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Canadian Diabetes Association2003 Clinical Practice Guidelines
for the Prevention and Management of Diabetes in Canada
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 Goal in Type 2 Diabetes
Getting to Goal in 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 Care 1999; 22:403–408.
Per
cen
tag
e o
f su
bje
cts
0
20
40
60
80
100
<7% > 7%
A1C (%)
US (1988-1994)2
Many patients have inadequate glycemic controlMany patients have inadequate glycemic control
38%
62%
Per
cen
tag
e o
f su
bje
cts
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 > 7.0 increases with duration of type 2 diabetes
Proportion of patients with A1C > 7.0 increases with duration of type 2 diabetes
<=2<=2 3-53-5 6-96-9 10-1410-14 15+15+
31%31%
42%42%
53%53%
67%67%
62%62%
Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.
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Proportion of patients with hypertension increases with duration of type 2 diabetesProportion of patients with hypertension
increases with duration of type 2 diabetes
Years T2DM
<=2<=2 3-53-5 6-96-9 10-1410-14 15+15+
53%53%57%57%
64%64%
71%71% 72%72%
Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.
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Proportion of patients with dyslipidemia increases with duration of type 2 diabetes
Proportion of patients with dyslipidemia increases with duration of type 2 diabetes
Years T2DM
<=2<=2 3-53-5 6-96-9 10-1410-14 15+15+
55%55% 57%57% 58%58% 59%59%
66%66%
Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.
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Proportion of patients with cardiovascular disease increases with duration of type 2 diabetes
Proportion of patients with cardiovascular disease increases with duration of type 2 diabetes
Years T2DM
<=2<=2 3-53-5 6-96-9 10-1410-14 15+15+
15%15%
21%21%24%24%
29%29%
48%48%
Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.
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Proportion of patients with microvascular disease increases with duration of type 2 diabetes
Proportion of patients with microvascular disease increases with duration of type 2 diabetes
Years T2DM
<=2<=2 3-53-5 6-96-9 10-1410-14 15+15+
21%21%
32%32%
42%42% 44%44%
62%62%
Harris,S et al. CDA 2003; Type 2 Diabetes and Associated Complications in Primary Care in Canada: The Impact of Duration of Disease on Morbidity Load.
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The evolution of management guidelinesThe 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
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. BMJ 2000; 321:405–412.
UKPDS: decreased risk of diabetes-related complications associated with a 1% decrease in A1C
UKPDS: decreased risk of diabetes-related complications associated with a 1% decrease in A1C
Per
cen
tag
e d
ecre
ase
in r
ela
tive
ris
k co
rres
po
nd
ing
to
a 1
% d
ecre
ase
in H
bA
1C
**
Any diabetes-related endpoint
21%
**
Diabetes-related death
21% **
All cause
mortality
14%*
Stroke
12%
**
Peripheral vascular disease†
43%
**
Myocardial infarction
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. BMJ 2000; 321:405–412.
UKPDS: the benefits of improved glycemic control
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 A1C would reduce the risk of microvascular complications by 37%, but have less effect (16%) on macrovascular complications
Further improvement in sustained glycemic control and reduction in the burden of cardiovascular disease are needed
Improved glycemic control significantly reduces risk of diabetes-related complications
UKPDS results indicated that a 1% reduction in A1C would reduce the risk of microvascular complications by 37%, but have less effect (16%) on macrovascular complications
Further improvement in sustained glycemic control and reduction in the burden of cardiovascular disease are needed
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06
7
8
9
2 4 6 8 10
A1
C (
%)
Years from randomization
Upper limit of of normal = 6.2%
ConventionalGlyburideChlorpropamideMetforminInsulin
0
UKPDS demonstrated loss of glycemic control with all agents studied
UKPDS demonstrated loss of glycemic control with all agents studied
UK Prospective Diabetes Study Group. UKPDS 34. Lancet 1998; 352:854–865.
Overweight patientsCohort, median values
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Turner RC, et al. UKPDS 49. JAMA 1999; 281:2005–2012.
100
Years from randomization3 6 9
0
20
40
60
80
3 6 9 3 6 9 3 6 9
Diet Insulin MetforminSulfonylurea
Overweight patients
Pro
po
rtio
n o
f p
atie
nts
(%
)
50%
Proportion of patients with A1C < 7.0% on monotherapy at 3, 6 and 9 years
Proportion of patients with A1C < 7.0% on monotherapy at 3, 6 and 9 years
Error bars = 95% CI
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The UKPDS demonstrated progressive decline of -cell function over time
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
-ce
ll f
un
ctio
n (
%) 80
60
40
20
0
Start of treatment
Adapted from Holman RR. Diabetes Res Clin Pract 1998; 40 (Suppl.):S21–S25.
