Ueda2015 type 2 dm management dr.mesbah kamel
Transcript of Ueda2015 type 2 dm management dr.mesbah kamel
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Management in Type 2 DM
Mesbah Sayed Kamel
MD
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The Importance of Tight Glycemic Control
Stratton IM, et al. BMJ 2000; 321: 405-412
Every 1% of HbA1c is important in the reduction of risk in
patients with type 2 diabetes (UKPDS)
Relative risk
(n=3642)
Diabetes-related death
Fatal and nonfatal
myocardial infarction
Microvascular
complications
Amputations or death caused by peripheral
vascular disorders
Per 1% HbA1c
reduction
1%
p<0.001
21%
14%
37%
43%
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Healthy eating, weight control, increased physical activity & diabetes education
Metformin high low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
high low risk
gain
edema, HF, fxs
low
Thiazolidine- dione
intermediate low risk
neutral
rare
high
DPP-4 inhibitor
highest high risk
gain
hypoglycemia
variable
Insulin (basal)
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
Basal Insulin +
Sulfonylurea
+
TZD
DPP-4-i
GLP-1-RA
Insulin§
or
or
or
or
Thiazolidine-dione
+ SU
DPP-4-i
GLP-1-RA
Insulin§
TZD
DPP-4-i
or
or
or
GLP-1-RA
high low risk
loss
GI
high
GLP-1 receptor agonist
Sulfonylurea
high moderate risk
gain
hypoglycemia
low
SGLT2 inhibitor
intermediate low risk
loss
GU, dehydration
high
SU
TZD
Insulin§
GLP-1 receptor agonist
+
SGLT-2 Inhibitor +
SU
TZD
Insulin§
Metformin +
Metformin +
or
or
or
or
SGLT2-i
or
or
or
SGLT2-i
Mono- therapy
Efficacy* Hypo risk
Weight
Side effects
Costs
Dual therapy†
Efficacy* Hypo risk
Weight
Side effects
Costs
Triple therapy
or
or
DPP-4 Inhibitor
+ SU
TZD
Insulin§
SGLT2-i
or
or
or
SGLT2-i
or
DPP-4-i
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote any specific preference - choice dependent on a variety of patient- & disease-specific factors):
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin +
Combination injectable therapy‡
GLP-1-RA Mealtime Insulin
Insulin (basal)
+
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
HbA1c ≥9%
Metformin intolerance or
contraindication
Uncontrolled hyperglycemia
(catabolic features, BG ≥300-350 mg/dl,
HbA1c ≥10-12%)
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Management of Hyperglycemia in
Type 2 Diabetes, 2015:
A Patient-Centered Approach
Update to a Position Statement of the American Diabetes Association (ADA)
and the European Association for the Study of Diabetes (EASD)
Diabetes Care 2015;38:140–149
Diabetologia 2015;58:429–442
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Approach to management
of hyperglycemia: more
stringent
less
stringent
Patient attitude and expected treatment efforts
highly motivated, adherent,
excellent self-care capacities
less motivated, non-adherent,
poor self-care capacities
Risks potentially associated with hypoglycemia, other
adverse events
low high
Disease duration newly diagnosed long-standing
Life expectancy long short
Important comorbidities absent severe few / mild
Established vascular complications
absent severe few / mild
Resources, support system readily available limited
Figure 1 Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
(Adapted with permission from: Ismail-Beigi F, et al. Ann Intern Med 2011;154:554)
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Initial drug monotherapy
Efficacy (! HbA1c)
Hypoglycemia
Weight
Side effects
Costs
Healthy eating, weight control, increased physical activity
Metformin
high
low risk
neutral/loss
GI / lactic acidosis
low
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
Efficacy (! HbA1c)
Hypoglycemia
Weight
Major side effect(s)
Costs
high
low risk
gain
edema, HF, fx’s‡
high
Thiazolidine- dione
intermediate
low risk
neutral
rare‡
high
