PIN PAPDI XIII

Palembang 2015

Benny Santosa
Diabetes is a global disease
Estimated global prevalence of diabetes

171 million1 366 million2 552 million2

2000 2011
2010 2030

1. Wild. Diabetes Care. 2004. 27:1047-1053.

2. International Diabetes Federation. IDF Diabetes Atlas. Fifth Edition. 2011
 Impaired Undiagnosed Known
glucose tolerance diabetes diabetes

Insulin resistance

Insulin secretion
Postprandial glucose

Fasting glucose

Microvascular complications
Macrovascular complicationsations

1. Adapted from: Ramlo-Halsted BA, Edelman SV. Clincial Diabetes 2000;18(2): http://journal.diabetes.org/clinicaldiabetes/v18n22000/pg80.htm
Type 2 diabetes (T2DM) progression is characterised by decline in beta-cell
function and worsening insulin resistance1
Getting to, or maintaining, target HbA1c levels in T2DM requires intensified
treatment over time2

1. Fonseca VA. Br J Diab Vasc Dis 2008;8:S3

2. Nathan DM, et al. Diabetes Care 2009;32:193-203
Insulin
Inzucci SE, et al. Diabetologia. 2012
 KADAR HbA1c
<7% 7-8% 8-9% >9% 9-10% >10%

GHS GHS

Gaya Hidup
+
Sehat Monoterapi GHS

•Penurunan Met, SU, +

berat badan AGI, Glinid, Kombinasi GHS
•Mengatur diit
•Latihan TZD, DPP-IV 2 obat +
Jasmani teratur Met, SU, Kombinasi GHS
AGI, Glinid, 3 obat +
Catatan TZD, DPP-IV Met, SU, Kombinasi
1.Dinyatakan gagal bila dengan
terapi 2-3 bulan tidak mencapai AGI, Glinid, 2 obat
target HbA1c <7% TZD, DPP-IV Met, SU,
2.Bila tidak ada pemeriksaan
HbA1c dapat digunakan AGI, Glinid,
pemeriksaan glukosa darah. Rata- TZD
rata glukosa darah sehari
dikonversikan ke HbA1c menurut + GHS
kriteria ADA 2010
Basal Insulin +
Insulin
*insulin intensif : penggunaan insulin basal bersamaan dengan insulin prandial Intensif*
Konsensus Perkeni 2011
 Non-Insulin Regimes Number of Regimen
Injections Complexity

Basal Insulin Only

Usually with OAD 1 Low

Basal Insulin + 1 mealtime rapid-

acting injection
mixed Insulin twice-daily 2 Mod.

Basal Insulin + ≥ 2 mealtime rapid-

+3 High
acting 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
 HbA1c
EASD/ADA1
<7.0%

HbA1c
IDF2
<7.0%

HbA1c
EMA3
<7.0%

Goals of optimum HbA1c levels:

 Good glycaemic control
 Minimise development and progression of microvascular
and macrovascular complications

1. Inzucchi et al. Diabetes care. Published online 19Apr2012.

2. IDF Treatment Algorithm. International Diabetes Federation 2011. http://www.idf.org/treatment-algorithm-people-type-2-diabetes
3. EMA Draft guidance on clinical investigation in DM Jan 2010
Long-term benefits in reducing cardiovascular risk can be achieved
with good control from diagnosis1

50% of patients with T2DM with complications

already have them at diagnosis2

Myocardial infarction
-14%
Each HbA1c
percentage
point Microvascular complications
reduction -37%
counts3
Death related to diabetes
HbA1c -21%

-1%

1. Holman, et al. NEJM 2008;359:1577–89

2. UKPDS 6. Diabetes Res 1990;13(1):1-11
3. Stratton, et al. BMJ 2000;321(7258):405-12
 Decrease in HbA1c: Potency of monotherapy
HbA1c %

CHOOSING INSULIN EARLIER

FOR BETTER EFFICACY

Nathan et al., Diabetes Care 2009;32:193-203.

 Over time,
most patients need insulin to achieve glycemic
control
• Traditionally, insulin has been reserved as the last line of therapy…
• …However, considering the benefits of normal glycemic status, Insulin
can be initiated earlier and as soon as possible

Inadequate
+ 1 OAD + 2 OAD + 3 OAD
Lifestyle

INITIATE INSULIN
 I don’t want it.!

It hurts ! Expensive !

Severe!

Drug Hypoglycemia !
addiction ?
“Fix the Fasting First”
Start with basal insulin
Ideal Basal Insulin

• Closely mimic normal pancreatic basal insulin secretion

• No distinct peak effect
• Continued effect over 24 hours
• Reduce nocturnal hypoglycemia
• Once-daily administration for patient compliance
• Predictable absorption pattern
To normalise HbA1c, both FPG and PPG must be
reduced

100

30%
% contribution to HbA1c

80 45% 40% PPG

50%
70%
60 FPG

40
70%
55% 60%
50%
20
30%

0
<7.3 7.3–8.4 8.5–9.2 9.3–10.2 >10.2
HbA1c range (%)

Adapted from Monnier et al. Diabetes Care 2003;26:881–5.

