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Standards of
Medical Care

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Learning Objectives

• Discuss the PERKENI Diabetes Mellitus

National Practice Guidelines/Standards of Care

• Review a summary of the ADA Standards of

Care for preventing, diagnosing and treating
prediabetes and diabetes

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Standards of Care:
PERKENI and ADA

• PERKENI created “Diabetes Mellitus National

Clinical Practice Guidelines” (2015)

• ADA Standards of Medical Care in Diabetes

composes all current and key clinical
recommendations from the ADA

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PERKENI: Standards of Care

• Diabetes care must be:

– Continuous, not episodic
– Proactive, not reactive
– Planned, not sporadic
– Patient centered rather than provider centered
– Population based, as well as individual based
– Team care

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PERKENI: Standards of Care

• Ideal core team members:

– A physician
– A nurse
– A dietician
– at least one of whom is certified diabetes educator

• Other team members will vary according to the patient need,

patient load, organization constraints, resources, clinical
setting and professional skills
– e.g.: podiatrist, pharmacist, psychological or social workers

Mensing C. Diabetes Care 2000:23:682-9.

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PERKENI: Screening

• Screening is conducted on those who have

diabetes risks, but do not show any symptoms
of DM.

• Screening seeks to capture undiagnosed DM

or prediabetes so it can be managed earlier
and more appropriately.

• Mass screening is not recommended considering

the costs, which are generally not followed by
action plan for those who were found abnormal.

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Prevention/
Delay of T2DM

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PERKENI: Diabetes Prevention

Management

Periodic Blood
Pharmacology
Early Detection Lifestyle Changes Glucose & Risk
Therapy Factor Monitoring
High-risk population at • Medical Nutritional • Not yet • Hypertension
>30-year old Therapy recommended
• Dyslipidemia
• Family history of DM • Physical activity
• Cardiovascular disorder • Physical health
• Overweight
• Weight reduction
• Sedentary life style
• Known IFG or IGT • Body weight
• Hypertension • If overweight, control
• Elevated triglyceride, low reduce body
HDL or both weight by 5-10%
• History of Gestational DM
• History of given birth
• Physical exercise
> 4000g
• PCOS for 30 minutes,
5 times/week, or
• 2-hour OGTT is the most 150 minutes/week
sensitive method for early
detection and a
recommended screening
test procedure

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Prevention program

GHS / Obat DM & comorbid

treatment
GHS

Risk
In Health
Factors(+) Diagnosed DM

Complications (+)

Primordial
Primary
Seconder
Tertiary

Prevention programs

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Diagnosis

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Screening/Testing
for Diabetes in
Asymptomatic Patients

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PERKENI Guidelines 2015

FBG = Fasting Blood Glucose
Diabetes Symptoms RBG = Random Blood Glucose
IGT = Impaired Glucose Tolerance
IFG = Impaired Fasting Glucose

Diabetes Classic Symptoms (+) Diabetes Classic Symptoms (-)

FBG ≥126 <126 FBG ≥126 100-125 <100

atau atau

RBG >200 <200 RBS >200 140-199 <140

FBG and PPG

FBG >126 <126

atau OGTT 2 hour BG
RBG ≥200 <200

>200 140-199 <140

Diabetes Mellitus
IGT IFG Normal

Evaluation of Nutritional Status Education

Evaluation Diabetic Complications Dietary Planning
Evaluation Dietary Need and Dietary Planning Physical Exercise
Achieving Ideal Body Weight

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PERKENI: Diagnostic
Criteria for Diabetes Mellitus
• Classic symptoms of diabetes + random glucose plasma level
≥ 200 mg/dL. Random glucose plasma level is a test which access
glucose plasma level at a single time without concerning about last
meal schedule.
or
• Classical symptoms of diabetes + fasting plasma glucose
≥ 126 mg/dL. Fasting means patients not getting intake calories
for minimum 8 hours.
or
• 2-h plasma glucose at glucose tolerance test ≥ 200 mg/dL.
Glucose tolerance test done by the WHO standard using 75g
anhydrous glucose which solvent in the 100 cc water
or
• HbA1c ≥ 6.5%
PERKENI GUIDELINES 2015-

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PERKENI: Standard Values of Random Blood

Glucose and Fasting Blood Glucose for
Screening and Diagnosis of DM (mg/dL)

Non DM Uncertain DM DM
Random Venous <100 100-199 ≥200
blood glucose plasma
level Capillary blood <90 90-199 ≥200
(mg/dL)
Fasting blood Venous <100 100-125 ≥126
glucose level plasma
(mg/dL) Capillary blood <90 90-99 ≥100

Note:
For high-risk groups which show no abnormal results, the test should be done
every year. For those aged > 45 years without other risk factors, screening can
be done every 3 years.