DPP-4 Inhibitor
highest
high risk
gain
hypoglycemia‡
variable
Insulin (usually basal)
Two drug combinations*
Sulfonylurea†
+
Thiazolidine-dione
+
DPP-4 Inhibitor
+
GLP-1 receptor agonist
+
Insulin (usually basal)
+
Metformin +
Metformin +
Metformin +
Metformin +
Metformin +
TZD
DPP-4-i
GLP-1-RA
Insulin§
SU†
DPP-4-i
GLP-1-RA
Insulin§
SU† SU†
TZD TZD
TZD
DPP-4-i
Insulin§ Insulin§
If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6 months, proceed to a more complex insulin strategy, usually in combination with 1-2 non-insulin agents:
Insulin# (multiple daily doses)
Three drug combinations
More complex insulin strategies
or
or
or
or
or
or
or
or
or
or
or
or GLP-1-RA
high
low risk
loss
GI‡
high
GLP-1 receptor agonist
Sulfonylurea†
high
moderate risk
gain
hypoglycemia‡
low
If needed to reach individualized HbA1c target after ~3 months, proceed to 2-drug combination (order not meant to denote any specific preference):
If needed to reach individualized HbA1c target after ~3 months, proceed to 3-drug combination (order not meant to denote any specific preference):
Adapted Recommendations: When Goal is to Minimize CostsDiabetes Care, Diabetologia. 19 April 2012
[Epub ahead of print]
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SU management in T2DM
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GLIMEPIRIDE
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K+
K+GlimepirideGlibenclamide
Solubilisation
Glibenclamide Glimepiride
65 kDa
140 kDa
65 kDa
140 kDa
cell membrane
Sulfonylurea
receptorPotassium channels
Glimepiride binds to the 65 kDa subunit of the sulfonylurea receptor; glibenclamide binds to the 140 kDa subunit
Kramer W et al., Biochim Biophys Acta 1994;1191: 278-290
Hypothetical Model of Sulfonylurea Receptor in -cells
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1st ActionPancreatic : Insulin Secretion
• Glimepiride binds and dissociates rapidly to a different receptor than other sulfonylureas[1,2]
ee
Ca2+
[Ca2+]
Pancreatic B-cell
vvv
vv
vv v
K+ + ATP
KATP-channel
Insulin
secretion
SULFONYLUREASulfonylureas bind SUR1
receptors on β-cells
Close ATP-sensitive
K+ channels
Increased Ca2+ influx
Insulin-containing secretory
granules translocate to cell
surface
Insulin release[2]
1Kramer W, et al. Biochimica etl Biophysica Acta 1994; 1191: 278-290; 2Rosak C. J Diabetes Complications 2002;16:123-32
Glimepiride binds to SURx
Receptors on β-cellsGlimepiride
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Acting on Both Phases of Insulin Secretion
Glimepiride: The only sulfonylurea to treat
fasting and postprandial hyperglycemia
First Phase Second Phase
Insulin secretion
Before treatment After Glimepiride treatment
Inc
rem
en
tal p
las
ma
in
su
lin
(pm
ol/
L)
0
50
100
p=0.04
First and second phase insulin secretion
before and after treatment with Glimepiride
p=0.02
+Glimepiride
+Glimepiride
Korytkowski M et al. Diabetes Care 2002; 25(9):1607-11.
Euglycemic and
hyperglycemic clamp
studies in 11 obese
patients with T2DM
with good glycemic
control before and after
4 months treatment
with Glimepiride to
assess effect of
Glimepiride on insulin
secretion
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Glimepiride Controls Glycemia with Less Insulin Secretion
• For an equivalent glycemic effect, Glimepiride induces a lower secretion of insulin
Mean variation of insulin and
glycemia over a 36-h period
Mean ratio between increased level
of insulin and reduced glycemia
5
10
15
0
1
2
3
Glimepiride Glibenclamide Gliclazide Glipizide
20
0
Gly
ce
mic
va
ria
tio
n (
%)
Insu
lin
em
ia
(U
/mL)
GlimepirideGlibenclamide Glipizide Gliclazide
0.00
0.05
0.10
0.15
0.20n=16
n=13
n=14
n=16
Ratio
Muller G, et al. Diabetes Res Clin Pract 1995; 28 (Suppl): S115-37
Sulfonylureas tested in
fasted male beagle
dogs to determine
