Insulin Initiation : When We should Start with Basal Insulin?
Dr. Agus Taolin , SpPD, FINASIM | PAPDI CABANG BOGOR
Disampaikan pada acara PIT VI IDI Kota Bogor | 9 Nopember 2013
6. Diabetes is a progressive disease
• 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.
2.
Fonseca VA. Br J Diab Vasc Dis 2008;8:S3
Nathan DM, et al. Diabetes Care 2009;32:193-203
7. 7
papdi.bogor@ya
hoo.com
Loss of beta cell Pancreas
Apoptosis
induced by
leptin,
Autoimmu
ne
responses
Apoptosis
by:
Sulfonylure
as
Glucocortic
oids
Glucotoxi
city
Oxidative
stress
Proinflam
matory
cytokines
Loss
beta
cell
Lipotoxicit
y: FFA,
LDL-C and
low HDL-C
Wajchenberg BL. Et al.. Endocr. Rev. 28, 187-218 (2007)
9. T2DM: Progressive loss of insulin
secretion with increasing insulin resistance1
Impaired
glucose tolerance
Undiagnosed
diabetes
Known
diabetes
Insulin resistance
Insulin secretion
Postprandial glucose
Fasting glucose
Microvascular complications
Macrovascular complications
1.
Adapted from: Ramlo-Halsted BA, Edelman SV. Clincial Diabetes 2000;18(2): http://journal.diabetes.org/clinicaldiabetes/v18n22000/pg80.htm
10. 10
papdi.bogor@ya
hoo.com
Modalities in Diabetes Management
Diet
Management
Physical
Activity
Oral Anti Diabetic
Diabetic
Patients
And or
Insulin
Injection
Education
ADA Consensus statement,2010
11. New position statement of the ADA and EASD on
management of hyperglycemia in type 2 diabetes
Basal
Insulin
Inzucci SE, et al. Diabetologia. 2012
Slide no 11
12. Algoritme Pengelolaan DM Tipe 2 Tanpa Disertai Dekompensasi
DM
Tahap I
GHS
GHS
+
Monoterapi
Catatan
1. Dinyatakan gagal
bila dengan
terapi 2-3 bulan
tidak mencapai
target HbA1c
<7%
2.
Bila tidak ada
pemeriksaan HbA1c
dapat digunakan
pemeriksaan
glukosa darah. Ratarata glukosa darah
sehari dikonversikan
ke HbA1c menurut
kriteria ADA 2010
Jalur alternatif
jika tidak
terdapat
insulin,
menolak dan
target glukosa
belum
optimal
Tahap II
GHS
+
Kombinasi 2 OHO
GHS
+
Kombinasi 2 OHO
+
Basal Insulin
GHS
+
Kombinasi
3 OHO
Tahap III
Insulin
Intensif
12
Konsensus Pengelolaan dan pencegahan Diabetus Melitus, PB Perkeni, 2011
13. Evolving Treatment Paradigm
in T2DM : Delayed Insulin Therapy
- 10
Years
from
Diagnosis
0
-5
+5
+10
13
+15
Amylin ( pramlintide )
Insulin
GLP-1 Analogues and
DPP-IV inhibitor
Oral combination
Oral
monotherapy
Diet management + exercise
Pre-diabetes
Type 2 Diabetes
Joslin Diabetes Centre
14. 14
papdi.bogor@ya
hoo.com
Study to evaluation how many patients move to
next step of therapy when A1c > 8 %
• Sulfonilurea ……..……… 35 % ad second drug
• Metformin ……………... 44 % ad other therapy
• 2 drugs OAD …………….. 18 % ( because the next step is
insulin )
• Spent 5 years duration before decided to give the next
therapy
Keiser Permante Group California
15. 15
papdi.bogor@ya
hoo.com
• Most patients with type 2 diabetes
require insulin therapy when OAD provide
suboptimal glycemic control
• Long-term glycemic improvement reduces the risks of
vascular complications.
• Different insulin regimens have varying effects on
glycemic control, weight gain, and the risk of
hypoglycemia
Holman RR, et al.N Engl J Med 2008;359:1577-89.
