Beruflich Dokumente
Kultur Dokumente
in Type 2 DM:
Fccus on Insulin Glargine
Content
HbA1C
35.3 61.8 13.8 40.7 31.3 35.2 25.5 29.8
<7%
No
32.6 14.3 38.3 28.1 42.2 42.8 40.0 23.3
targets
1
38.7 37.1 40.6 36.6 39.2 37.9 43.6 37.5
target
2
23.4 36.3 19.2 29.8 16.2 15.2 12.7 29.8
targets
3
5.4 12.3 1.9 5.4 2.5 3.1 3.6 9.5
targets
HK, Hong Kong; JADE, Joint Asia Diabetes Evaluation; T2DM, type 2 diabetes mellitus So WY, et al. J Diabetes 2011;3:109–18.
Initiation of basal insulin is often delayed in Asia
• FINE Asia study1
– T2DM patients were poorly controlled, with a diabetes
duration of 9.3 years and an HbA1c level of 9.8% at basal
insulin initiation in the FINE Asia study
• CREDIT study2
– T2DM patients were also poorly controlled, with a
diabetes duration of 9 years and an HbA1c level of 9.2% at
insulin initiation in the CREDIT study
• International guidelines recommend considering
initiation of basal insulin soon after the failure of
monotherapy;3 despite this, evidence suggests that
insulin initiation in Asia is often delayed
80
40
20
24% 22% 21% 21% 20%
0
<8.0 8.0–<8.5 8.5–<9.0 9.0–<9.5 ≥9.5
Baseline HbA1c ranges
OAD, oral antidiabetic drug; T2DM, type 2 diabetes mellitus
*Pooled baseline data from six treat-to-target studies (n=1699 T2DM patients on diet ± OADs). Mean HbA1
8.69%, FPG 10.8 mmol/L (194 mg/dL). Calculations assume hyperglycemia is >5.6 mmol/L (100 mg/dL)
Riddle M, et al. Diabetes Care 2011; 34:2508–14.
Early intervention with basal insulin maintains glycemic
control in the long term
Clinical inertia
OAD OAD
OAD monotherapy OAD OAD
Diet
Intervention! + multiple daily
monotherapy uptitration combination + basal insulin insulin injections
Intervention!
10 Basal insulin
9 Intervention!
HbA1c (%)
Intervention!
8
Intervention!
OAD, oral antidiabetic drug; Del Prato S, et al. Int J Clin Pract 2005;59:1345–55.
ADA/EASD position statement 2015
Insulin glargine offers flexible dose adjustments to meet individual patients’ needs2,3
T2DM, type 2 diabetes mellitus 1. Sanofi. LANTUS® (Insulin Glargine) Prescribing Information. USA, 2015;
2. Strange P. J Diabetes Sci Technol 2007;1;540–8;
3. Barnett A. Clin Ther 2007;29:987–99.
Content
Glukosa Darah
A1c > 9 %
Stability
5
Porcellati INSIGHT Treat-to- APOLLO INITIATE CHO counting
target
12months 24 weeks 24 weeks 44 weeks 24 weeks 24 weeks
(n=60) (n=206) p=0.0007 vs (n=367) (n=174) (n=58) (n=273)
p<0.05 vs NPH conventional therapy NS vs NPH NS vs 3 lispro
Porcellati F, et al. Diabet Med 2004;21:1213–1220 APOLLO study. Bretzel RG. Diabetes 2006;55(Suppl 1): Abstract 326-OR
INSIGHT study. Gerstein H, et al. Diabet Med 2006;23(7):736–742. INITIATE study. Yki-Jarvinen H, Diabetes 2006;55(Suppl 1): Abstract 125-
Treat-to-target study. Riddle M, et al. Diabetes Care 2003;26:3080–3086 OR
CHO counting study. Bergenstal R, et al. Diabetes 2006;55(Suppl 1): 441-
Insulin detemir: HbA1c is < 7% in only one study
9
8.30 8.41
8.20
HbA1c (%)
Insulin Insulin
glargine detemir
Peakless, 24-hour profile enabling once-daily dosing
Low variability
Good glycaemic control with low incidence of hypoglycaemia ?
Easy titration to ambitious targets ?
Minimal weight change
Improved HRQoL and treatment satisfaction
Proven long-term safety
If not
controlled after
FBG target is reached
2 Add 1 rapid insulin injection Change to premix insulin
(or if dose >0.5 U/kg/day), treat PPG
before largest meal twice daily Mod
excursions with mealtime insulin
(Consider initial
• Start: 4 U/day or 0.1 U/kg, or 10% basal dose. If GLP-1-RA trial) • Start: Divide current basal dose into ⅔ AM, ⅓ PM
A1C <8%, consider bolus by same amount or ½ AM, ½ PM
• Adjust: dose by 1-2 U or 10-15% once-twice • Adjust: dose by 1-2 U or 10-15% once-twice
weekly until SMBG target reached weekly until SMBG target reached
• For hypoglycemia: Determine and address cause; • For hypoglycemia: Determine and address cause;
corresponding dose by 2-4 U or 10-20% corresponding dose by 2-4 U or 10-20%
If not If not
3+ controlled, consider Add ≥2 rapid insulin injections before meals controlled, consider High
basal-bolus (“basal-bolus”) basal-bolus
• Start: 4 U/day or 0.1 U/kg, or 10% basal dose/meal. If A1C <8%, consider bolus by same amount
• Adjust: dose by 1-2 U or 10-15% once-twice weekly until SMBG target reached
• For hypoglycemia: Determine and address cause; corresponding dose by 2-4 U or 10-20%
FPG, fasting plasma glucose; 1. Inzucchi SE, et al. Diabetes Care 2015;38:140–9;
FBG, fasting blood glucose 2. Handelsman Y, et al. Endo Pract 2015;21:1-87;
3. International Diabetes Federation. Global Guideline for Type 2 Diabetes. 2012;
Available at: http://www.idf.org/sites/default/files/IDF-Guideline-for-Type-2-Diabetes.pdf (accessed October 2015).
