insulin initiation : when we should start with basal insulin?
TRANSCRIPT
Insulin Initiation : When We should Start with Basal Insulin?
Dr. Agus Taolin , SpPD, FINASIMPAPDI CABANG BOGOR
PIT IDI Bogor10 November 2013
20102000171 million1
2030552 million2
2011366 million2
Diabetes is a global diseaseEstimated global prevalence of diabetes
1. Wild. Diabetes Care. 2004. 27:1047-1053.2. International Diabetes Federation. IDF Diabetes Atlas. Fifth Edition. 2011
DM PREVALENCE BY PROVINCES IN INDONESIA
Laurentia Litbangkes 2008
Diabetes in Indonesia
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. Fonseca VA. Br J Diab Vasc Dis 2008;8:S3 2. Nathan DM, et al. Diabetes Care 2009;32:193-203
Loss of beta cell Pancreas
Loss beta cell
Glucotoxicity
Oxidative stress
Apoptosis by:
Sulfonylureas
Glucocorticoids
Apoptosis induced by
leptin,
Autoimmune
responses
Proinflammatory
cytokines
Lipotoxicity: FFA,
LDL-C and low HDL-C
Wajchenberg BL. Et al.. Endocr. Rev. 28, 187-218 (2007)
1. Adapted from: Ramlo-Halsted BA, Edelman SV. Clincial Diabetes 2000;18(2): http://journal.diabetes.org/clinicaldiabetes/v18n22000/pg80.htm
T2DM: Progressive loss of insulin secretion with increasing insulin resistance1
Impairedglucose tolerance
Undiagnoseddiabetes
Insulin resistance
Known diabetes
Insulin secretion Postprandial glucose
Fasting glucose
Microvascular complicationsMacrovascular complications
Modalities in Diabetes Management
Diet Management
Physical Activity
EducationAnd orInsulin
Injection
Oral Anti Diabetic
ADA Consensus statement,2010
Diabetic Patients
Slide no 11New position statement of the ADA and EASD on management of hyperglycemia in type 2 diabetes
Inzucci SE, et al. Diabetologia. 2012
Basal I nsulin
Algoritme Pengelolaan DM Tipe 2 Tanpa Disertai Dekompensasi
DM Tahap I Tahap II Tahap III
GHS GHS+
Monoterapi
GHS+
Kombinasi 2 OHOGHS
+Kombinasi 2 OHO
+Basal Insulin
GHS+
Kombinasi 3 OHO
Jalur alternatif jika tidak terdapat insulin,
menolak dan target glukosa belum optimal
Insulin Intensif
Catatan1. Dinyatakan gagal
bila dengan terapi 2-3 bulan tidak mencapai target HbA1c <7%
2. Bila tidak ada pemeriksaan HbA1c dapat digunakan pemeriksaan glukosa darah. Rata-rata glukosa darah sehari dikonversikan ke HbA1c menurut kriteria ADA 2010
Konsensus Pengelolaan dan pencegahan Diabetus Melitus, PB Perkeni, 201112
Evolving Treatment Paradigm in T2DM : Delayed Insulin Therapy
Type 2 Diabetes Pre-diabetesDiet management + exercise
Oral monotherapy
Oral combination
GLP-1 Analogues and DPP-IV inhibitor
Insulin Amylin ( pramlintide )
- 10 -5 0 +5 +10 +15 Years from Diagnosis
Joslin Diabetes Centre
13
Delayed to intensive therapy Study to evaluation how many patients move tonext 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
• 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.
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
Stepwise Intensification of Insulin Therapy
Progressive deterioration of -cell function
Lifestyle changes
Oral agents
BasalAdd basal insulin and titrate
Basal plusAdd prandial insulin at main
meal
Basal bolusAdditional prandial doses as neededFBG above target
HbA1c above target
HbA1c above target
FBG at targetHbA1c above target
Adapted from Raccah D et al. Diabetes Metab Res Rev 2007;23(4):257-64.
Insulin • A hormone secreted by the beta cells • Secreted in response to glucose or other stimuli,
such as amino acids• Normal response characterized by low basal levels of
insulin, with surges of insulin triggered by a rise in blood glucose
Insu
lin
60
02040
Breakfast Lunch Supper
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
Levemir NovoRapid
Insulin endogen
--------
NovoMix
Breakfast Lunch Dinner Bed time
Physiologic insulin secretionAnalogue insulin mechanisme of action
Jenis-jenis insulin
0 1 2 53 4 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Kad
arinsu
lin p
lasm
a
Reguler (6–8 jam)NPH (12–20 jam)
Ultralente (18–24 jam)
Jam
Glargine (20-24 jam)
Aspart, glulisine, lispro (4–6 jam)
Detemir
Hirsh IB, N Eng J Med 2005;352:174-183
Insulin types and actionOnset (hrs) Peak (hrs) Duration (hrs)
Rapid Acting analoglispro aspartglulisine
<¼ ¾-2½ 3½-4½
Short acting (Human)Regular (soluble) ½-1 2-4 6-8Intermediate acting NPH 1-2 6-12 18-24 Long acting(analog)glarginedetemir
3-41-2
3-243-8
≥2412-24
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
Insulin remains the most efficacious glucose lowering agent
Decrease in HbA1c: Potency of monotherapy
HbA
1c %
Nathan et al., Diabetes Care 2009;32:193-203.