PERKENI GUIDELINES 2015

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HbA1c

• Check at first visit

– Used as tool for diagnosis (≥6.5%)
• Every 3 months later on (at least every 6 months)
– For blood control evaluation

PERKENI GUIDELINES 2015

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Diabetes Care

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Target of Treatment

Risk CVD (-) Risk CVD (+)

BMI (kg/m2) 18.5 – <23 18.5 – <23
Blood Glucose
• FPG (mg/dL) <100 <100
• Post Prandial BG (mg/dL) <140 <140-180
A1C (%) <7.0 <7.0
Blood Pressure <130/80 <130/80
Lipid
Total Cholesterol (mg/dL) <200 <200
Triglyceride (mg/dL) <150 <150
HDL Cholesterol (mg/dL) >40 / >50 >40 / >50
LDL Cholesterol (mg/dL) <100 <70

PERKENI GUIDELINES 2015

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Strategies for Improving

Diabetes Care

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Diabetes Self-Management

Team Care: Role of Team Members

Physician
To prepare people with
Nurse diabetes to make
Dietitian self-management
decisions on their own
Educator
People with diabetes
are at the center of
the health team and
can learn to
self-manage
their diabetes

Who’s teaching the diabetics? Etzwiler DD. Diabetes 1967:16:111-7.

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PERKENI: Patient Education

• Daily activities
– Be active most of the time
– Be productive
• Self-management skills
– Preparing pills, insulin
– Follow drug schedule
– Side effect awareness
• Foot care
– Daily foot care & appropriate shoes
• Medical checkup

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PERKENI: Patient Education

• Healthy eating:
– healthy food choices, food composition (carbs, protein,
fat, fiber)
• Body weight maintenance:
– achieved target of BMI or reduced 5 – 10% of body
weight
• Exercise
• Monitoring:
– self-monitoring of blood glucose, A1C
• Hypoglycemia: awareness & self-treatment

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Self-Monitoring
of Blood Glucose (SMBG)

SMBG: one tool to assess therapy in diabetic patients that

is recommended especially in:

• Patients that will undergo insulin therapy

• Patients receiving insulin therapy
• Patients with A1C level did not reach the target
• Women planned for pregnancy / pregnant women with
hyperglycemia
• Patients with recurrent hypoglycemia.

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Diabetes Management – DiabCare Asia

2008 – Type of Management

Diabetes Management Variable n (%)*

Type of Management
• Diet only -
• OAD Insulin monotherapy 1133 (61.88)
• Insulin monotherapy 317 (17.31) 35
• Insulin and OAD combination 356 (19.44)
• Herbal 5 (0.27)
• None 20 (1.09)
*n = 1785

Soewondo P. Med J Indones 2010;19(4):235-244

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Diabetes Management – DiabCare Asia

2008 – Type of OAD Therapy

Diabetes Management Variable n (%)*

Type of OAD Therapy
• Biguanides 1085 (59.26)
• Sulphonylureas 1036 (56.58)
• Meglinitides 8 (0.44)
• Alpha glucosidase inhibitors 461 (25.18)
• TZDs 51 (2.79)
• Other OADs 48 (2.62)
• Traditional herbal medicines 5 (0.27)
• Double drug fixed dose combination 88 (4.81)

Soewondo P. Med J Indones 2010;19(4):235-244

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PERKENI Guidelines 2015

DM Phase - I Phase - II Phase - III

Lifestyle
Lifestyle
Modification
Modification
+ Lifestyle
Modification
OAD Lifestyle
Monotherapy + Modification
2 OADs +
Combination
2 OADs
Alternative: Combination
• Insulin not available
• Patient preference
Lifestyle +
• Glucose control not optimal Modification
Basal Insulin
+
3 OADs
Notes: Intensive Insulin
Fail: not achieving A1c target < 7% after 2-3 months of treatment Combination
(A1c = average blood glucose conversion, ADA 2010)