ratios of mean plasma
insulin release/ blood
glucose decrease
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1Müller & Wied. Diabetes. 1993;42: 1852-1867; 2Mori et al. Diabetes Obes Metab 200; epub ahead of print
The extrapancreatic effect of Glimepiride
Rate limiting step for glucose utilization is
glucose uptake via GLUT4 transporter
Glimepiride ↑ translocation of GLUT4
transporters from low-density microsomes
to plasma membrane
of insulin-resistant fat and muscle cells1
Glimepiride ↑ GLUT4 protein and glucose
utilization in oxidative muscles in vivo2
Glimepiride appears to ↑ peripheral
glucose uptake1,2 and to mimic
the action of insulin1
2nd ActionExtra-Pancreatic: Insulin Resistance
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Glimepiride reduces Insulin Resistance
Inukai K, et al. Diabetes Res Clin Pract 2005; 68: 250-257
0
1
2
3
4
5
HOMA-IR
6
6.5
7
7.5
8
HbA1c (%)
Baseline 6 months
Gliclazide or
glibenclamide
(n=52)
all patients BMI ≥ 25 BMI < 25
Glimepiride
(n=120)
all patients BMI ≥ 25 BMI < 25
Glimepiride
(n=120)
*
* *
Mean homeostasis model of insulin resistance (HOMA-IR) and
HbA1c (%) levels at baseline and after 6 months of treatment
*p< 0.05 vs baseline
Glimepiride maintains glycemic control and improves insulin sensitivity in
patients switching from gliclazide or glibenclamide
Gliclazide or
glibenclamide
(n=52)
Multicentre study in 172
Japanese patients in
whom glycemia was
inadequately controlled
(HbA1c ≥7%) by
gliclazide or
glibenclamide. Patients
were randomly assigned
to continue their usual
sulfonylurea or switch to
Glimepiride and were
followed for 6 months.
Baseline HbA1c: 7.5%
gliclazide/glibenclamide
; 7.6% Glimepiride
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Effectiveness of Antidiabetic Agent
DPP-4 = dipeptidyl peptidase 4; TZD = thiazolidinedione.
Nathan DM. N Engl J Med. 2007;356(5):437-440.
1.5 1.5 1.0-1.5 0.5-0.9 0.8-1.0
≥2.5
SUs
Biguanides
(metformin) Glinides
DPP-4
inhibitors TZDs Insulin
0.0
0.5
1.0
1.5
2.0
2.5
3.0
Hb
A1
cR
ed
uc
tio
n (
%)
Efficacy as monotherapy
Antidiabetic agents
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Glimepiride Sustained Glycemic Control
Mean change in HbA1c from baseline
Hb
A1
c (
%)
4 months 12 months 18 months
-1.4*-1.5*
-1.7*
*p<0.0001
Weitgasser R, et al. Diabetes Res Clin Pract 2003; 61(1): 13-9
0
-0.2
-0.4
-0.8
-1.0
-1.2
-1.4
-1.6
-1.8
>1%sustained
reduction
in HbA1c
1% reduction in
HbA1c means 37% reduction in risk of
microvascular complications,
according to UKPDS study
Open-label study in 284 T2DM patients treated with Glimepiride 0.5 to > 4 mg once daily for 1.5 years; baseline HbA1c 8.4%
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Efficacy: Glimepiride + Insulin Combination
• Reduced insulin requirement and faster glycemic control and with insulin + Glimepiride vs insulin + placebo
Randomized, double-
blind, 24-week study in
T2DM subjects with
body weight >130%
ideal and in
secondary
sulfonylurea failure.
Patients were
randomized to
placebo + insulin or
Glimepiride + insulin.
Riddle et al. Diabetes Care 1998;21:1052-1057
* p<0.001; † p<0.05 vs GlimepiridePlacebo + Insulin (n=62) Glimepiride + Insulin (n=70)
Un
its
/da
y
Weeks
0
25
50
75
100
0 4 8 12 16 20 24
†
**
* * * *78 U/day
49 U/day
-38%
Mean insulin dosage required to
restore glycemic control
Weeks
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• Glimipride is an effective tool in management of type2 DM either as monotherapy or added to other non SU drugs or insulin.
• Glimipride addresses more than one pathophysiological target of type 2DM :
increase both 1st&2nd phase of insulin release.
Increase insulin sensitivity.
• Controls Glycemia with Less Insulin Secretion.
• Improve tt.adherence:
once daily,modest cost,less frequent side effects and sustained action.