Simple up/down treat-to-target titration algorithms
with insulin glargine for individual dose adjustments
• Different titration algorithms based on FPG values have proven to be effective in
Studynumerous clinical studies
FPG (mmol/L) Dose titration Frequency of Down titration- dealing with
dose titration hypoglycemia
INSIGHT1 Until ≤5.5 Add 1 unit Daily Doses were reduced at the
discretion of the investigator in
response to biochemical or
clinical hypoglycaemia
LANMET2 • >10 • Add 4 units Every 3 days
• >5.5 • Add 2 units
FPG, fasting plasma glucose; INSIGHT, Implementing New Strategies with Insulin
Glargine for Hyperglycaemia Treatment; LANMET, Insulin glargine or NPH 1.Gerstein HC, et al. Diabetes Med 2006;23:736–42;
2. Yki-Järvinen H, et al. Diabetologia 2006;49:442–51;
combined with metformin in type 2 diabetes; TTT, Treat-to-Target Trial 3. Riddle MC, et al. Diabetes Care 2003;26:3080–6.
HbA1c goals are attained with insulin glargine using
simple titration algorithms
Mean HbA1c attained in various Treat-to-Target trials
Baseline Study end
9 8.7 8.8 8.7
8.6 8.6
7 6.8
5
1 2 3 4 5
Study name
Patient population
INSIGHT Observational
Study duration n=206… n=11,511…
Typically ~50% of patients attain HbA1c<7%1–5
APOLLO, Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on 1. Riddle MC, et al. Diabetes Care 2003;26:3080–6;
oral hypoglycaemic agents; INITIATE, Initiate Insulin by Aggressive Titration and Education; TTT, Treat-to-Target Trial; 2. Gerstein HC, et al. Diabetes Med 2006;23:736–42;
INSIGHT, Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment; Observational, Insulin 3. Bretzel RG, et al. Lancet 2008;371:1073–84;
glargine benefits patients with type 2 diabetes inadequately controlled on oral antidiabetic treatment. 4. Yki-Järvinen H, et al. Diabetes Care 2007;30:1364–9;
5. Schreiber SA & Haak T. Diabetes Obes Metab 2007;9:31–8.
Optimized titration can lead to
effective glycemic control
Once insulin is initiated, dose titration is important1,2
60
52 52
50
Percent of patients
40 34 35
30 Detemir
Glargine
20
10
0
A1c <7% A1c <7 % w/o hypo
Rosenstock J, et al. Diabetologia 2008;51(3):408–416
Efficacy Results
To reach efficacy to a similar level to once-daily Insulin Glargine, detemir requires
higher dose (77%) and often two injections
55%
Twice-daily
45%
Once-daily
*p<0.001; †p<0.012
At Night 5 4
Pts withdrawals due to adverse event N (%) 23 (7.9) 11 (3.85)
Injection site disorders
13 (13) 4 (5)
# of pts (# of events)
9%
30%
Glargine® Detemir®
n=5,683 N=694
P<0.05 P>0.05, NS
1. Currie CJ et al. Curr Med Res Opin 2007;23(Suppl 1): S33-S39
Insulin Detemir Dosing and Insulin Cost in
T2DM: Mean Daily Insulin Cost
Study
Study Design
N=12,537; 573 sites; 40 countries; Median (IQR) Follow-up: 6.2 y (5.8-6.6)
• Early addition of basal insulin glargine for > 6 yrs….
o is possible & feasible
o has a neutral effect on CVD, cancers, other outcomes
o reduces progression of diabetes
o modestly increases weight & hypoglycemia incidence
• Insulin glargine is now the best-studied of all glucose-lowering drugs
• No new side effects of basal insulin over 6-7 years
10
9.0
9 8.7 8.7 8.8
Mean HbA1c (%)
–1.4%
8 –1.6%
–1.7% –1.6%
7.6
7.1 7.2
7.0
7
50
44.6
Patients (%) achieving HbA1c
45
39.8
endpoint at 24 weeks
40 35.4 34
35
30 26.4
24.1 24.3
25
20 15.9
15
10
HbA1c HbA1c HbA1c HbA1c HbA1c HbA1c HbA1c HbA1c
5 <7% <7.5% <7% <7.5% <7% <7.5% <7% <7.5%
0
Gla + Met Gla + SU Gla + Met + SU Overall
(n=634) (n=906) (n=1,297) (n=2,837)
9.1 9.0
Mean HbA1c (%)
8.9
9.0 8.7 8.8 8.7 8.7
8.5 8.5
8.0
7.4 7.5 7.4 7.5
7.3 7.2 7.2 7.1 7.2 7.2 7.2 7.1
7.1 7.0 7.1 7.1 7.1
6.9
7.0 6.8 6.7
6.0
L2T3 INSIGHT TTT TRIPLE 4021 LAPTOP APOLLO INITIATE TULIP Pooled
Therapy n=1,297
Gla, insulin glargine; Met, metformin;
SU, sulfonylurea Owens DR, et al. Diabetes Res Clin Pract 2014;106:264–74 (suppl).
Insulin dose profiles by weight (U/kg)
over time
7.0
Episodes per patient-year
6.0
5.0
4.1 3.9
4.0 3.6
3.0
2.0 1.4 1.3
1.1
1.0 0.5 0.7 0.6
0.2 0.00 0.3 0.005 0.3 0.005
0.0