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Algoritma Pengelolaan DM Tipe-2 di Indonesia, KONSENSUS PERKENI 2015

MODIFIKASI GAYA HIDUP SEHAT

HbA1C <7.5% HbA1C >7.5% HbA1C >9.0%

Gejala (-) Gejala (+)

Monoterapi* dengan Kombinasi 2 obat* dengan

Kombinasi 2 obat
salah satu dibawah ini mekanisme yang berbeda
Insulin ± obat lain
- Metformin - Agonis GLP1 Kombinasi 3 obat Kombinasi 3 obat
- Penghambat
Metformin atau obat lini pertema yang lain

- Agonis GLP1
DPP4 - Agonis GLP1
- Penghambat
- Penghambat
Metformin atau obat lini pertema yang lain

DPP4 - Tiazolidindion
- Penghambat DPP4
- Penghambat
SGLT2 ** - Tiazolidindion
glukosidase - Penghambat
- Insulin basal
alfa SGLT2 **
2 Obat lini kedua

- SU / Glinid
- Penghambat - Insulin basal Mulai intensifikasi insulin
- Kolesevelam**
SGLT2 ** - SU / Glinid
- Bromokriptin
- Tiazolidindion - Kolesevelam**
QR
- Sulfonilurea - Bromokriptin
- Penghambat
- Glinid QR
glukosidase Keterangan:
Jika HbA1C belum alfa - Penghambat
mencapai <7 glukosidase * Obat yang terdaftar, pemilihan dan
dalam 3 bulan, Jika HbA1C belum penggunaannya disarankan mempertimbangkan
alfa
tambahkan obat mencapai sasaran faktor keuntungan, kerugian dan ketersediaan
ke-2 (kombinasi 2 dalam 3 bulan, Jika HbA1C belum sesuai tabel 11.
obat) tambahkan obat ke-3 mencapai sasaran dalam 3 ** Kolesevelam belum tersedia di Indonesia dan
(kombinasi 3 obat) bulan, mulai terapi insulin Bromokriptin QR umumnya digunakan pada
atau intensifikasi terapi terapi tumor hipofisis
insulin

PERKENI, 2015

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Impact of Intensive Therapy for Diabetes:

Summary of Major Clinical Trials
Study Microvasc CVD Mortality
UKPDS      
  
DCCT /
EDIC*
  

ACCORD   
ADVANCE   
VADT 
Kendall DM, Bergenstal RM. © International Diabetes Center 2009
 
Initial Trial
UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854.
Holman RR et al. N Engl J Med. 2008;359:1577. DCCT Research Group. N Engl J Med 1993;329;977. Long Term Follow-up
Nathan DM et al. N Engl J Med. 2005;353:2643. Gerstein HC et al. N Engl J Med. 2008;358:2545.
Patel A et al. N Engl J Med 2008;358:2560. Duckworth W et al. N Engl J Med 2009;360:129. (erratum:
Moritz T. N Engl J Med 2009;361:1024)
* in T1DM

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Individualized target of therapy

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Suggested goals for Glycemic Treatment in Patients with Type-2

Diabetes
Glycated Hemoglobin Range

Most Intensive Level Factors Least Intensive Level

Approximately 6.0% Approximately 8.0%
Highly motivated, Less motivated, non-
adherent, Psychosocial adherent, less
knowledgeable, strong considerations knowledge, weak self-
self-care capability care capability
Adequate Resources or support inadequate
systems
Low Risk of hypoglycemia High
Short Duration of type-2 DM long
Long Life expectancy Short
None Microvascular disease Advances
None Cardiovascular disease Established
None Coexisting conditions Multiple, severe, or both
Ismail-Beigi. N Engl J Med 366:1319, 2012

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Profiles of Antidiabet Medications

METF DPP-4 I GLP1 RA TZD AGI COL BCR SU/glini INSULIN SGLT2 PRAML
SVL OR de
HYPOs Moderate Moderate
to severe to severe
Neutral Neutral Neutral Neutral Neutral Neutral Neutral Neutral Neutral
Mild