Sammary
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The most powerful agent we haveto control glucose
Insulin…
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Management of Hyperglycemia in
Type 2 Diabetes, 2015:
A Patient-Centered Approach
Update to a Position Statement of the American Diabetes Association (ADA)
and the European Association for the Study of Diabetes (EASD)
Diabetes Care 2015;38:140–149
Diabetologia 2015;58:429–442
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Add ≥2 rapid insulin* injections before meals ('basal-bolus’†)
Change to premixed insulin* twice daily
Add 1 rapid insulin* injections before largest meal
• Start: Divide current basal dose into 2/3 AM,
1/3 PM or 1/2 AM, 1/2 PM.
• Adjust: é dose by 1-2 U or 10-15% once-
twice weekly until SMBG target reached.
• For hypo: Determine and address cause; ê corresponding dose by 2-4 U or 10-20%.
• Start: 10U/day or 0.1-0.2 U/kg/day
• Adjust: 10-15% or 2-4 U once-twice weekly to
reach FBG target.
• For hypo: Determine & address cause;
ê dose by 4 units or 10-20%.
Basal Insulin (usually with metformin +/- other non-insulin agent)
If not controlled after
FBG target is reached (or if dose > 0.5 U/kg/day),
treat PPG excursions with
meal-time insulin. (Consider initial
GLP-1-RA trial.)
low
mod.
high
more flexible less flexible
Complexity #
Injections
Flexibility
1
2
3+
If not controlled,
consider basal-bolus.
If not controlled,
consider basal-bolus.
• Start: 4U, 0.1 U/kg, or 10% basal dose. If A1c<8%, consider ê basal by same amount.
• Adjust: é dose by 1-2 U or 10-15% once-
twice weekly until SMBG target reached.
• For hypo: Determine and address cause;
ê corresponding dose by 2-4 U or 10-20%.
• Start: 4U, 0.1 U/kg, or 10% basal dose/meal.‡ If
A1c<8%, consider ê basal by same amount.
• Adjust: é dose by 1-2 U or 10-15% once-twice
weekly to achieve SMBG target.
• For hypo: Determine and address cause; ê corresponding dose by 2-4 U or 10-20%.
Figure 3. Approach to starting & adjusting insulin in T2DM
Diabetes Care 2015;38:140-149;
Diabetologia 2015;58:429-442
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• The risk for hypoglycemia in type 2 diabetes is low, and newer insulin analogs have demonstrated even lower rates of hypoglycemia than older insulin products.
• Although weight gain can be expected with insulin (similar to that seen with secretagogues), the benefits of glycemic control clearly exceed the small increases in body weight.
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• Of note, insulin has been shown to reduce mortality postmyocardial infarction,and more than 10 years of follow-up in the United Kingdom Prospective Diabetes Study (UKPDS) have clearly shown no increase in cardiovascular risk.
• Finally, although multiple daily injections may be required for patients with advanced, uncontrolled diabetes, simpler insulin regimens are often highly effective if initiated earlier in the course of diabetes
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Basal Insulin Therapy
• Usual first step in beginning insulin therapy
• Continue oral agents and add basal insulin to optimize FPG
• A1C of up to 9.0% usually brought to goal (7%) by addition of basal insulin therapy to oral agents
• Easy and generally safe: patient-directed treatment algorithms with small risk of serious hypoglycemia
ADA=American Diabetes Association; EASD=European Association for the Study of Diabetes.
ADA/EASD Management of hyperglycemia in type 2 diabetes: A patient-centered approach. Diabetologia (2012) 55:1577–1596
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Types of basal insulin
Intermediate-Acting
(e.g. NPH, lente)
Long-Acting (e.g. ultralente)
Long-Acting Analogues
(glargine, detemir)
Onset 1-3 hr(s) 3-4 hrs 1.5-3 hrs
Peak 5-8 hrs 8-15 hrsNo peak with glargine, dose-dependent peak
with detemir
Duration Up to 18 hrs 22-26 hrs9-24 hrs (detemir); 20-24 hrs (glargine)
Rossetti P, et al. Arch Physiol Biochem 2008;114(1): 3 – 10.
