Kontrol Diabetes

Andreas Fernandez

Indonesia is One of The Largest Diabetes Population

in The World (2014)
Top 10 Countries/Territories of number
Of people with diabetes (20-79 years), 2014

China

96,2
66,8

India
25,7

USA

11,6

Brazil

Prevalence: 5,55% (adult pop.)

Sources :
1. IDF Diabetes Atlas, 6th ed
2. IDF Diabetes Atlas 6th ed UPDATE

Indonesia

9,1

Mexico

Egypt

7,5

German

7,2

Turkey

7,2

Japan

7,2

Prevalence: 5,55% (adult pop.)

Poor Diabetes Control Leads to

Poor Health Outcomes
Less
than 1%
Less than 1% achieve
targets, it leads to poor
health outcomes

sec

Every 7 seconds
a person dies from
diabetes2

Sources :
1. IDF Diabetes Atlas, 6th edn. Brussels, Belgium: International Diabetes Federation, 2013. http://www.idf.org/diabetesatlas
2. IDF atlas 6 ed UPDATE 2014

Healthy vs T2DM Insulin Secretion

Adapted from: Ramlo-Halsted BA, Edelman SV. Clincial Diabetes 2000;18(2): http://journal.diabetes.org/clinicaldiabetes/v18n22000/pg80.htm

Pathophysiology : The Ominous Octet

Kruger D F et al. The Diabetes Educator 2010;36:44S-72S

Foundations of Care

Education

Healthy diet

Physical activity

Medications

ADA Standards of Medical Care 2015

Recommendations

Diabetes self-management education (DSME)

Diabetes self-management support (DSMS) according to
the national standards
Consistent carbohydrate intake with respect to time and
amount can result in improved glycemic control
Min 150 min/week of moderate-intensity aerobic physical
activity
3 days/week with no more than 2 consecutive days without
exercise.

ADA Standards of Medical Care 2015

Comprehensive Diabetes Evaluation

Team:

Teams role

Doctors
Nurses
Nutritionists
Educators

PATIENT CENTERED
& Independent self
management

Whos teaching the diabetics? Etzwiler DD. Diabetes 1967:16:111-7.

Prepare patients so
they can decide the
treatment for
themselves

Individualized Management of Hyperglycemia

More
stringent

Patient attitude and expected

treatment efforts

Less
stringent

Less motivated, nonadherent,

poor self-care capacities

Highly motivated, adherent,

excellent self-care capacities

Risks potentially associated with

Hypoglycemia & other adverse eventLow
Disease duration

High

Newly diagnosed

Long standing

Life expectancy
Long

Short

Important comorbidities

Esthablished vascular complication

Absent

Few/mild

Severe

Absent

Few/mild

Severe

Resources & support system

Readily available
ADA Standards of Medical Care 2015

Limited

Healthy eating, weight control, increased physical activity & diabetes education

Monotherapy

Metformin

Efcacy*
Hypo risk
Weight
Side effects
Costs

Me ormin
intoleranceor
contraindica on
Dual
therapy

HbA1c
9%

Efcacy*
Hypo risk
Weight
Side effects
Costs

high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Metformin

Sulfonylurea

Thiazolidinedione

DPP-4
inhibitor

high
moderate risk
gain
hypoglycemia
low

high
low risk
gain
edema, HF, fxs
low

intermediate
low risk
neutral
rare
high

Metformin

Metformin

Metformin

Metformin

SGLT2
inhibitor

GLP-1 receptor
agonist

Insulin (basal)

intermediate
low risk
loss
GU, dehydration
high

high
low risk
loss
GI
high

highest
high risk
gain
hypoglycemia
variable

If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):

Metformin

Triple
therapy

Sulfonylurea

+
TZD

Uncontrolled
hyperglycemia

(catabolicfeatures,
BG300-350mg/dl,
HbA1c10-12%)

Metformin

Thiazolidinedione

SU

Metformin

Metformin

DPP-4
Inhibitor

SGLT-2
Inhibitor

SU

SU

Metformin

GLP-1 receptor
agonist

Metformin

Insulin (basal)

+
TZD

SU

or

DPP-4-i

or

DPP-4-i

or

TZD

or

TZD

or

TZD

or

DPP-4-i

or

SGLT2-i

or

SGLT2-i

or

SGLT2-i

or

DPP-4-i

or

Insulin

or

SGLT2-i

or

Insulin

or

Insulin

or GLP-1-RA

or GLP-1-RA

or

or

Insulin

or GLP-1-RA

Insulin

If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:

Metformin

Combination
injectable
therapy

Basal Insulin +

Mealtime Insulin or

GLP-1-RA

Diabetes Care 2015;38:140-149; Diabetologia 2015;10.1077/s00125-014-3460-0

15

Sasaran Pengendalian DM
Parameter

Sasaran

BMI (kg/m2)

18,5 - < 23 *

TDS (mmHg)

< 140

TDD (mmHg)

< 90

GD pre-prandial
kapiler

80-130 **

GD 2 jam PP kapiler

< 180 **

A1c (%)

< 7 (atau individual)

Kolesterol LDL
(mg/dl)

< 100 (< 70 bila risiko KV sangat

tinggi)