Weight Slight loss Neutral Loss Gain Neutral Neutral Neutral Gain Gain Loss Loss

Renal / GU Contra Exenaitide May More More hypo

indicated Neutral ? contra worsen Neutral Neutral Neutral hypoglyc risk & fluid Infection Neutral
grd 3B,4,5 indicate in fluid emia retention
clr crt<30% retention

GI Sx Moderate Neutral Moderate Neutral Moderate Mild Moderate Neutral Neutral Neutral Moderate

CHF Neutral Neutral Neutral Moderate Neutral Neutral Neutral Neutral Neutral Neutral Neutral

CVD Benefit Neutral Neutral Neutral Neutral Neutral Benefit ? Neutral Neutral Neutral

BONE Neutral Neutral neutral Moderate Neutral Neutral Neutral Neutral Neutral Bone Neutral
bone loss loss?

Few adverse events or possible benefits Used with caution Likelihood of adverse events

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Treatment Approach
Other drugs than metformin can be used as initial treatment in some cases
Type-2 Diabetic Patients Lifestyle intervention + 1st initial drug

A1c not at target

Stringent group Less Stringent group

A1c target <7% A1c target ±8%

Existing A1c and A1c Target of Tx

Gap between existing A1c
and target of Tx > 2% Gap between existing A1c
and target of Tx < 2%

insulin Comorbid Drugs

Recurrent HYPOs Metformin / GLP-1RA / DPP4-inh / AGI / TZD

Overweight / Obese GLP-1RA / DPP4-I / Metformin / AGI

Cardiovascular Diseases Metformin / TZD / incretin Tx (?)

Congestive Heart Failure Insulin / Metformin (±) / Incretin Tx

Chronic Kidney Disease Insulin / DPP4-I or AGI (adjust dose)

Liver diseases Insulin, TZD (hepatosteatosis), DPP4-I (?)

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Treatment Targets

• Controlled DM:
– FBG, PBG, HbA1c, Lipid profile, Blood pressure, Nutrition
status
TREATMENT TARGETS
Parameter Targets
IMT (kg/m2) 18,5 - < 23*
Sistolik BP (mmHg) < 140 (B)
Diastolik BP (mmHg) <90 (B)
Preprandial BG – kapiler (mg/dl) 80-130**
1-2 Hours Postprandial BG kapiler (mg/dl) <180**
HbA1c (%) < 7 (individual) (B)
LDL (mg/dl) <100 (<70 high risk CVD) (B)
HDL (mg/dl) Man : >40; Woman: >50 (C)
Trigliseride (mg/dl) <150 (C)

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Comorbids

1. Dyslipidemia
2. Hypertension
3. Obesity
4. Coagulation defect

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Dyslipidemia in Diabetes Mellitus

 Increases of CVD-risk
 Must be confirm at the time of DM diagnosed
 Lipid profile check annually
 When LDL <100mg/dL; HDL >50 mg/dL;
triglyceride <150mg/dL, repeat again every 2
years

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Dyslipidemia in DM

Treatment Target:
 LDL < 100 mg/dL for DM-patient without CVD
 LDL < 70 mg/dL dor DM-patients with ACS or others
CVD or with multiple risk factors (B)
 30-40% reduction of LDL for intolerance patients to
maximal dose of statin (B).
 TG<150 mg/dl (1,7 mmol/L) (C)
 For TG ≥500 mg/dl (4,51 mmol/L) treat with fibrate to reduce
the risk of pancreatitis
 HDL >50 mg/dl

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Hypertension in DM

Treatment indication:
 Systolic BP> 140 mmHg with/without Diastolic BP
>90 mmHg
 Healthy lifestyle for patients with BP > 120/80
mmHg
 Drugs therapy for patients with BP >140/80mmHg

Targets :
 Systolic BP <140 mmHg; Diastolic BP <90 mmHg.
 Treatment combination when not on target with
monotherapy

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Hypertension

• Non-farmakology:
 Lifestyle modification: reduce BW, exercise, stop
smoking and alcohol, reduce salt (B).

