Download Document

Canadian Diabetes Association
2003 Clinical Practice Guidelines
for the Prevention and Management
of Diabetes in Canada
Getting to Goal
in Type 2 Diabetes
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.
Many patients have inadequate glycemic control
100
100
80
60
US (1988-1994)2
50%
50%
40
20
Percentage of subjects
Percentage of subjects
CAN (2003)1
0
 7%
A1C (%)
2 Harris
62%
60
40
38%
20
0
< 7%
1 Harris
80
S, et al, The Diabetes in Canada Evaluation (DICE) Study, ADA 2003, 2162-PO
MI, et al. Diabetes Care 1999; 22:403–408.
<7%
> 7%
A1C (%)
Proportion of patients with A1C > 7.0
increases with duration of type 2 diabetes
67%
62%
53%
42%
31%
<=2
3-5
6-9
10-14
15+
Years T2DM
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.
Proportion of patients with hypertension
increases with duration of type 2 diabetes
71%
72%
10-14
15+
64%
57%
53%
<=2
3-5
6-9
Years T2DM
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.
Proportion of patients with dyslipidemia
increases with duration of type 2 diabetes
66%
55%
<=2
57%
58%
59%
3-5
6-9
10-14
15+
Years T2DM
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.
Proportion of patients with cardiovascular disease
increases with duration of type 2 diabetes
48%
29%
21%
24%
15%
<=2
3-5
6-9
10-14
15+
Years T2DM
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.
Proportion of patients with microvascular disease
increases with duration of type 2 diabetes
62%
42%
44%
6-9
10-14
32%
21%
<=2
3-5
15+
Years T2DM
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.
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
UKPDS: decreased risk of diabetes-related complications
associated with a 1% decrease in A1C
Percentage decrease in relative risk
corresponding to a 1% decrease in HbA1C
Observational analysis from UKPDS study data
Any
diabetesrelated
endpoint
Diabetesrelated
death
21%
21%
**
**
All
Myocardial
cause
mortality infarction
14%
14%
**
**
Stroke
Peripheral
vascular
disease†
Microvascular
disease
12%
*
19%
**
37%
†Lower
extremity amputation or fatal peripheral vascular disease
*P = 0.035; **P < 0.0001
43%
**
**
Adapted from Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405–412.
Cataract
extraction
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
Stratton IM, et al. UKPDS 35. BMJ 2000; 321:405–412.
UKPDS demonstrated loss of glycemic
control with all agents studied
A1C (%)
9
8
Conventional
Glyburide
Chlorpropamide
Metformin
Insulin
7
Upper limit of of normal = 6.2%
6
0
0
2
4
6
8
Years from randomization
UK Prospective Diabetes Study Group. UKPDS 34. Lancet 1998; 352:854–865.
10
Overweight patients
Cohort, median values
Proportion of patients with A1C < 7.0% on
monotherapy at 3, 6 and 9 years
Overweight patients
Proportion of patients (%)
100
Diet
Insulin
Sulfonylurea
Metformin
80
60
50%
40
20
0
3
6
9
3
6
9
3
6
Years from randomization
Turner RC, et al. UKPDS 49. JAMA 1999; 281:2005–2012.
9
3
6
9
Error bars = 95% CI
The UKPDS demonstrated progressive
decline of -cell function over time
-cell function (%)
100
Start of treatment
80
60
40
20
P < 0.0001
0
–10 –9 –8 –7 –6 –5 –4 –3 –2 –1
1
2
3
4
5
6
Time from diagnosis (years)
HOMA model, diet-treated n = 376
Adapted from Holman RR. Diabetes Res Clin Pract 1998; 40 (Suppl.):S21–S25.
Canadian Diabetes Association
2003 Clinical Practice Guidelines
for the Prevention and Management
of Diabetes in Canada
Glycemic Targets
1998 CDA Treatment Targets
Level
†
Ideal
Optimal*
Suboptimal
(normal
nondiabetic)
(target goal)
(action may
be required)
(action
required)
<100
(.04-.06)
<115
(<0.07)
116-140
(.07-8.4)
>140
(>0.084)
Fasting or
premeal glucose
level (mmol/L)
3.8-6.1
4-7
7.1-10
>10
Glucose level
1-2 h after meal
(mmol/L)
4.4-7
5.0-11
11.1-14
>14
Glycated Hb
(% of upper
limit)
e.g., HbA1c
assay
Inadequate
‡
CMAJ 1998; 159 (8 Suppl):S1-29
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
2003 CDA Recommended Targets for
Glycemic Control
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 be
achieved 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
Components of Glycemic Control
A1C
<7%, <6%*
Fasting/Preprandial
Plasma Glucose
2 h. Postprandial
Plasma Glucose
4-7 mmol/L
4-6 mmol/L*
5-10 mmol/L
5-8 mmol/L*
*If can be achieved safely
Canadian Diabetes Association
2003 Clinical Practice Guidelines
for the Prevention and Management
of Diabetes in Canada
Management of Hyperglycemia
in Type 2 Diabetes
Lifestyle 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.