Kolesterol HDL
(mg/dl)

Pria > 40, wanita > 50

Trigliserida (mg/dl)

< 150

*The Asia Pacific Redefining Obesity and Its Treatment 2000

** Standards of Medical Care in Diabetes, ADA 2015

Drugs Mode of Action

GI

Insulin Secretion

DPP-4 I
GLP-1 RA
Glucosidase
Inhibitors
Amylin
Bile acid
sequestrant

Sulfonyureas
Meglitinides
DPP-4 I
GLP-1 RA

Glucagon Secretion
DPP-4 I
GLP-1 RA
Amylin

Appetite Control
DPP-4 I
GLP-1 RA
Amylin

Hepatic Glucose
Output

Glucose
Reabsorption

Metformin
Thiazolidinediones

SGLT2 Inhibitors

Lipotoxicity

Thiazolidinediones

Glucose Uptake and

Utilization
Thiazolidinediones
Metformin

Ralph. A DeFronzo Banting Lecture Diabetes 2009; 58:773-95

Risk & Benefit Characteristic of Glucose Lowering

Agents

Class

Advantages

Disadvantages

Biguanide Extensive experience, no

s
hypoglycaemia, CVD
events (UKPDS)

GIT side effects, lactic

acidosis risk (rare),
Vitamin B12 def, multiple
contraindications: CKD,
acidosis, hypoxia,
dehydration, etc

SUs

Hypoglycaemia, weight
gain, low durability

Extensive experience,
microvascular risk
(UKPDS)

Meglitinid Postprandial glucose

es
excursions, dosing
(glinide) flexibility

Hypoglycaemia, weight
gain, frequent dosing
schedule

TZDs

Weight gain, oedema /

heart failure, bone
fractures

No hypoglycaemia,
Durability, HDL-C,
triacylglycerols
ADA Standards of Medical
Care 2015
(pioglitazone)

Risk & Benefit Characteristic of Glucose Lowering

Agents

Class

Advantages

Disadvantages

Glucosidase
inhibitors

No hypoglycaemia, nonsystemic

GIT side effects, frequent

dosing schedule

DPP-4
inhibitors

No hypoglycaemia

Angioedema/urticaria and
other immune-mediated
dermatological effects

Insulins

Universally effective,
theoretically unlimited
efficacy, microvascular
risk (UKPDS)

Hypoglycaemia, weight
gain, injectable, training
requirements, Stigma
(for patients)

GLP-1
receptor
agonists

No hypoglycaemia, weight
reduction

GIT side effects, C cell

hyperplasia/ medullary
thyroid tumours in
animals, injectable,
training requirements

ADA Standards of Medical Care 2015

Risk & Benefit Characteristic of Glucose

Lowering Agents
Dopamine-2
Agonists
(bromocriptine)

No hypoglycaemia

Dizziness/syncope,
nausea, fatigue,
rhinitis

SGLT2 inhibitors
(dapaglifozin)

No hypoglycemia,
Weight, Blood
pressure, Effective
at all stages of T2DM

Genitourinary
infections, LDL-C,
Polyuria, Volume
depletion/hypotensio
n/
dizziness

Bile acid
sequestrants

No hypoglycemia,
LDL-C

Constipation,
Triglycerides, May
absorption of other
medications

ADA Standards of Medical Care 2015

Not available in Indonesia

Insulin Remains The Most Effective Glucose Lowering

Agent
Decrease in HbA1c: Potency of monotherapy
0.0
HbA1c%

-0.5
-1.0
-1.5

Insulin

Metformin

TZD

Exenatide

Pramlintide

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

GLP-1

DPPIV inh

AGIs

-2.5

SU/GLIN

-2.0

CHOOSING INSULIN EARLIER

FOR BETTER EFFICACY

Why T2DM Need Insulin?

HOMA: homeostasis model assessment

Lebovitz. Diabetes Reviews 1999;7:13953 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:124958)

Insulin requirement in diabetic patient

Basal insulin requirement:

Amount of exogenous insulin per unit of time necessary toprevent unchecked gluconeogenesis and ketogenesis
Prandial Insulin:
The nutritional insulin requirement is for the prandial requirement
Stress-related insulin
Acute illness or stressors, or other diabetogenic drugs

24

Pharmacokinetic of Several Insulin Preparations

Aspart, glulisine, lispro (4-6jam)
Reguler (6-8 jam)
NPH (12-20 jam)

Kadar Insulin Plasma

Ultralente (18-24 jam)

Detemir, Glargine (24 jam)

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

jam
Petunjuk praktis perkeni 2011

Conclusion

Indonesia is moving from 7th to 5th of the largest diabetes population in the
world within 1 year

It is important to reach good glycemic control

The benefit of good glycemic control are reductions in microvascular &

macrovascular complications and in the overall cost for the society for
treating diabetes

Insulin remains the most efficacious glucose lowering agent than oral
hypoglycaemic agent and most diabetes patients will need insulin over time.

Insulin therapy is an ongoing process

Secondary failure with

OAD
Initiating insulin
therapy
Titration of insulin
doses to target
Intensification of the insulin
regimens if target is not
achieved

tq