Ueda2015 type 2 dm management dr.mesbah kamel

Management in Type 2 DM

Mesbah Sayed Kamel

MD

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%

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%)

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

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)

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]

SU management in T2DM

GLIMEPIRIDE

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

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

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

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

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

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

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

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%

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

• 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

The most powerful agent we haveto control glucose

Insulin…

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

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

• 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.

23

• 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

24

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

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.

• 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

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

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

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

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

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

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

•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

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

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

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%)

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.

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

THANK YOU