2. Turnbull FM, et al. Diabetologia 2009 August 5
3. Lasserson DS, et al. Diabetologiia, 2009;52:1990-2000.
16. 16
papdi.bogor@ya
hoo.com
Intensive diabetes Management
•
•
•
•
•
Mode of treatment for person with Diabetes
Goal : Euglycemic or near normal glycemic
Using all available resources to accomplish this goal
Prevent/ delayed loss beta cell pancreas
Prevent or delayed chronic complication of diabetes
ADA 2011
17. 17
papdi.bogor@ya
hoo.com
Stepwise Intensification of Insulin Therapy
FBG at target
HbA1c above target
FBG above target
HbA1c above target
Basal bolus
Additional prandial
doses as needed
Basal plus
Add prandial insulin at main
meal
HbA1c above
target
Basal
Add basal insulin and titrate
Oral agents
Lifestyle changes
Progressive deterioration of -cell function
Adapted from Raccah D et al. Diabetes Metab Res Rev 2007;23(4):257-64.
18. 18
Insulin
papdi.bogor@ya
hoo.com
• A hormone secreted by the beta cells
• Secreted in response to glucose or other stimuli,
such as amino acids
Insulin
• Normal response characterized by low basal levels of
insulin, with surges of insulin triggered by a rise in
blood glucose
60
40
20
0
Breakfast
Lunch
Supper
19. 19
papdi.bogor@ya
hoo.com
Basal and Prandial Insulin
•Basal insulin
replacement mimics the constant
physiologic release of insulin that regulates metabolism
and hepatic glucose production.
•Prandial insulin
replacement is intended to
mimic the postmeal insulin response to nutrient intake
23. 23
Insulin therapy
• Insulin therapy aims to replicate the normal
physiological insulin response
• Insulin regimens should be individualized
–
type of diabetes
–
willingness to inject
–
lifestyle
–
blood glucose monitoring
–
age
–
dexterity
–
glycaemic targets
papdi.bogor@ya
hoo.com
24. Insulin remains the most efficacious glucose
lowering agent
HbA1c %
Decrease in HbA1c: Potency of monotherapy
CHOOSING INSULIN EARLIER
FOR BETTER EFFICACY
Nathan et al., Diabetes Care 2009;32:193-203.
25. 25
papdi.bogor@ya
hoo.com
Goal Insulin Therapy
• Administration of exogenous insulin to approximate the
normal physiologic patterns of pancreatic insulin
secretion
• Reduce A1c, fasting, and postprandial plasma glucose
concentrations to recommended target level
26. What is the optimal target HbA1c level?
EASD/ADA1
HbA1c
<7.0%
IDF2
HbA1c
<7.0%
EMA3
HbA1c
<7.0%
• Goals of optimum HbA1c levels:
• Good glycaemic control
• Minimise development and progression of microvascular
and macrovascular complications
1.
2.
3.
Inzucchi et al. Diabetes care. Published online 19Apr2012.
IDF Treatment Algorithm. International Diabetes Federation 2011. http://www.idf.org/treatment-algorithm-people-type-2-diabetes
EMA Draft guidance on clinical investigation in DM Jan 2010
27. Treat T2DM early for long-term benefits1
• 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
Each HbA1c
percentage
point
reduction
counts3
HbA1c
-1%
1.
2.
3.
Holman, et al. NEJM 2008;359:1577–89
UKPDS 6. Diabetes Res 1990;13(1):1-11
Stratton, et al. BMJ 2000;321(7258):405-12
-14%
-37%
-21%
Myocardial infarction
Microvascular complications
Death related to diabetes
28. New ADA/EASD Position on Sequential Insulin
Strategy in Type 2 Diabetes
Non-Insulin
Regimes
Number of
Injections
Regimen
Complexity
Basal Insulin Only
Usually with OAD
1
Low
2
Mod.
+3
High
Basal Insulin + 1 mealtime
rapid-acting injection
Pre-mixed Insulin twice-daily
Basal Insulin + ≥ 2 mealtime
rapid-acting injection
More Flexible
Less Flexible
Less Convenient
More Convenient
Inzucci SE, et al. Diabetologia. 2012. * Gumprecht et al. Intensification to to biphasic insulin
aspart 30/70. Int J Clin Pract 2009
Flexibility
Convenience*
29. Insulin can be initiated at any time
•
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
Lifestyle
+ 1 OAD
+ 2 OAD
INITIATE INSULIN
+ 3 OAD
30. How to start Basal Insulin
• Start with basal insulin (Insulin Detemir) 10 U or 0,1-0,2 U per Kg BB
• Once daily injection, anytime injection but in same time per each day
31. Levemir® Dose Titration Guidelines:
3-0-3 Algorithm
Start with Levemir 10 U or 0,1-0,2 U per Kg BB
Simple Dose titration with Levemir
Mean 3-day FPG (mg/dL)
Increase
FPG>90 mg/dl (5.0 mm/L)
FPG target range
70-90 mg/dL
FPG <70 mg/dL (3.8 mmol/L)
3units
units
Maintain
dose
Decrease
3 units
FPG>110 mg/dL (6.1 mmol/L)
FPG target range
80-110 mg/dL
FPG <80 mg/dL (4.4 mmol/L)
Patients who experienced hypoglycemia reduced their daily dose by 3 units
Blonde L et al. Diabetes Obes Metab. 2009; 11(6):623-631.