CHOOSING INSULIN EARLIERFOR BETTER EFFICACY
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
What is the optimal target HbA1c level?
• Goals of optimum HbA1c levels:• Good glycaemic control• Minimise development and progression of microvascular
and macrovascular complications
HbA1c<7.0%
HbA1c<7.0%
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
HbA1c<7.0%EMA3
EASD/ADA1
IDF2
Treat T2DM early for long-term benefits1
• Long-term benefits in reducing cardiovascular risk can be achieved with good control from diagnosis1
-14%
-37%
-21%
Myocardial infarction
Microvascular complications
Death related to diabetes
Each HbA1cpercentage
pointreductioncounts3
HbA1c
-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
50% of patients with T2DM with complications already have them at diagnosis2
New ADA/EASD Position on Sequential Insulin Strategy in Type 2 Diabetes
Non-Insulin Regimes
Basal Insulin OnlyUsually with OAD
Basal Insulin + 1 mealtime rapid-acting injection Pre-mixed Insulin twice-daily
Basal Insulin + ≥ 2 mealtime rapid-acting injection
1
2
+3
Low
Mod.
High
Number of Injections
Regimen Complexity
FlexibilityLess FlexibleMore Flexible
Convenience*More ConvenientLess Convenient
Inzucci SE, et al. Diabetologia. 2012. * Gumprecht et al. Intensification to to biphasic insulin aspart 30/70. Int J Clin Pract 2009
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 + 3 OAD
INITIATE INSULIN
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
Simple Dose titration with Levemir
Patients who experienced hypoglycemia reduced their daily dose by 3 units
FPG target range70-90 mg/dL
FPG <70 mg/dL (3.8 mmol/L)
FPG>90 mg/dl (5.0 mm/L)
Mean 3-day FPG (mg/dL)
Maintaindose
units
FPG target range80-110 mg/dL
FPG <80 mg/dL (4.4 mmol/L)
FPG>110 mg/dL (6.1 mmol/L)
Blonde L et al. Diabetes Obes Metab. 2009; 11(6):623-631.
Increase3 units
Decrease3 units
Levemir® Dose Titration Guidelines: 3-0-3 AlgorithmStart with Levemir 10 U or 0,1-0,2 U per Kg BB
Levemir®/Glargine Head-to-Head:Similar Profiles in Type 2 Diabetes
Time (h)Klein O et al. Diab Obes Metab 2007; 9:290-299
Gluc
ose
infu
sion
rate
(m
g/kg
/min
)
0 2 4 6 8 10 12 14 16 18 20 22 240
0.5
1.0
1.5
2.0
2.5
3.0
0.4 U/kg 0.8 U/kgInsulin detemir
Insulin glargine
Levemir reduces nocturnal hypoglycaemia by up to 65% compared to NPH
Phillis-Tsimikas. Clin Ther 2006;28(10):1569–81; Riddle et al 2003. Diabetes Care; 26 (11): 3080-6; Asakura T et al, 2008. Expert Opin Pharmacother; 10 (9): 1-5; Hanel H et al 2008. J Diabetes Sci Technol; 2 (3): 478-81
Insulin NPHInsulin Determir
Insulin glargine
Rela
tive
Risk
Riddle et al., 2003 Phillis-Tsimikas et al., 2006
-29% -44% -53% -65%
NPH vs. glargine NPH vs. detemir
• Observational study of people with T2DM in routine clinical practice
• Study objectives• Primary: number of attributed adverse drug
reactions (includes major hypoglycaemia)• Secondary: other safety and effectiveness
measures
BASELINEWeek 0
INTERIMWeek 12
FINALWeek 24
Start a study insulin• Biphasic insulin aspart 30
• Insulin detemir• Insulin aspart
A1chieve study overview and design
HbA1c (%) FPG (mg/dl) PPG (mg/dl)Baseline values 9.5 219 263
n 147 317 295
Levemir ± OAD: Indonesia efficacy results
Insulin naïve
*p<0.001
Levemir ± OAD: Indonesia hypoglycaemia results
5,10
0,30
4,80
0,00 0,00 0,000,0
1,0
2,0
3,0
4,0
5,0
6,0
Overall Major NocturnalInsulin naïve Insulin naïve Insulin naïve
No. of pt w/hypo 19 0 1 0 18 0
Perc
ent w
ith a
t lea
st o
ne e
vent
Baseline 24 weeks
A1chieve: Self-rated health in insulin naive patients (Levemir)
24 weeksBaseline
Best imaginablehealth
Worst imaginable
health
Patients on Levemir®
0102030405060708090
100
Baseline 24 weeks
Slide no 39
SURVEI 30 peserta simposium IDI Bogor 2013
Tgl.9 nov 2013
Slide 40
Apakah dokter tahu tentang Insulin Basal dan Prandial
Slide 41
Apakah dokter menggunakan Insulin pada pasien
Rawat Jalan
Slide 42
Apaka dokter pernah menggunakan Insulin basal
(mis.levemir) pada Pasien Diabetes
Slide 43
Apakah dokter Pernah menggunakan Insulin Prandial (misalnya Novorapid)
Slide 44
Apakah dokter tahu tentang Insulin Basal dan Prandial
Slide 45
Apakah dokter menggunakan Insulin saja atau Kombinasi dengan diabetes
oral
Slide 46
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.
Slide 48
Thank You