–10 –9 –8 –7 –6 –5 –4 –3 –2 –1 1 2 3 4 5 6
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Canadian Diabetes Association2003 Clinical Practice Guidelines
for the Prevention and Management of Diabetes in Canada
Canadian Diabetes Association2003 Clinical Practice Guidelines
for the Prevention and Management of Diabetes in Canada
Glycemic TargetsGlycemic Targets
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CMAJ 1998; 159 (8 Suppl):S1-29
1998 CDA Treatment Targets1998 CDA Treatment Targets
Level
Ideal(normal
nondiabetic)
Optimal*(target goal)
Suboptimal †
(action maybe required)
Inadequate ‡
(actionrequired)
Glycated Hb(% of upperlimit)e.g., HbA1cassay
<100(.04-.06)
<115(<0.07)
116-140(.07-8.4)
>140(>0.084)
Fasting orpremeal glucoselevel (mmol/L)
3.8-6.1 4-7 7.1-10 >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 compications‡These 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 patients in whom it can beachieved safely)
6.0 4.0-6.0 5.0-8.0
A1C = glycosylated hemoglobinDCCT = Diabetes Control and Complications TrialFPG = fasting plasma glucosePG = plasma glucose
2003 CDA Recommended Targets for Glycemic Control
2003 CDA Recommended Targets for Glycemic Control
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Components of Glycemic ControlComponents of Glycemic Control
2 h. Postprandial Plasma Glucose
5-10 mmol/L5-8 mmol/L*
2 h. Postprandial Plasma Glucose
5-10 mmol/L5-8 mmol/L*
Fasting/PreprandialPlasma Glucose
4-7 mmol/L4-6 mmol/L*
Fasting/PreprandialPlasma Glucose
4-7 mmol/L4-6 mmol/L*
A1C
<7%, <6%* A1C
<7%, <6%*
*If can be achieved safely
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Canadian Diabetes Association2003 Clinical Practice Guidelines
for the Prevention and Management of Diabetes in Canada
Canadian Diabetes Association2003 Clinical Practice Guidelines
for the Prevention and Management of Diabetes in Canada
Management of Hyperglycemiain Type 2 Diabetes
Management of Hyperglycemiain Type 2 Diabetes
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Lifestyle InterventionLifestyle Intervention
The first step in treating type 2 diabetes
Nutrition therapy and exercise can improve glycemic control
Success of lifestyle intervention related to: patient’s 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.
The first step in treating type 2 diabetes
Nutrition therapy and exercise can improve glycemic control
Success of lifestyle intervention related to: patient’s 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 PatientsUKPDS 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 <6 mmol/L 16% achieved FPG <6 after 3 months:
in the group presenting with FPGs of 6-8 mmol/L 50% met this target in the group presenting with FPGs of 16-22 mmol/L only 10% were successful
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 <6 mmol/L 16% achieved FPG <6 after 3 months:
in the group presenting with FPGs of 6-8 mmol/L 50% met this target in the group presenting with FPGs of 16-22 mmol/L only 10% were successful
Metabolism, 1990; 39(3): 905-912
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Antihyperglycemic AgentsAntihyperglycemic Agents
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Glucose (G)
Insulin
I
I
I
II
I
I
I
G
G
GG
G
G
G
GI
G
GG
Adipose tissue
Liver
Pancreas
Muscle
Gut
IG
Carbohydrate
Stomach -glucosidase inhibitors
Insulin secretagogues
Biguanides
Thiazolidinediones
Primary Sites of Action of Oral Antihyperglycemic Agents
Primary Sites of Action of Oral Antihyperglycemic Agents
Adapted from Kobayashi M. Diabetes Obes Metab 1999; 1 (Suppl. 1):S32–S40.Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol Metab 1999; 13:309–329.
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Key RecommendationsKey Recommendations
• Antihyperglycemic agents should be initiated if glycemic targets not met after 2-3 months of lifestyle intervention
• Antihyperglycemic agents should be started concomitantly with lifestyle if A1C levels are greater than 9%
• The lag period before adding other agent(s) should be kept to a minimum 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 in the treatment algorithm
• Insulin therapy should be initiated if targets cannot be achieved with lifestyle changes and oral therapy
• Antihyperglycemic agents should be initiated if glycemic targets not met after 2-3 months of lifestyle intervention
• Antihyperglycemic agents should be started concomitantly with lifestyle if A1C levels are greater than 9%
• The lag period before adding other agent(s) should be kept to a minimum 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 in the treatment algorithm
• Insulin therapy should be initiated if targets cannot be achieved with lifestyle changes and oral therapy
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Diet/exercise
Oralmonotherapy
Oral combination
Insulin
Early aggressivecombination therapy as required
Stepwise treatment
Oral +/- insulin
New Treatment Options for Type 2 Diabetes
New Treatment Options for Type 2 Diabetes
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Management of Hyperglycemia in Type 2 Diabetes
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 <9.0%) Marked hyperglycemia (A1C 9.0%)
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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 is currently not an approved indication in Canada.