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 <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
Antihyperglycemic Agents
Primary Sites of Action of Oral
Antihyperglycemic Agents
-glucosidase inhibitors
Stomach
Carbohydrate
Gut
Insulin
secretagogues
Glucose (G)
I
I
Adipose tissue
Insulin
Pancreas
I
Liver
Biguanides
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.
Muscle
Thiazolidinediones
Key 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
New Treatment Options for
Type 2 Diabetes
Stepwise treatment
Diet/
exercise
Oral
Oral
monotherapy combination
Early aggressive
combination therapy as required
Oral
+/- insulin
Insulin
Management of Hyperglycemia in
Type 2 Diabetes
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)
Marked hyperglycemia (A1C 9.0%)
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight (BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase inhibitor
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in combination with 1 of:
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
* 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.
Dose-Effect Relationship
Maximal
Effect
Therapeutic effect
Half-maximal
Side effect
Half-maximal
Maximal
Dose
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.
Riddle M. Combiningsulfonylureas and other oral agents.Am J of Med. 2000; 108(6A):15S-22S.
Dose-Response Curve
1.5
1.0
30
20
0.5
10
0
0
500
1000
1500
2000
2500
Dose
Dose-response curve showing GI related effects
Riddle M. Combiningsulfonylureas and other oral agents.Am J of Med. 2000; 108(6A):15S-22S.
GI Distress Patients (%)
Reduction vs. placebo, HbA1c (%)
2.0
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight (BMI 25 kg/m2)
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase inhibitor
L
I
F
E
S
T
Y
L
E
1 or 2† antihyperglycemic agents from different classes
If not at target
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
* 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)
Marked hyperglycemia (A1C 9.0%)
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase inhibitor
If not at target
L
I
F
E
S
T
Y
L
E
2 antihyperglycemic agents from different classes †
Add an oral antihyperglycemic agent
from a different class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
* 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)
Marked hyperglycemia (A1C 9.0%)
L
E
Basal and/or preprandial insulin
L
I
F
E
S
T
Y
If not at target
Intensify insulin regimen or add
• biguanide
• insulin secretagogue**
• insulin sensitizer*
• alpha-glucosidase inhibitor
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
* 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.
Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight
(BMI 25 kg/m2)
Overweight
(BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
1 or 2† antihyperglycemic
agents from different
classes
2 antihyperglycemic agents
from different classes †
Basal and/or
preprandial insulin
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
If not at target
If not at target
If not at target
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in
combination with 1 of:
Marked hyperglycemia (A1C 9.0%)
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Add an oral
antihyperglycemic agent
from a different
class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
Intensify insulin
regimen or add
• biguanide
• insulin
secretagogue**
• insulin sensitizer*
• alpha-glucosidase
inhibitor
Key Changes
•
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
Canadian Diabetes Association
2003 Clinical Practice Guidelines
for the Prevention and Management
of Diabetes in Canada
Getting to Goal
in Type 2 Diabetes
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.
Supplementary Slides:
Key Recommendations
Recommendation 1
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 2
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 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].
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.
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.)
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].
Recommendation 7
To safely achieve optimal postprandial glycemic
control, mealtime insulin lispro or insulin aspart is
preferred over regular insulin [Grade B, Level 2].
Recommendation 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 ].
Recommendation 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].
Supplementary Slides:
Alternate Animation for
Treatment Algorithm
Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight
(BMI 25 kg/m2)
Overweight
(BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
1 or 2† antihyperglycemic
agents from different
classes
2 antihyperglycemic agents
from different classes †
Basal and/or
preprandial insulin
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
If not at target
If not at target
If not at target
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in
combination with 1 of:
Marked hyperglycemia (A1C 9.0%)
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Add an oral
antihyperglycemic agent
from a different
class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
Intensify insulin
regimen or add
• biguanide
• insulin
secretagogue**
• insulin sensitizer*
• alpha-glucosidase
inhibitor
Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight
(BMI 25 kg/m2)
Overweight
(BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
1 or 2† antihyperglycemic
agents from different
classes
2 antihyperglycemic agents
from different classes †
Basal and/or
preprandial insulin
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
If not at target
If not at target
If not at target
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in
combination with 1 of:
Marked hyperglycemia (A1C 9.0%)
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Add an oral
antihyperglycemic agent
from a different
class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
Intensify insulin
regimen or add
• biguanide
• insulin
secretagogue**
• insulin sensitizer*
• alpha-glucosidase
inhibitor
Mild to moderate hyperglycemia (A1C <9.0%)
Overweight (BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase inhibitor
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in combination with 1 of:
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
* 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.
Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight
(BMI 25 kg/m2)
Overweight
(BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
1 or 2† antihyperglycemic
agents from different
classes
2 antihyperglycemic agents
from different classes †
Basal and/or
preprandial insulin
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
If not at target
If not at target
If not at target
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in
combination with 1 of:
Marked hyperglycemia (A1C 9.0%)
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Add an oral
antihyperglycemic agent
from a different
class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
Intensify insulin
regimen or add
• biguanide
• insulin
secretagogue**
• insulin sensitizer*
• alpha-glucosidase
inhibitor
Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight
(BMI 25 kg/m2)
Overweight
(BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
1 or 2† antihyperglycemic
agents from different
classes
2 antihyperglycemic agents
from different classes †
Basal and/or
preprandial insulin
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
If not at target
If not at target
If not at target
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in
combination with 1 of:
Marked hyperglycemia (A1C 9.0%)
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Add an oral
antihyperglycemic agent
from a different
class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
Intensify insulin
regimen or add
• biguanide
• insulin
secretagogue**
• insulin sensitizer*
• alpha-glucosidase
inhibitor
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight (BMI 25 kg/m2)
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase inhibitor
L
I
F
E
S
T
Y
L
E
1 or 2† antihyperglycemic agents from different classes
If not at target
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
* 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)
Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight
(BMI 25 kg/m2)
Overweight
(BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
1 or 2† antihyperglycemic
agents from different
classes
2 antihyperglycemic agents
from different classes †
Basal and/or
preprandial insulin
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
If not at target
If not at target
If not at target
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in
combination with 1 of:
Marked hyperglycemia (A1C 9.0%)
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Add an oral
antihyperglycemic agent
from a different
class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
Intensify insulin
regimen or add
• biguanide
• insulin
secretagogue**
• insulin sensitizer*
• alpha-glucosidase
inhibitor
Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight
(BMI 25 kg/m2)
Overweight
(BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
1 or 2† antihyperglycemic
agents from different
classes
2 antihyperglycemic agents
from different classes †
Basal and/or
preprandial insulin
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
If not at target
If not at target
If not at target
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in
combination with 1 of:
Marked hyperglycemia (A1C 9.0%)
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Add an oral
antihyperglycemic agent
from a different
class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
Intensify insulin
regimen or add
• biguanide
• insulin
secretagogue**
• insulin sensitizer*
• alpha-glucosidase
inhibitor
Marked hyperglycemia (A1C 9.0%)
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase inhibitor
If not at target
L
I
F
E
S
T
Y
L
E
2 antihyperglycemic agents from different classes †
Add an oral antihyperglycemic agent
from a different class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
* 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)
Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight
(BMI 25 kg/m2)
Overweight
(BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
1 or 2† antihyperglycemic
agents from different
classes
2 antihyperglycemic agents
from different classes †
Basal and/or
preprandial insulin
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
If not at target
If not at target
If not at target
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in
combination with 1 of:
Marked hyperglycemia (A1C 9.0%)
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Add an oral
antihyperglycemic agent
from a different
class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
Intensify insulin
regimen or add
• biguanide
• insulin
secretagogue**
• insulin sensitizer*
• alpha-glucosidase
inhibitor
Clinical assessment and initiation of nutrition and physical activity
Mild to moderate hyperglycemia (A1C <9.0%)
Non-overweight
(BMI 25 kg/m2)
Overweight
(BMI 25 kg/m2)
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
1 or 2† antihyperglycemic
agents from different
classes
2 antihyperglycemic agents
from different classes †
Basal and/or
preprandial insulin
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
• biguanide
• insulin sensitizer*
• insulin secretagogue
• insulin
• alpha-glucosidase
inhibitor
If not at target
If not at target
If not at target
If not at target
L
I
F
E
S
T
Y
L
E
Biguanide alone or in
combination with 1 of:
Marked hyperglycemia (A1C 9.0%)
Add a drug from a different class
or
Use insulin alone or in combination with:
• biguanide
• insulin secretagogue
• insulin sensitizer*
• alpha-glucosidase inhibitor
Add an oral
antihyperglycemic agent
from a different
class or insulin*
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
Intensify insulin
regimen or add
• biguanide
• insulin
secretagogue**
• insulin sensitizer*
• alpha-glucosidase
inhibitor
Marked hyperglycemia (A1C 9.0%)
L
E
Basal and/or preprandial insulin
Intensify insulin regimen or add
L
I
F
E
S
T
Y
If not at target
• biguanide
• insulin secretagogue**
• insulin sensitizer*
• alpha-glucosidase inhibitor
Timely adjustments to and/or additions of oral antihyperglycemic agents
and/or insulin should be made to attain target A1C within 6 to 12 months
* 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.