getting to goal

7/30/2019 Getting to Goal

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Canadian Diabetes Association2003 Clinical Practice Guidelines

for the Prevention and Management

of Diabetes in Canada

This material has been reviewed by the Canadian Diabetes Association for its medical and scientific accuracy.Presence of the Canadian Diabetes Association Partners in Progress mark does not constitute an endorsement of the products or services of GlaxoSmithKline Inc.

Getting to Goalin Type 2 Diabetes


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1 Harris S, et al, The Diabetes in Canada Evaluation (DICE) Study, ADA 2003, 2162-PO2 Harris MI, et al. Diabetes Care1999; 22:403408.

P

ercentageofsubjects

0

20

40

60

80

100

7%

A1C (%)

US (1988-1994)2

Many patients have inadequate glycemic control

38%

62%

P

ercentageofs

ubjects

0

20

40

60

80

100

< 7% 7%

A1C (%)

CAN (2003)1

50% 50%


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Years T2DM

Proportion of patients with A1C > 7.0increases with duration of type 2 diabetes


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Proportion of patients with hypertensionincreases with duration of type 2 diabetes

Years T2DM


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Proportion of patients with dyslipidemiaincreases with duration of type 2 diabetes

Years T2DM


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Proportion of patients with cardiovascular diseaseincreases with duration of type 2 diabetes

Years T2DM


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Proportion of patients with microvascular diseaseincreases with duration of type 2 diabetes

Years T2DM


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The evolution of management guidelines

Studies including UKPDS have highlighted the

importance of glycemic control in reducing complications

New guidelines include tighter targets for glycemic control Guidelines recognize importance of treating all aspects

of the condition

Current guidelines therefore include targets for

glycemic control

lipid levels

blood pressure


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Adapted from Stratton IM, et al. UKPDS 35. BMJ2000; 321:405412.

UKPDS: decreased risk of diabetes-related complications

associated with a 1% decrease in A1C

Percentagedecrease

inrelativerisk

corre

spondingtoa1%d

ecreaseinHbA1C

**

Any

diabetes-

related

endpoint

21%

**

Diabetes-

related

death

21% **

All

cause

mortality

14%

*

Stroke

12%

**

Peripheral

vascular

disease

43%

**

Myocardialinfarction

14%

**

Micro-

vascular

disease

37%

**

Cataract

extraction

19%

Observational analysis from UKPDS study data

Lower extremity amputation or fatal peripheral vascular disease

*P= 0.035; **P< 0.0001


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Stratton IM, et al. UKPDS 35. BMJ2000; 321:405412.

UKPDS: the benefits of improved

glycemic control

Improved glycemic control significantly reduces risk

of diabetes-related complications

UKPDS results indicated that a 1% reduction in A1Cwould reduce the risk of microvascular complications

by 37%, but have less effect (16%) on

macrovascular complications

Further improvement in sustained glycemic controland reduction in the burden of cardiovascular

disease are needed


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06

7

8

9

2 4 6 8 10

A1C(%)

Years from randomization

Upper limit of of normal = 6.2%

ConventionalGlyburideChlorpropamideMetforminInsulin

0

UKPDS demonstrated loss of glycemic

control with all agents studied

UK Prospective Diabetes Study Group. UKPDS 34. Lancet1998; 352:854865.

Overweight patients

Cohort, median values


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Turner RC, et al. UKPDS 49. JAMA 1999;281:20052012.

100

Years from randomization

3 6 90

20

40

60

80

3 6 9 3 6 9 3 6 9

Diet Insulin MetforminSulfonylurea

Overweight patients

Proportionofp

atients(%)

50%

Proportion of patients with A1C < 7.0% onmonotherapy at 3, 6 and 9 years

Error bars = 95% CI


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The UKPDS demonstrated progressive

decline of-cell function over time

100

80

60

40

P< 0.0001

HOMA model, diet-treated n = 376

Time from diagnosis (years)

100

-cellfunctio

n(%) 80

60

40

20

0

Start of treatment

Adapted from Holman RR. Diabetes Res Clin Pract1998; 40 (Suppl.):S21S25.

10 9 8 7 6 5 4 3 2 1 1 2 3 4 5 6


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Canadian Diabetes Association

2003 Clinical Practice Guidelinesfor the Prevention and Management


Glycemic Targets


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CMAJ 1998; 159 (8 Suppl):S1-29

1998 CDA Treatment Targets

Level

Ideal(normalnondiabetic)

Optimal*(target goal) Suboptimal

(action maybe required)

Inadequate

(actionrequired)

GlycatedHb(% of upperlimit)e.g., HbA1cassay

10

Glucose level1-2 h after meal(mmol/L)

4.4-7 5.0-11 11.1-14 >14

Hb = hemoglobin

*These levels are likely related to minimal long-term complications but may be impossible to achieve in most paients with type 1 diabetes with current therapies