Overweight (BMI 25 kg/m2)
Mild to moderate hyperglycemia (A1C <9.0%)
Biguanide alone or in combination with 1 of:• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
L
I
F
E
S
T
Y
L
E
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Dose-Effect RelationshipDose-Effect RelationshipDose-Effect Relationship
Riddle M. Combining sulfonylureas and other oral agents. Am J of Med. 2000; 108(6A):15S-22S.
Graph of theoretical dose-effect relationship for many drugs, showing that half-maximal dosages yield far more than 50% of the therapeutic effects and that side effects can increase as the dosage nears maximal levels.
Maximal
Half-maximal
Half-maximal Maximal
Therapeutic effect
Side effect
Eff
ect
Dose
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Dose-Response CurveDose-Response CurveDose-Response Curve
Riddle M. Combining sulfonylureas 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 2500
0
0.5
1.0
1.5
2.0
Dose
GI
Dis
tre
ss
Pa
tie
nts
(%
)
Re
du
cti
on
vs
. p
lac
eb
o,
Hb
A 1c
(%)
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Non-overweight (BMI 25 kg/m2)
Mild to moderate hyperglycemia (A1C <9.0%)
1 or 2† antihyperglycemic agents from different classes• biguanide• insulin sensitizer*• insulin secretagogue• insulin• 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
Add a drug from a different classor
Use insulin alone or in combination with:
• biguanide• insulin secretagogue• insulin sensitizer*• alpha-glucosidase inhibitor
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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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*
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 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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Marked hyperglycemia (A1C 9.0%)
Basal and/or preprandial insulin
* 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.* * 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 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
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Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight(BMI 25 kg/m2)
Non-overweight(BMI 25 kg/m2)
Biguanide alone or incombination with 1 of:
• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
1 or 2† antihyperglycemicagents from differentclasses
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Add a drug from a different class orUse insulin alone or in combination with:
• biguanide• insulin secretagogue• insulin sensitizer*• alpha-glucosidase inhibitor
Marked hyperglycemia (A1C 9.0%)
2 antihyperglycemic agentsfrom different classes †
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Basal and/orpreprandial insulin
Add an oral
antihyperglycemic agentfrom a differentclass or insulin*
Intensify insulinregimen or add
• biguanide• insulin secretagogue**• insulin sensitizer*• alpha-glucosidase inhibitor
If not at targetIf not at targetIf not at targetIf not at target
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
L
I
F
E
S
T
Y
L
E
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• A1C <7% (< 6% if can be achieved safely)
• Aim to achieve targets within 6-12 months
• Start with combination therapy or insulin for patients with A1C > 9%
• Consider insulin at any stage of treatment
• Vascular protection to further reduce cardiovascular risk
• A1C <7% (< 6% if can be achieved safely)
• Aim to achieve targets within 6-12 months
• Start with combination therapy or insulin for patients with A1C > 9%
• Consider insulin at any stage of treatment
• Vascular protection to further reduce cardiovascular risk
Key ChangesKey Changes
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Canadian Diabetes Association2003 Clinical Practice Guidelines
for the Prevention and Management of Diabetes in Canada
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 Goal in Type 2 Diabetes
Getting to Goal in Type 2 Diabetes
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Supplementary Slides:Key RecommendationsSupplementary 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].
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 1Recommendation 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 other classes 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/or additions of antihyperglycemic agents should be made in order to attain target A1C within 6 to 12 months [Grade D, Consensus].
If glycemic targets are not attained when a single antihyperglycemic agent is used initially, an antihyperglycemic agent or agents from other classes 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/or additions of antihyperglycemic agents should be made in order to attain target A1C within 6 to 12 months [Grade D, Consensus].
Recommendation 2Recommendation 2
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Recommendation 3Recommendation 3
This choice of antihyperglycemic agent(s) should take into 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 the information in Table 1 and Figure 1 [Grade D, Consensus for the order of antihyperglycemic agents listed in Figure 1].
