaemia
• Fasting glucose was 121 mg/dL in October 2013
 Miss Nadia’s 7 point curve

Post- Before Before Post Before

Fasting
BFast lunch
Post lunch
dinner dinner bedtime
HbA1c

6.5 11.8 7.3 8.1 7.0 12.9 8.9

7.2 %
(117) (212) (131) (146) (126) (232) (160)
7.1 14.1 7.1 8.0 6.2 15.9 7.9
--
(128) (254) (128) (144) (112) (286) (142)
Values in mmol/L (mg/dL)
 Which option do you have?

Options:
1. No changes required, HbA1c is OK
2. Change to BIAsp 30 TID
3. Change the patient to basal-bolus
therapy
4. Other
 Thank you
The End!!
Merci
ً‫شكرا‬