Attainable in the majority of people with diabetes but may not be adequate to prevent compicationsThese levels are related to a markedly increased risk of long-term complications, requiring a reassessment and readjustment of therapy


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A1C**(%)

FPG/preprandial PG(mmol/L)

2-hour postprandial PG(mmol/L)

Target for most patients 7.0 4.0-7.0 5.0-10.0

Normal range(considered for patientsin whom it can beachieved safely)

6.0 4.0-6.0 5.0-8.0

A1C = glycosylated hemoglobin

DCCT = Diabetes Control and Complications Trial

FPG = fasting plasma glucose

PG = plasma glucose

2003 CDA Recommended Targets for

Glycemic Control


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Components of Glycemic Control

2 h. PostprandialPlasma Glucose

5-10 mmol/L5-8 mmol/L*

Fasting/PreprandialPlasma Glucose

4-7 mmol/L4-6 mmol/L*

A1C


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Canadian Diabetes Association

2003 Clinical Practice Guidelinesfor the Prevention and Management


Management of Hyperglycemia

in Type 2 Diabetes


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Lifestyle Intervention

The first step in treating type 2 diabetes

Nutrition therapy and exercise can improve glycemic control

Success of lifestyle intervention related to:

patients initial fasting plasma glucose level

amount of weight loss achieved by patient

Only a minority of patients are able to attain treatment

targets using lifestyle intervention alone.


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UKPDS 7: Response of FPG to Diet

Therapy in Newly Diagnosed Patients

N= 3044, newly diagnosed patients

FPG at diagnosis 12.1+/- 3.7 mmol/L

Diet counseling

Patients with FPG 10-12 mmol/L needed reduction of 28%ideal body weight; to attain FPG


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Antihyperglycemic Agents


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Glucose (G)

Insulin

I

I

I

Adipose tissue

Liver

Pancreas

Muscle

Gut

Carbohydrate

Stomach -glucosidase inhibitors

Insulinsecretagogues

Biguanides

Thiazolidinediones

Primary Sites of Action of Oral

Antihyperglycemic Agents

Adapted from Kobayashi M. Diabetes Obes Metab1999; 1 (Suppl. 1):S32S40.Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol Metab1999; 13:309329.


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Key Recommendations

Antihyperglycemic agents should be initiated if glycemic targetsnot met after 2-3 months of lifestyle intervention

Antihyperglycemic agents should be started concomitantly withlifestyle if A1C levels are greater than 9%

The lag period before adding other agent(s) should be kept to aminimum to achieve glycemic targets within 6-12 months

Unless contraindicated, metformin should be used first line;

other agents should be considered in the order they appear inthe treatment algorithm

Insulin therapy should be initiated if targets cannot be achievedwith lifestyle changes and oral therapy


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Diet/exercise

Oralmonotherapy

Oralcombination

Insulin

Early aggressivecombination therapy as required

Stepwise treatment

Oral+/- insulin

New Treatment Options for

Type 2 Diabetes


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Management of Hyperglycemia in

Type 2 Diabetes

Clinical assessment and initiation of nutrition and physical activity

Overweight(BMI 25 kg/m2)

Non-overweight(BMI 25 kg/m2)

Mild to moderate hyperglycemia (A1C


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Add a drug from a different classor

Use insulin alone or in combination with:

biguanide insulin secretagogue

insulin sensitizer* alpha-glucosidase inhibitor

Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months

If not at target

* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin iscurrently not an approved indication in Canada.

Overweight (BMI 25 kg/m2)



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Dose-Effect RelationshipDose-Effect RelationshipDose-Effect Relationship

Riddle M. Combiningsulfonylureas and other oral agents.Am J of Med. 2000; 108(6A):15S-22S.

Graph of theoretical dose-effect relationship for many drugs, showing thathalf-maximal dosages yield far more than 50% of the therapeutic effectsand that side effects can increase as the dosage nears maximal levels.

Maximal

Half-maximal

Half-maximal Maximal

Therapeutic effect

Side effect

Effect

Dose


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Dose-Response CurveDose-Response CurveDose-Response Curve

Riddle M. Combiningsulfonylureas and other oral agents.Am J of Med. 2000; 108(6A):15S-22S.

Dose-response curve showing GI related effects

30

20

10

0 500 1000 1500 2000 25000

0.5

1.0

1.5

2.0

Dose

GIDistress

Patients(%)

Reductionvs.placebo,

HbA1

c(%)


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Non-overweight (BMI 25 kg/m2)



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Marked hyperglycemia (A1C 9.0%)

2 antihyperglycemic agents from different classes

biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor

Add an oral antihyperglycemic agentfrom a different class or insulin*


If not at target

* When used in combination with insulin, insulin sensitizers may increase the risk of edema or CHF. The combination of an insulin sensitizer and insulin is

currently not an approved indication in Canada. May be given as a combined formulation: rosiglitazone and metformin (Avandamet TM)

L

I

F

E

S

T

Y

L

E


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Basal and/or preprandial insulin


currently not an approved indication in Canada.* *If using preprandial insulin, do not add an insulin secretagogue.