This choice of antihyperglycemic agent(s) should take into 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 the information in Table 1 and Figure 1 [Grade D, Consensus for the order of antihyperglycemic agents listed in Figure 1].
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Recommendation 4Recommendation 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.
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 5Recommendation 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.)
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 6Recommendation 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].
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 7Recommendation 7
To safely achieve optimal postprandial glycemic control, mealtime insulin lispro or insulin aspart is preferred over regular insulin [Grade B, Level 2].
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 8Recommendation 8
When insulin given at night is added to oral antihyperglycemic agents, insulin glargine may be preferred over NPH to reduce overnight hypoglycemia [Grade B, Level 2] and weight gain [Grade B, Level 2 ].
When insulin given at night is added to oral antihyperglycemic agents, insulin glargine may be preferred over NPH to reduce overnight hypoglycemia [Grade B, Level 2] and weight gain [Grade B, Level 2 ].
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Recommendation 9Recommendation 9
All individuals with type 2 diabetes currently using or starting therapy with insulin or insulin secretagogues should be counselled about the recognition and prevention of drug-induced hypoglycemia [Grade D, Consensus].
All individuals with type 2 diabetes currently using or starting therapy with insulin or insulin secretagogues should be counselled about the recognition and prevention of drug-induced hypoglycemia [Grade D, Consensus].
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Supplementary Slides:Alternate Animation for
Treatment Algorithm
Supplementary Slides:Alternate Animation for
Treatment Algorithm
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Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight(BMI 25 kg/m2)
Non-overweight(BMI 25 kg/m2)
Biguanide alone or incombination with 1 of:
• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
1 or 2† antihyperglycemicagents from differentclasses
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Add a drug from a different class orUse insulin alone or in combination with:
• biguanide• insulin secretagogue• insulin sensitizer*• alpha-glucosidase inhibitor
Marked hyperglycemia (A1C 9.0%)
2 antihyperglycemic agentsfrom different classes †
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Basal and/orpreprandial insulin
Add an oral
antihyperglycemic agentfrom a differentclass or insulin*
Intensify insulinregimen or add
• biguanide• insulin secretagogue**• insulin sensitizer*• alpha-glucosidase inhibitor
If not at targetIf not at targetIf not at targetIf not at target
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
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Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight(BMI 25 kg/m2)
Biguanide alone or incombination with 1 of:
• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Add a drug from a different class orUse insulin alone or in combination with:
• biguanide• insulin secretagogue• insulin sensitizer*• alpha-glucosidase inhibitor
If not at target
Marked hyperglycemia (A1C 9.0%)
2 antihyperglycemic agentsfrom different classes †
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Basal and/orpreprandial insulin
Add an oral
antihyperglycemic agentfrom a differentclass or insulin*
If not at targetIf not at target
Intensify insulinregimen or add
• biguanide• insulin secretagogue**• insulin sensitizer*• alpha-glucosidase inhibitor
Non-overweight(BMI 25 kg/m2)
1 or 2† antihyperglycemicagents from differentclasses
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
If not at target
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
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S
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Y
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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
Overweight (BMI 25 kg/m2)
Mild to moderate hyperglycemia (A1C <9.0%)
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
Biguanide alone or in combination with 1 of:• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
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.
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Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight(BMI 25 kg/m2)
Non-overweight(BMI 25 kg/m2)
Biguanide alone or incombination with 1 of:
• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
1 or 2† antihyperglycemicagents from differentclasses
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Add a drug from a different class orUse insulin alone or in combination with:
• biguanide• insulin secretagogue• insulin sensitizer*• alpha-glucosidase inhibitor
Marked hyperglycemia (A1C 9.0%)
2 antihyperglycemic agentsfrom different classes †
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Basal and/orpreprandial insulin
Add an oral
antihyperglycemic agentfrom a differentclass or insulin*
Intensify insulinregimen or add
• biguanide• insulin secretagogue**• insulin sensitizer*• alpha-glucosidase inhibitor
If not at targetIf not at targetIf not at targetIf not at target
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
L
I
F
E
S
T
Y
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Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight(BMI 25 kg/m2)
Non-overweight(BMI 25 kg/m2)
Biguanide alone or incombination with 1 of:
• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
1 or 2† antihyperglycemicagents from differentclasses
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Add a drug from a different class orUse insulin alone or in combination with:
• biguanide• insulin secretagogue• insulin sensitizer*• alpha-glucosidase inhibitor