• Farmakology:
 ARB
 ACE-I
 Low dose selective beta-blocker
 Low dose diuretic
 Alfa receptor inhibitor
 CCB

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Obesity and Diabetes Mellitus

 Increases prevalence of obesity in Indonesia

 Obesity (central) correlate with metabolic
syndrome
 Reduce body weight 5-10% by lifestyle
modification

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Anti platelets aggregation

 Low dose aspirin (75-162 mg/day) for primary CVD

prevention
 As secondary prevention for men > 50 y.o or women >60
y.o with ≥ 1 as major risk factor (C).
 Not recommended for patients < 21 y.o (Reye syndrome)
 As secondary prevention for diabetic patients with history of
CVD (A).
 One year therapy of antiplatelet drugs combination may
used for diabetic patients with previous ACS (B).
 Clopidogrel 75 mg/day is used for patients with
contraindicated or allergic to aspirin (B)

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Hypoglycemia

 Hipoglycemia: blood glucose < 70 mg/dl.

 With or without autonomic symptoms
 Whipple’s triad:
 Terdapat gejala-gejala hipoglikemia
 Kadar glukosa darah yang rendah
 Gejala berkurang dengan pengobatan.
 Hypoglycemia due to SU (long acting) must be observed
until 48-72 hours

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Hypoglycemia treatment

Mild hypoglycemia
1. Give simple carbohydrate diit (E)
2. Fat in meal reduce glucose absorption
3. 15–20 g glucose for consiousness patients (E)
4. Check blood glucose after 15 minute, if was not in
target repead oral glucose (E), when on target, ask
patient for taking snack or meal (E).

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Hypoglycemia treatment

Severe Hypoglicemia
1. Sign of neuroglicopenia  D5 or D10 infusion + 100
cc D20
2. Check blood glucose 15 min after D20 bolus, repeat
bolus when blood glucose when target is not achieved
3. Blood glucose measurement 1-2 hourly
4. Identify risk factors of hypoglycemia (E)

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Hypoglycemia prevention

1. Hypoglycemic awareness education

2. SMBG
3. Insulin secretagouge and insulin used (time of
consumption, dose, side effects, monitoring)
4. Hypoglycmic risk factors identification
5. Evaluation of treatment program
6. Change to the less hypoglycemic effect of drugs

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Detection and Diagnosis

Gestational Diabetes
(GDM)

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Gestational Diabetes Mellitus (GDM)

• Diagnosis of GDM based on OGTT (75 g

glucose orally)
• Diagnose:
– FBG ≥ 95 mg/dl; 1 hr PP ≥ 180 mg/dl; 2 hr PP ≥ 150 mg/dl
• Manage by team care
– Objective: to reduce morbidity and mortality of the mother and
the baby
• Target of treatment
– FBG : ≤95 mg/dl
– 2hrPP : ≤120 mg/dl

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Assessment of Common
Comorbid Complications

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Thank You

47

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Dyslipidemia

• Dyslipidemia increases cardiovascular risk

• Check lipid profile in first visit newly diabetic
patient and repeat at least every 1 year
• Target of treatment:
– LDL:
• Without CVD < 100 mg/dl
• With CVD < 70 mg/dl
– HDL:
• Men > 40 mg/dl; women > 50 mg/dl
– TG:
• <150 mg/dl
• Therapy:
– Non pharmacology
– Pharmacology: statin, fibrate, niacin

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Hypertension

• Initiation therapy when BP: >130/80 mmHg

• Target of treatment: 130/80 mmHg
• Therapy:
– Non pharmacology
• Reduce BW
• Exercise
• Stop smoking and alcohol
• Reduce salt intake
– Pharmacology:
• ACE-I
• ARB
• CCB
• Low dose diuretic
• Alpha-receptor blocker

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Anti Platelet coagulation

• Low dose aspirin (75-160 mg/day), is used for:

– Diabetic patients with cardiovascular risk
– Patient > 40 years old
• Not recommended for patient < 21 years old
• Combination with other anti-platelet use for
patient with high risk
• Other anti-platelet is used for patient with
intolerance to aspirin

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Nephropathy

• Assess urine albumin excretion annually

– Persistence micro-albuminuria (30-299 mg/24 hrs)
indicated DN
• Measure albumin/creatinine ratio annually
• Control blood glucose
• Control blood pressure

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Recommendations: Hypoglycemia

• Glucose (15 – 20g) preferred treatment for conscious

individual with hypoglycemia
• Check blood glucose 15 minute after glucose therapy
(oraly/iv)
• Glucagon should be prescribed for all individuals at
significant risk of severe hypoglycemia and
caregivers/family members instructed in administration
• Those with hypoglycemia unawareness or ≥ 1 episodes
of severe hypoglycemia should raise glycemic targets to
reduce risk of future episodes

ADA. V. Diabetes Care. Diabetes Care 2012;35(suppl 1):S27.