 400
20

Plasma glucose (mmol/l)

Plasma glucose (mg/dl)

300 T2DM
15

200 Hyperglycaemia due to an increase in fasting glucose

10

100
5
Normal
Meal Meal Meal
0 0
6 10 14 18 22 2 6
Time of day (hours)

Comparison of 24-hour glucose levels in control subjects vs patients with diabetes (p<0.001).
Adapted from Polonsky K, et al. N Engl J Med 1988;318:1231―9.
 Prandial/Bolus/mealtime insulin
50
Insulin
(µU/mL) 25
Basal Insulin
0
Breakfast Lunch Dinner

Post Prandial Glucose

150
Glucose
(mg/dL) 100
50 Basal Glucose

0 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9
AM PM

Time of day
 Basal Insulin
will cover fasting blood glucose &
between meals

• Human Insulin:
Humulin N, Insulatard HM
• Analog Insulin:
Insulin Glargine (Lantus),
Insulin Detemir (Levemir)
 Long Acting Insulin Analog

Insulin Glargine
(Lantus)
 Peakless
 Clear solution
 Basal Insulin
 Could be given 1 – 2
times a day
 Not for intravenous
use
The INSIGHT Study
INSIGHT, Implementing New Strategies with Insulin Glargine for Hyperglycemia Therapy

 405 insulin-naïve patients with type 2 diabetes

 Randomized to early insulin glargine or optimization
of existing OADs
 Patients self-titrated their bedtime insulin
glargine by 1 U per day to target FPG < 5.6
mmol/L (< 100 mg/dL)

HbA1c ≤ 6.5% in 20% of patients

HbA1c ≤ 7.0% in 50% of patients

Gerstein H et al. Diabetic Med 2006;23:736–42

 9.5 Baseline Study endpoint (after insulin glargine treatment)
9.13
9.0 8.85 8.8 8.8
8.71
HbA1c changes (%)

8.61
8.5

8.0

7.5
7.14 7.15 7.14
6.96 6.96
7.0 6.8

6.5

6.0

TTT1 LANMET2 APOLLO3 4

LAPTOPTriple Therapy5 INITIATE6

1. Riddle M, et al. Diabetes Care 2003;26:3080–6. 2. Yki-Järvinen H, et al. Diabetes Care 2006;49:442–51.
3. Bretzel RG, et al. Lancet 2008;371:1073−84. 4. Janka H, et al. Diabetes Care 2005;28:254−9.
5. Rosenstock J, et al. Diabetes Care 2006;29:554–9. 6. Yki-Järvinen H, et al. Diabetes Care 2007;30:1364–69.
 Start at clinic, do not need to hospitalized patients to
start insulin
 Empowering the patient:
 Consultation before starting insulin
 Teach SMBG
 Motivate the patient
Consultation at start of insulin therapy
Demonstrate insulin injection technique
Provide instructions for insulin dose adjustment
Explain symptoms and management of hypoglycaemia

 Indepth diabetes education with diabetes educator

 Initiate insulin with a single injection of a basal insulin

• Bedtime or morning long-acting insulin OR

• Bedtime intermediate-acting insulin
INITIATE
• Daily dose: 10 units or 0.2 units/kg

Check FBG
Daily
• Increase dose by 2 units every 3 days In the event of
hypoglycemia or FBG level <
until FBG is 3.89–7.22 mmol/L 3.89 mmol/L (< 70 mg/dL)
TITRATE (70–130 mg/dL) Reduce bedtime insulin
• If FBG is > 10 mmol/L (> 180 mg/dL), dose by ≥ 4 units, or by 10% if
increase dose by 4 units every 3 days > 60 units

Continue regimen and

MONITOR check HbA1c every 3 months

FBG, fasting blood glucose Adapted from Nathan DM, et al. Diabetologia 2006;49:1711–21
 OTHER CONSIDERATIONS
 Age
 Weight
 Sex / racial / ethnic / genetic differences
 Comorbidities
 Coronary artery disease
 Heart Failure
 Chronic kidney disease
 Liver dysfunction
 Hypoglycemia

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

• Diabetes mellitus is a chronic and progressive disease
with steadily worsening glycemia

• Shorten delays in treatment changes to achieve and

maintain normal glycemic goals

• A single daily injection of basal insulin glargine is a

simple and effective way to start insulin therapy

• Maintains targets with a low risk of hypoglycemia

• Always focused on patient-centered approach !