32. Levemir®/Glargine Head-to-Head:
Similar Profiles in Type 2 Diabetes
Insulin detemir
2.5
(mg/kg/min)
Glucose infusion rate
3.0
0.4 U/kg
0.8 U/kg
Insulin glargine
2.0
1.5
1.0
0.5
0
0
2
4
6
8
10
12
14
16
18
Time (h)
Klein O et al. Diab Obes Metab 2007; 9:290-299
20
22
24
33.
34. Levemir reduces nocturnal hypoglycaemia by up to
65% compared to NPH
NPH vs. glargine
-44%
-53%
-65%
Relative Risk
-29%
NPH vs. detemir
Insulin Determir
Insulin NPH
Insulin glargine
Riddle et al., 2003
Phillis-Tsimikas et al., 2006
Phillis-Tsimikas. Clin Ther 2006;28(10):1569–81; Riddle et al 2003. Diabetes Care; 26 (11): 30806; Asakura T et al, 2008. Expert Opin Pharmacother; 10 (9): 1-5; Hanel H et al 2008. J Diabetes
35. A1chieve study overview and design
• Observational study of people with T2DM in
routine clinical practice
Start a study
insulin
• Biphasic insulin
aspart 30
• Insulin detemir
• Insulin aspart
BASELINE
Week 0
•
INTERIM
Week 12
FINAL
Week 24
Study objectives
•
Primary: number of attributed adverse drug
reactions (includes major hypoglycaemia)
•
Secondary: other safety and effectiveness
measures
47. Conclusion
• Diabetes is a progressive disease that is increasing in prevalence in the world
• Starting with basal insulin detemir is easy way to reach better glycemic control
• In Indonesia, in real life clinical practice (A1chieve study) Levemir show significant
improvements in overall glycaemic control in terms of HbA1c, FPG and PPG.
In the first edition of the IDF Diabetes Atlas, released in 2000, the estimated global diabetes prevalence was 151 million. In the newest 5th edition, the estimated diabetes prevalence for 2011 has risen to 366 million, representing 8.3% of the world’s adult population, with a prediction that by 2030 the number of people with diabetes will have risen to 552 million.
IDF juga memperkirakan bahwa 60% dari kasus diabetes tersebut ada di Asia.
-The prevalence of diabetes varies in different regions of Indonesia – it is higher in urban versus nonurban/outlying provinces and regions-According to the DiabCare Asia 2008 study, the prevalence of diabetes in Jakarta is 3.7%Riskedas 2007 (Cross sectional sampling for a registry conducted across Indonesia)Soewondo et al. DiabCare Asia 2008 Study. Med J Indones 2010.
Penelusuran Litbangkes menunjukkan bahwa prevalensi diabetes tertinggi di daerah di Indonesia adalah sebesar 11,1%, yaitu di Pontianak (Kalimantan Barat) dan Ternate (Maluku Utara).
On this slide we can see the usual pattern of insulin intensification in T2DM, moving from lifestyle interventions, the addition of OADs such as metformin, through to a regimen combining the OAD therapies with basal insulin, which has become a popular way to initiate insulin. When this combined BOT fails to control blood glucose levels, further intensification, to basal–bolus therapy, is recommended.
In the UKPDS study, the incidence of clinical complications was significantly associated with glycaemia3. Each 1% reduction in updated mean HbA1c was associated with reductions in risk of 21% for any end point related to diabetes (95% CI 17% to 24%, P < 0.0001), 21% for deaths related to diabetes (15% to 27%, P < 0.0001), 14% for myocardial infarction (8% to 21%, P < 0.0001), and 37% for microvascular complications (33% to 41%, P < 0.0001). No threshold of risk was observed for any end point.
Speaker Notes:[Click 1]: Detemir OD reduced the risk of hypoglycaemia by 53% versus NPH OD and reduced the risk of nocturnal hypoglycaemia by 65%