Insulin Initiation : When We
should Start with Basal
Insulin?

Dr. Agus Taolin , SpPD, FINASIM
PAPDI CABANG BOGOR
PIT IDI ...
Diabetes is a global disease

Estimated global prevalence of diabetes

171 million1
2000
1.
2.

366 million2
2011
2010

Wi...
DM PREVALENCE BY PROVINCES IN INDONESIA
Diabetes in Indonesia

Laurentia Litbangkes 2008
Diabetes is a progressive disease
• Type 2 diabetes (T2DM) progression is characterised by decline in beta-cell function a...
7

papdi.bogor@ya
hoo.com

Loss of beta cell Pancreas
Apoptosis
induced by
leptin,

Autoimmu
ne
responses

Apoptosis
by:
S...
8

papdi.bogor@ya
hoo.com

Progressive Loss of β-cell Function
in T2DM
T2DM: Progressive loss of insulin
secretion with increasing insulin resistance1
Impaired
glucose tolerance

Undiagnosed
di...
10

papdi.bogor@ya
hoo.com

Modalities in Diabetes Management
Diet
Management

Physical
Activity

Oral Anti Diabetic

Diab...
New position statement of the ADA and EASD on
management of hyperglycemia in type 2 diabetes

Basal
Insulin

Inzucci SE, e...
Algoritme Pengelolaan DM Tipe 2 Tanpa Disertai Dekompensasi
DM

Tahap I

GHS

GHS
+
Monoterapi

Catatan
1. Dinyatakan gaga...
Evolving Treatment Paradigm
in T2DM : Delayed Insulin Therapy
- 10

Years
from
Diagnosis

0

-5

+5

+10

13

+15
Amylin (...
14

papdi.bogor@ya
hoo.com

Study to evaluation how many patients move to
next step of therapy when A1c > 8 %
• Sulfonilur...
15

papdi.bogor@ya
hoo.com

• Most patients with type 2 diabetes
require insulin therapy when OAD provide
suboptimal glyce...
16

papdi.bogor@ya
hoo.com

Intensive diabetes Management
•
•
•
•
•

Mode of treatment for person with Diabetes
Goal : Eug...
17

papdi.bogor@ya
hoo.com

Stepwise Intensification of Insulin Therapy

FBG at target
HbA1c above target
FBG above target...
18

Insulin

papdi.bogor@ya
hoo.com

• A hormone secreted by the beta cells

• Secreted in response to glucose or other st...
19

papdi.bogor@ya
hoo.com

Basal and Prandial Insulin

•Basal insulin

replacement mimics the constant
physiologic releas...
Physiologic insulin secretion

Analogue insulin mechanisme of action

-------

Breakfast

Lunch

Dinner

Insulin endogen
L...
21

Jenis-jenis insulin

papdi.bogor@ya
hoo.com

Aspart, glulisine, lispro (4–6 jam)

Kadar insulin plasma

Reguler (6–8 j...
papdi.bogor@ya
hoo.com

Insulin types and action
Onset (hrs)

Peak (hrs)

Duration (hrs)

Rapid Acting analog
lispro
aspar...
23

Insulin therapy
• Insulin therapy aims to replicate the normal
physiological insulin response
• Insulin regimens shoul...
Insulin remains the most efficacious glucose
lowering agent

HbA1c %

Decrease in HbA1c: Potency of monotherapy

CHOOSING ...
25

papdi.bogor@ya
hoo.com

Goal Insulin Therapy
• Administration of exogenous insulin to approximate the
normal physiolog...
What is the optimal target HbA1c level?
EASD/ADA1

HbA1c
<7.0%

IDF2

HbA1c
<7.0%

EMA3

HbA1c
<7.0%

• Goals of optimum H...
Treat T2DM early for long-term benefits1
• Long-term benefits in reducing cardiovascular risk can be achieved with
good co...
New ADA/EASD Position on Sequential Insulin
Strategy in Type 2 Diabetes
Non-Insulin
Regimes

Number of
Injections

Regimen...
Insulin can be initiated at any time
•

Traditionally, insulin has been reserved as the last line of therapy…

•

…However...
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...
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 w...
Levemir®/Glargine Head-to-Head:
Similar Profiles in Type 2 Diabetes
Insulin detemir

2.5
(mg/kg/min)

Glucose infusion rat...
Levemir reduces nocturnal hypoglycaemia by up to
65% compared to NPH
NPH vs. glargine
-44%

-53%

-65%

Relative Risk

-29...
A1chieve study overview and design
• Observational study of people with T2DM in
routine clinical practice
Start a study
in...
Levemir ± OAD:
Indonesia efficacy results
HbA1c (%)

Insulin naïve
FPG (mg/dl)

PPG (mg/dl)

Baseline values

9.5

219

26...
Levemir ± OAD:
Indonesia hypoglycaemia results
Overall

Major

Insulin naïve
No. of pt w/hypo

19

Nocturnal

Insulin naïv...
A1chieve: Self-rated health in insulin naive
patients (Levemir)
Patients on
Best imaginable Levemir®
health
100
90
80
70
6...
Slide no 39
Slide 40

SURVEI
30 peserta simposium IDI Bogor 2013
Tgl.9 nov 2013
Slide 41

Apakah dokter tahu
tentang Insulin Basal dan Prandial
Slide 42

Apakah dokter menggunakan Insulin
pada pasien Rawat Jalan
Slide 43

Apaka dokter pernah
menggunakan Insulin basal
(mis.levemir) pada Pasien Diabetes
Slide 44

Apakah dokter Pernah menggunakan
Insulin Prandial (misalnya Novorapid)
Slide 45

Apakah dokter tahu
tentang Insulin Basal dan Prandial
Slide 46

Apakah dokter menggunakan Insulin
saja atau Kombinasi dengan diabetes
oral
Conclusion
• Diabetes is a progressive disease that is increasing in prevalence in the world
• Starting with basal insulin...
Slide 48

Thank You
Insulin Initiation : When We should Start with Basal Insulin?
Insulin Initiation : When We should Start with Basal Insulin?
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Insulin Initiation : When We should Start with Basal Insulin?