L

I

F

E

S

T

Y

L

E

Intensify insulin regimen or add

biguanide insulin secretagogue** insulin sensitizer*

alpha-glucosidase inhibitorTimely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months

If not at target

Cli i l t d i iti ti f t iti d h i l ti it


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A1C 9%

Consider insulin at any stage of treatment

Vascular protection to further reduce cardiovascular risk

Key Changes


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Canadian Diabetes Association2003 Clinical Practice Guidelines

for the Prevention and Management


This material has been reviewed by the Canadian Diabetes Association for its medical and scientific accuracy.

Presence of the Canadian Diabetes Association Partners in Progress mark does not constitute an endorsement of the products or services of GlaxoSmithKline Inc.

Getting to Goalin Type 2 Diabetes


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Supplementary Slides:Key Recommendations


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In people with type 2 diabetes, if glycemic targets are

not achieved using lifestyle management within 2 to 3

months, antihyperglycemic agents should be initiated[Grade A, Level 1A ]. In the presence of marked

hyperglycemia (A1C > 9.0%), antihyperglycemic

agents should be initiated concomitant with lifestyle

counselling [Grade D, Consensus].

Recommendation 1


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If glycemic targets are not attained when a single

antihyperglycemic agent is used initially, an

antihyperglycemic agent or agents from otherclasses should be added. The lag period before

adding other agent(s) should be kept to a minimum,

taking into account the pharmacokinetics of the

different agents. Timely adjustments to and/oradditions of antihyperglycemic agents should be

made in order to attain target A1C within 6 to 12

months [Grade D, Consensus].

Recommendation 2


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Recommendation 3

This choice of antihyperglycemic agent(s) should takeinto account the individual and the following factors:

Unless contraindicated, a biguanide (metformin)

should be the primary drug used in overweight patients

[Grade A, Level 1A];and

Other classes of antihyperglycemic agents may

be used either alone or in combination to attain

glycemic targets, with consideration given to theinformation in Table 1 and Figure 1 [Grade D,

Consensus for the order of antihyperglycemic agents

listed in Figure 1].


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Recommendation 4

In people with type 2 diabetes, if individual treatment

goals have not been reached with a regimen of

nutrition therapy, physical activity and sulfonylurea[Grade A, Level 1A], sulfonylurea plus metformin

[Grade A, Level 1A]or other oral antihyperglycemic

agents [Grade D, Consensus], insulin therapy should

be initiated to improve glycemic control.


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Recommendation 5

Combining insulin and the following oral antihyperglycemic

agents (listed in alphabetical order) has been shown to be

effective in people with type 2 diabetes:

alpha-glucosidase inhibitors (acarbose) [Grade A, Level 1A]

biguanide (metformin) [Grade A, Level 1A]

Insulin secretagogues (sulfonylureas) [Grade A, Level 1A]

Insulin sensitizers (thiazolidinediones) [Grade A, Level 1A]

(The combination of an insulin sensitizer plus insulin is

currently not an approved indication in Canada.)


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Recommendation 6

Insulin may be used as initial therapy in type 2 diabetes

[Grade A, Level 1A], especially in cases of marked

hyperglycemia (A1C > 9.0%) [Grade D, Consensus].


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Recommendation 7

To safely achieve optimal postprandial glycemic

control, mealtime insulin lispro or insulin aspart is

preferred over regular insulin [Grade B, Level 2].


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Recommendation 8

When insulin given at night is added to oral

antihyperglycemic agents, insulin glargine may be

preferred over NPH to reduce overnighthypoglycemia [Grade B, Level 2]and weight gain

[Grade B, Level 2 ].


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Recommendation 9

All individuals with type 2 diabetes currently using or

starting therapy with insulin or insulin secretagogues

should be counselled about the recognition andprevention of drug-induced hypoglycemia [Grade D,

Consensus].


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Supplementary Slides:Alternate Animation for

Treatment Algorithm



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biguanide insulin secretagogue

insulin sensitizer* alpha-glucosidase inhibitor

Overweight (BMI 25 kg/m2)



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biguanide

insulin secretagogueinsulin sensitizer* alpha-glucosidase inhibitor

Non-overweight (BMI 25 kg/m2)



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Add an oral antihyperglycemic agentfrom a different class or insulin*



2 antihyperglycemic agents from different classes

biguanide insulin sensitizer* insulin secretagogue insulin alpha-glucosidase inhibitor

If not at target


currently not an approved indication in Canada. May be given as a combined formulation: rosiglitazone and metformin (Avandamet TM)

L

I

F

E

S

T

Y

L

E



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Basal and/or preprandial insulin

If not at target

Intensify insulin regimen or add

biguanide insulin secretagogue** insulin sensitizer* alpha-glucosidase inhibitor

L

I

F

E

S

T

Y

L

E

getting to goal

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