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• Recombinant human insulin analogue1
• Basal (long-acting) insulin1
• Relatively constant peakless concentration/time profile over 24 hours1,2
• Once-daily SC administration1
• For adult and paediatric (aged 6 years) patients with type 1 diabetes2 and adults with type 2 diabetes
• Less nocturnal hypoglycaemia1
• More flexible dosing1
Insulin Glargine
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Insulin Glargine Structure
1. Lantus® (insulin glargine) EMEA Summary of Product Characteristics. 2002.
2. McKeage K et al. Drugs. 2001;61:1599-1624.
Substitution
Extension
A chain
B chain
1
15105
10 15
20 Asn
30
Gly
Arg Arg
5 10 15 19 25
1
• Asparagine at position A21 replaced by glycine
– Provides stability
• Addition of 2 arginines at the C-terminus of the B chain
– Soluble at slightly acidic pH
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Injection of an acidic solution(pH 4.0)3
Microprecipitation of insulin glargine
in subcutaneous tissue (pH 7.4)3
Slow dissolution of free insulin glargine hexamers from microprecipitates (stabilised aggregates)3
Protracted action3
1. Lantus® (insulin glargine) EMEA Summary of Product Characteristics. 2002.
2. McKeage K et al. Drugs. 2001;61:1599-1624.
3. Kramer W. Exp Clin Endocrinol Diabetes. 1999;107(suppl 2):S52-S61.
Insulin Glargine Mechanism of Action
The mechanics of sustained release1,2
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PK/PD: Insulin Glargine has a flatter action profile and a longer duration of action than NPH
Lepore M, et al. Diabetes 2000;49(12):2142–2148
Randomized four-way crossover euglycaemic clamp study comparing
the pharmacokinetics and pharmacodynamics of Insulin Glargine with
three commonly used basal insulin regimens (NPH, ultralente, CSII) in
patients with T1DM
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Insulin glargine consistently achieves mean HbA1C ≤ 7%
1. Riddle M, et al. Diabetes Care 2003;26:3080. 2. Gerstein HC, et al. Diabetes Med 2006;23:736. 3. Bretzel RG, et al. Lancet 2008;371:1073. 4. Yki-Järvinen H, et al. Diabetes Care 2007;30:1364. 5. Schreiber SA, et al. Diabetes Obes Metab 2007;9:31.
Baseline Study end
5.5
6.0
6.5
7.0
7.5
8.0
8.5
9.0
9.5
T-T-T1
(n = 367)INSIGHT2
(n = 206)APOLLO3
(n = 174)INITIATE4
(n = 58)Schreiber5
(n = 12,216)
Hb
A1
C(%
)
8.6 8.6 8.7 8.78.8
7.0 7.0 7.0 6.8 7.0
∆ -1.6 ∆ -1.6 ∆ -1.7 ∆ -2.0 ∆ -1.7
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Reduced risk of nocturnal hypoglycaemia with insulin glargine
NPH
Insulin glargine
p<0.001
p<0.002
Events
per
pati
ent–
year
All nocturnal
hypoglycaemiaConfirmed nocturnal
hypoglycaemia
p<0.001
* **
Confirmed hypoglycaemia: *4 mmol/l (72 mg/dl); **3.1 mmol/l (56 mg/dl) Riddle M. et al. Diabetes Care 2003;26:3080–6.
44%
risk reduction
42%
risk reduction
48%
risk reduction
6.9
5.5
2.5
4.0
3.1
1.3
0
1
2
3
4
5
6
7
8
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33
Treat-to-Target: Insulin Glargine can be rapidly titrated to achieve target glycaemic control
Starting daily dose
10 IU
Forced weekly titration using
predefined algorithm and
based on self-monitored FBGRiddle MC, et al. Diabetes Care 2003;26(11):3080–3086
Mean daily dose at endpoint (IU/kg)
• NPH: 0.42
• Insulin Glargine: 0.48
• Randomized study in 756 insulin-naïve patients with T2DM who added
Insulin Glargine or NPH to their existing OAD therapy
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•Basal insulin begun at a low dose (e.g., 0.1–0.2 units/kg per
day).
• A single injection of basal insulin administered before the
evening meal or at bedtime, at an initial dose of 0.1units/kg.
This will ensure that changes in blood glucose levels will be
gradual.
• Under special conditions, such as significant hyperglycemia
(HbA1c ≥9%) and/or obesity, a starting dose of 0.2 units/kg
may be used.