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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

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  • 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 &lt; 0.0001), 21% for deaths related to diabetes (15% to 27%, P &lt; 0.0001), 14% for myocardial infarction (8% to 21%, P &lt; 0.0001), and 37% for microvascular complications (33% to 41%, P &lt; 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%
  • Insulin Initiation : When We should Start with Basal Insulin?

    1. 1. Insulin Initiation : When We should Start with Basal Insulin? Dr. Agus Taolin , SpPD, FINASIM PAPDI CABANG BOGOR PIT IDI Bogor 10 November 2013
    2. 2. Diabetes is a global disease Estimated global prevalence of diabetes 171 million1 2000 1. 2. 366 million2 2011 2010 Wild. Diabetes Care. 2004. 27:1047-1053. International Diabetes Federation. IDF Diabetes Atlas. Fifth Edition. 2011 552 million2 2030
    3. 3. DM PREVALENCE BY PROVINCES IN INDONESIA
    4. 4. Diabetes in Indonesia Laurentia Litbangkes 2008
    5. 5. 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
    6. 6. 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)
    7. 7. 8 papdi.bogor@ya hoo.com Progressive Loss of β-cell Function in T2DM
    8. 8. 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
    9. 9. 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
    10. 10. 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
    11. 11. 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
    12. 12. 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
    13. 13. 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
    14. 14. 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.
    15. 15. 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
    16. 16. 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.
    17. 17. 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
    18. 18. 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
    19. 19. Physiologic insulin secretion Analogue insulin mechanisme of action ------- Breakfast Lunch Dinner Insulin endogen Levemir NovoRapid NovoMix Bed time
    20. 20. 21 Jenis-jenis insulin papdi.bogor@ya hoo.com Aspart, glulisine, lispro (4–6 jam) Kadar insulin plasma Reguler (6–8 jam) NPH (12–20 jam) Ultralente (18–24 jam) Glargine (20-24 jam) Detemir 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 Hirsh IB, N Eng J Med 2005;352:174-183
    21. 21. papdi.bogor@ya hoo.com Insulin types and action Onset (hrs) Peak (hrs) Duration (hrs) Rapid Acting analog lispro aspart glulisine <¼ ¾-2½ 3½-4½ ½-1 2-4 6-8 1-2 6-12 18-24 Short acting (Human) Regular (soluble) Intermediate acting NPH Long acting(analog) glargine detemir 3-4 1-2 3-24 3-8 ≥24 12-24
    22. 22. 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
    23. 23. 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.
    24. 24. 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
    25. 25. 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
    26. 26. 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
    27. 27. 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*
    28. 28. 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
    29. 29. 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
    30. 30. 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.
    31. 31. 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
    32. 32. 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
    33. 33. 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
    34. 34. Levemir ± OAD: Indonesia efficacy results HbA1c (%) Insulin naïve FPG (mg/dl) PPG (mg/dl) Baseline values 9.5 219 263 n 147 317 295 -80 Change from baseline to week 24 0.0 -1.0 -100 -101* -2.0 -2.2* -115* -3.0 -120 *p<0.001
    35. 35. Levemir ± OAD: Indonesia hypoglycaemia results Overall Major Insulin naïve No. of pt w/hypo 19 Nocturnal Insulin naïve 0 1 Insulin naïve 0 18 0 Percent with at least one event 6,0 5,0 5,10 4,80 4,0 3,0 2,0 1,0 0,0 0,00 0,30 0,00 0,00 Baseline 24 weeks
    36. 36. A1chieve: Self-rated health in insulin naive patients (Levemir) Patients on Best imaginable Levemir® health 100 90 80 70 60 50 40 24 weeks Baseline 30 20 Worst imaginable health 10 0 Baseline 24 weeks
    37. 37. Slide no 39
    38. 38. Slide 40 SURVEI 30 peserta simposium IDI Bogor 2013 Tgl.9 nov 2013
    39. 39. Slide 41 Apakah dokter tahu tentang Insulin Basal dan Prandial
    40. 40. Slide 42 Apakah dokter menggunakan Insulin pada pasien Rawat Jalan
    41. 41. Slide 43 Apaka dokter pernah menggunakan Insulin basal (mis.levemir) pada Pasien Diabetes
    42. 42. Slide 44 Apakah dokter Pernah menggunakan Insulin Prandial (misalnya Novorapid)
    43. 43. Slide 45 Apakah dokter tahu tentang Insulin Basal dan Prandial
    44. 44. Slide 46 Apakah dokter menggunakan Insulin saja atau Kombinasi dengan diabetes oral
    45. 45. 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.
    46. 46. Slide 48 Thank You
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