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Summary

• According to the most recent PERKENI and

ADA Standards of Care:
– optimal diabetes care requires appropriate and
evidence-based prevention, screening, diagnosis,
treatment and educational strategies.

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Oral Diabetes Drugs in Indonesia

Class Generic Trade name mg/tab Daily dose (mg) Duration of Freq/day Taking
name action (hrs) time
Glibenclamid Daonil 2.5 – 5 2.5 – 15 12 – 24 1–2

Minidiab 5 – 10 5 – 20 10 – 16 1–2
Glipizid
Glucotrol-XL 5 – 10 5 – 20 12 – 16** 1
Diamicron 80 80 – 320 10 – 20 1–2
Gliklazid
Diamicron-MR 30 – 60 30 – 120 24 1
Sulfonylurea
Glikuidon Glurenorm 30 30 – 120 6–8 2–3 Before
Amaryl 1-2-3-4 0.5 – 6 24 1 meal

Gluvas 1-2-3-4 1–6 24 1

Glimepirid
Amadiab 1-2-3-4 1–6 24 1
Metrix 1-2-3-4 1–6 24 1
Repaglinid Dexanorm 1 1.5 – 6 3
Glinide
Nateglinid Starlix 120 360 – 3
Actos 15 – 30 15 – 45 24 1
Not depend
Thiazolidinedione Pioglitazone Deculin 15 – 30 15 – 45 24 1
on meal
Pionix 15 – 30 15 – 45 18 – 24 1

Gluckosidase Glucobay 50 – 100 100 – 300 3

Acarbose First spoon
alpha inhibitor Eclid 50 – 100 100 – 300 3
Glucophage 500 – 850 250 – 3000 6–8 1–3
Metformin
Glumin 500 500 – 3000 6–8 2–3 With/after
Biguanide
Glucophage XR 500 – 750 24 1 meal
Metformin XR
Glumin XR 500 500 – 2000 24 1

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Oral Diabetes Drugs in Indonesia

Class Generic Trade name mg/tab Daily dose (mg) Duration of Freq/day Taking
name action (hrs) time
Vildagliptin Galvus 50 50 – 100 12 – 24 1–2
Not depend
DPP-IV Sitagliptin Januvia 25, 50, 100 25 – 100 24 1
on meal
inhibitors
Saxagliptin Onglyza 5 5 24 1
250/1.25
Metformin + Max dose of
Glucovance 500/2.5 12 – 24 1–2
Glibenclamid glibenclamid 20 mg/day
500/5

Glimepirid + 1/250 2/500 2

Amaryl-Met FDC
Metformin 2/500 4/1000

Fixed Pioglitazone + 15/500 Max dose of With / after

Pionix M 18 – 24 1
combintaion Metformin 30/850 pioglitazone 45 mg/day meal

Sitagliptin + 50/500 Max dose of sitagliptin

Janumet 1
Metformin 50/1000 100 mg/hari

50/500
Vildagliptin + Max dose of vildagliptin
Galvusmet 50/850 12 – 24 2
Metformin 100 mg/hari
50/1000

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Insulin in Indonesia

Insulin Onset of action Peak of action Duration of action

Insulin Prandial (Meal Related)

Insulin Short Acting

Reguler (Actrapid®, Humulin® R) 30-60 minute 30-90 minute 3-5 hrs Vial, pen/cartridge