•An alternative, non-weight-based option is to start most
individuals empirically with 10 units, or in obesity up to 20
units, of basal insulin (i.e., long-acting or intermediate-acting).
How to Initiate Basal Insulin
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Initiate& Titrate basal insulin
FPG, fasting plasma glucose
Nathan DM, et al. Diabetes Care 2009;32:193-203.
Initiate insulin with a single injection of a basal insulin
(Glargine)
CheckFPGdaily
In the event of hypoglycemia or FPG level <3.89 mmol/L(<70 mg/dL)
• Reduce bedtime insulin dose by 4 units, or by 10% if >60 units
• Bedtime or morning long-acting insulin OR
• Bedtime intermediate-acting insulin
Daily dose: 10 units or 0.2 units/kg
INITIATE
• Increase dose by 2 units every 3 days until FPG (70–130 mg/dL)
• If FPG is >180 mg/dL, increase dose by 4 units every 3 days
TITRATE
Continue regimen and check HbA1c every 3 monthsMONITOR
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1.2.3 study: insulin glargine with addition of one, two or
three daily doses of glulisine
Subjects:• Insulin naïve (785 entered study, 343 randomized) T2D (HbA1c ≥8.0%)
• Receiving 2 or 3 OHAs for ≥3 months (OHAs continued except sulfonylurea)
Randomization (subjects
with HbA1c >7.0%, n=434)
24 weeks
Insulin glargine
(n=785)
14 weeks
Additional insulin glulisine once daily (n=115)
Additional insulin glulisine twice daily (n=113)
Additional insulin glulisine three times daily (n=115)
Sanofi-aventis data on file (1.2.3 study)
Mean study entry values:
• HbA1c (%): 9.8
• BMI (kg/m2): 35.0
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1.2.3 study: intensification of Basal insulinwith mealtime glulisine injections improves glycemic
control
Sanofi-aventis data on file (1.2.3 study)
HbA1c in all subjects (n=785) = 9.8 at run in and 7.3 at randomization
Run in Randomization Wk 8 Wk 16 Wk 24
7.40
7.0
Hb
A1
c (%
)
10.19
10.1910.16
7.44
7.29
8.0
9.0
10.0
Glulisine 1x
Glulisine 2x
Glulisine 3x
Responders in the whole
population (n=785)
Evolution of HbA1c in the
randomized population (n=343)
0
20
40
60
80
Subjects who
achieved
HbA1c <7.0%
with glargine
during run in
Additional
subjects who
achieved
HbA1c <7.0%
with glulisine
added to
glargine
All subjects
(n=785)
% a
ch
ievin
g H
bA
1c
<7.0
23%
37%
Glargine
(alone)
Glargine plus glulisine
(patients with HbA1c >7%)
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1.2.3 study: The Basal Plus strategy is associated with a reduced level of hypoglycaemia
p=NS for all other pairwise comparisons
Sanofi-aventis data on file (1.2.3 study)
x1 x2 x30
1
2
3
4
5
Mean
bo
dy w
eig
ht
ch
an
ge
fro
m b
aselin
e (
kg
)
3.7 3.8 3.9
Glulisine
0
5
10
15
20
x1 x2 x3
Glulisine
Co
nfi
rmed
sym
pto
ma
tic h
yp
o
(even
t/p
ati
en
t-year)
12.212.9
17.1
p=0.043
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
Severe
or
seri
ou
s h
yp
o
(even
t/p
ati
en
t-year)
x1 x2 x3
Glulisine
0.10
0.30
0.26
•At study end, the mean insulin dose (glargine + glulisine) was 84 +27, 80 + 50
and 81 + 66 U/day in the glulisine x1, x2 and x3 groups, respectively.
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Summary
• Early and Tight management of type 2 DM is highly recommended to avoid complications.
• Individualize treatment based upon patient needs, resources, and lifestyle considerations
• CVS Safety issue must be considered in all patients.
• Structured patient Education &SMBG can minimize the hypoglycemia.
• Overcome the causes for patient resistance to insulin therapy with provider belief and communication strategies
• Recognize when prandial insulin is required to avoid clinical inertia and the concept of overbasalization
• Be willing to change strategies as needed to achieve goals i.e:
AVOID CLINICAL INNERTIA
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THANK YOU