Marked hyperglycemia (A1C 9.0%)
2 antihyperglycemic agentsfrom different classes †
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Basal and/orpreprandial insulin
Add an oral
antihyperglycemic agentfrom a differentclass or insulin*
Intensify insulinregimen or add
• biguanide• insulin secretagogue**• insulin sensitizer*• alpha-glucosidase inhibitor
If not at targetIf not at targetIf not at targetIf not at target
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
L
I
F
E
S
T
Y
L
E
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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
Non-overweight (BMI 25 kg/m2)
Mild to moderate hyperglycemia (A1C <9.0%)
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
1 or 2† antihyperglycemic agents from different classes• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
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)
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Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight(BMI 25 kg/m2)
Non-overweight(BMI 25 kg/m2)
Biguanide alone or incombination with 1 of:
• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
1 or 2† antihyperglycemicagents from differentclasses
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Add a drug from a different class orUse insulin alone or in combination with:
• biguanide• insulin secretagogue• insulin sensitizer*• alpha-glucosidase inhibitor
Marked hyperglycemia (A1C 9.0%)
2 antihyperglycemic agentsfrom different classes †
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Basal and/orpreprandial insulin
Add an oral
antihyperglycemic agentfrom a differentclass or insulin*
Intensify insulinregimen or add
• biguanide• insulin secretagogue**• insulin sensitizer*• alpha-glucosidase inhibitor
If not at targetIf not at targetIf not at targetIf not at target
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
L
I
F
E
S
T
Y
L
E
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Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight(BMI 25 kg/m2)
Non-overweight(BMI 25 kg/m2)
Biguanide alone or incombination with 1 of:
• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
1 or 2† antihyperglycemicagents from differentclasses
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Add a drug from a different class orUse insulin alone or in combination with:
Marked hyperglycemia (A1C 9.0%)
2 antihyperglycemic agentsfrom different classes †
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Basal and/orpreprandial insulin
Add an oral
antihyperglycemic agentfrom a differentclass or insulin*
Intensify insulinregimen or add
• biguanide• insulin secretagogue**• insulin sensitizer*• alpha-glucosidase inhibitor
If not at targetIf not at targetIf not at targetIf not at target
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
• biguanide• insulin secretagogue• insulin sensitizer*• alpha-glucosidase inhibitor
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F
E
S
T
Y
L
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Add an oral antihyperglycemic agentfrom a different class or insulin*
Marked hyperglycemia (A1C 9.0%)
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
2 antihyperglycemic agents from different classes †
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
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
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Y
L
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Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight(BMI 25 kg/m2)
Non-overweight(BMI 25 kg/m2)
Biguanide alone or incombination with 1 of:
• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
1 or 2† antihyperglycemicagents from differentclasses
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Add a drug from a different class orUse insulin alone or in combination with:
• biguanide• insulin secretagogue• insulin sensitizer*• alpha-glucosidase inhibitor
Marked hyperglycemia (A1C 9.0%)
2 antihyperglycemic agentsfrom different classes †
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Basal and/orpreprandial insulin
Add an oral
antihyperglycemic agentfrom a differentclass or insulin*
Intensify insulinregimen or add
• biguanide• insulin secretagogue**• insulin sensitizer*• alpha-glucosidase inhibitor
If not at targetIf not at targetIf not at targetIf not at target
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
L
I
F
E
S
T
Y
L
E
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Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight(BMI 25 kg/m2)
Non-overweight(BMI 25 kg/m2)
Biguanide alone or incombination with 1 of:
• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
1 or 2† antihyperglycemicagents from differentclasses
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Add a drug from a different class orUse insulin alone or in combination with:
Marked hyperglycemia (A1C 9.0%)
2 antihyperglycemic agentsfrom different classes †
• biguanide• insulin sensitizer*• insulin secretagogue• insulin• alpha-glucosidase inhibitor
Basal and/orpreprandial insulin
Add an oral
antihyperglycemic agentfrom a differentclass or insulin*
Intensify insulinregimen or add
• biguanide• insulin secretagogue**• insulin sensitizer*• alpha-glucosidase inhibitor
If not at targetIf not at targetIf not at targetIf not at target
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
• biguanide• insulin secretagogue• insulin sensitizer*• alpha-glucosidase inhibitor
L
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F
E
S
T
Y
L
E
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Marked hyperglycemia (A1C 9.0%)
Timely adjustments to and/or additions of oral antihyperglycemic agentsand/or insulin should be made to attain target A1C within 6 to 12 months
Basal and/or preprandial insulin
If not at target
Intensify insulin regimen or add
• biguanide• insulin secretagogue**• insulin sensitizer*• alpha-glucosidase inhibitor
* 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.* * If using preprandial insulin, do not add an insulin secretagogue.
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