Insulin Analog Rapid Acting

Insulin Lispro (Humalog®) 5-15 minute 30-90 minute 3-5 hrs Pen/cartridge

Insulin Glulisine (Apidra®) 5-15 minute 30-90 minute 3-5 hrs Pen

Insulin Aspart (Novorapid®) 5-15 minute 30-90 minute 3-5 hrs Pen, Vial

Insulin Intermediate Acting

NPH (Insulatard®, Humulin® N) 2-4 hrs 4-10 hrs 10-16 hrs Vial, Pen/cartridge

Insulin Long Acting

Insulin Glargine (Lantus®) 2-4 hrs No Peak 20-24 hrs Pen

Insulin Detemir (Levemir®) 2-4 hrs No Peak 16-24 hrs Pen

Insulin Campuran

70% NPH 30% Reguler

30-60 minute Dual 10-16 hrs Pen/cartridge
(Mixtard®, Humulin® 30/70)

70% Insulin Aspart Protamin

10-20 minute Dual 15-18 hrs Pen
30% Insulin Aspart (Novomix® 30)

75% Insulin Lispro Protamin

5-15 minute Dual 16-18 hrs Pen/cartridge
30% Insulin Lispro (HumalogMix® 25)

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Properties of anti-hyperglycemic agents

Class Mechanism Advantages Disadvantages Cost
Biguanides • Activates AMP- • Extensive experience • Gastrointestinal Low
kinase • No hypoglycemia • Lactic acidosis
•  Hepatic glucose • Weight neutral • B-12 deficiency
production • ?  CVD • CKD
SUs / • Closes K-ATP- • Extensive experience • Hypoglycemia Low
Meglitinides channels •  Microvasc. risk • Weight gain
•  Insulin secretion • Low durability
• ? Ischemic
preconditioning
TZDs • PPAR-g activator • No hypoglycemia • Weight gain High
•  insulin sensitivity • Durability • Edema / heart
•  TGs,  HDL-C failure
• ?  CVD (pio) • Bone fractures
• ?  MI (rosi)
• ? Bladder ca (pio)

DPP-4 • Inhibits DPP-4 • No hypoglycemia • Modest  A1c High

inhibitors • Increases GLP-1, GIP • Well tolerated • ? Pancreatitis
• Urticaria
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

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Properties of anti-hyperglycemic agents

Class Mechanism Advantages Disadvantages Cost

a-GIs • Inhibits a- • No hypoglycemia • Gastrointestinal Mod.
glucosidase • Nonsystemic • Dosing frequency
• Slows carbohydrate •  Post-prandial • Modest  A1c
absorption glucose
• ?  CVD events
GLP-1 • Activates GLP-1 R • Weight loss • GI High
receptor •  Insulin, • No hypoglycemia • ? Pancreatitis
agonists •  glucagon • ? Beta cell mass • ? Medullary cancer
•  gastric emptying • ? CV protection • Injectable
•  satiety
Insulin • Activates insulin • Universally • Hypoglycemia Varia
receptor effective • Weight gain ble
•  peripheral glucose • Unlimited efficacy • ? Mitogenicity
uptake •  Microvascular • Injectable
risk • Training
requirements
• “Stigma”

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

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First Line of Drugs ADA – EASD 2014

AACE 2012

NICE 2009

IDF 2012

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Type-2 DM Drug Treatment Guideline

HbA1c

<7% <7-8% <8-9% 9-10% >10%

HLS HLS
+
Healthy Lifestyle
Monotherapy HLS
• Reduced BW +
•Healthy Diet Met, SU,
• Exercise AGI, Glinid, 2 drugs HLS
TZD, DPP IV combination +
3 drugs HLS
Met, SU,
combination +
AGI, Glinid,
TZD, DPP IV
Met, SU, 2 drugs
AGI, Glinide, combination
TZD, DPP IV
Met, SU,
AGI, Glinid,
TZD

+ HLS
GSH
Basal Insulin +

Intensive
Insulin *

* Intensive insulin : basal bolus approach Indonesian Society of Endocrinology , 2011

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Treatment approach
DIABETES
< 7% ± 8%
TARGET of TREATMENT (more stringent) (less stringent)

CO-CONDITIONS DRUGS CHOICES

Gap of A1c to target ?

Recurrent HYPOs ?

Overweight / obese ?

Cardio Vascular Disease ?

Congestive Heart Failure ?

Chronic Kidney Disease ?

Liver disease ?

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