2008 Clinical Practice Guidelines - Canadian Diabetes Association

smaller underpowered studies suggested possible cardiovascular
harm specific to TZD use (54,55) this has not been
demonstrated in larger randomized clinical trials (56-58).
In patients for whom hypoglycemia is a particular concern,
agents associated with less hypoglycemia are preferred.Table 1
and Figure 1 provide information to aid decision-making.
A combination of oral antihyperglycemic agents and
insulin often effectively controls glucose levels.When insulin
is added to oral antihyperglycemic agent(s), a single injection
of intermediate-acting (NPH) (6,59), or an extended longacting
insulin analogue (insulin glargine or insulin detemir)
(19) may be added. This approach may result in better
glycemic control with a smaller dose of insulin (60) and may
induce less weight gain and less hypoglycemia than that seen
when oral agents are stopped and insulin is used alone (33).
The addition of bedtime insulin to metformin therapy leads
to less weight gain than insulin plus a sulfonylurea or twicedaily
NPH insulin (16).While combining insulin with a TZD
is not an approved indication in Canada, the addition of such
agents to insulin in carefully selected patients improves
glycemic control and reduces insulin requirements (61).
Such combination can result in increased weight, fluid retention
and, in few patients, CHF. Inhaled insulin (approved, but
not yet available in Canada) can also be added to oral antihyperglycemic
therapy to help control BG levels, but can cause
RECOMMENDATIONS
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 (3)]. In the presence of marked hyperglycemia (A1C
≥9.0%), antihyperglycemic agents should be initiated concomitantly
with lifestyle management, and consideration
should be given to initiating combination therapy with 2
agents or initiating insulin treatment in symptomatic individuals
[Grade D, Consensus].
2. If glycemic targets are not attained when a single antihyperglycemic
agent is used initially, an antihyperglycemic
agent or agents from different classes should be added.
The lag period before adding other agent(s) should be
kept to a minimum, taking into account the characteristics
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].
3. Pharmacological treatment regimens should be individualized
taking into consideration the degree of hyperglycemia
and the properties of the antihyperglycemic agents including:
effectiveness in lowering BG, durability of glycemic
control, side effects, contraindications, risk of hypoglycemia,
presence of diabetes complications or comorbidities,
and patient preferences [Grade D, Consensus].
The following factors and the information shown in
Table 1 and Figure 1 should also be taken into account:
• Metformin should be the initial drug used in both overweight
patients [Grade A, Level 1A (52)] and nonover-
cough and slight reductions in pulmonary function tests (62).
The use of inhaled insulin should be restricted to nonsmokers
and those without respiratory disorders. Pulmonary
function tests should be done at baseline, 6 months and annually
during inhaled insulin therapy.
Insulin can be used at diagnosis in individuals with marked
hyperglycemia and can be used temporarily during illness,
pregnancy, stress, or for a medical procedure or surgery.There
is no evidence that exogenous insulin accelerates the risk of
macrovascular complications of diabetes, and its appropriate
use should be encouraged (63).When insulin is used in type 2
diabetes, the insulin regimen should be tailored to achieve good
metabolic control while trying to avoid severe hypoglycemia.
With intensive glycemic control, there is an increased risk of
hypoglycemia, but this risk is lower in people with type 2 diabetes
than in those with type 1 diabetes.The number of insulin
injections (1–4 per day) and the timing of injections may vary
depending on each individual’s situation (64).The reduction in
A1C achieved with insulin therapy depends on the dose and
number of injections per day of insulin.
As type 2 diabetes progresses, insulin doses will likely need
to be increased, additional doses of basal insulin (intermediateacting
or long-acting analogues) may need to be added, and
prandial insulin (short-acting or rapid-acting analogues or
inhaled insulin) may also be required.
weight patients [Grade D, Consensus].
• Other classes of antihyperglycemic agents, including
insulin, should be added to metformin, or used in combination
with each other, if glycemic targets
are not met, taking into account the information
in Figure 1 and Table 1 [Grade D, Consensus].
4. When basal insulin is added to antihyperglycemic
agents, long-acting analogues (insulin detemir or insulin
glargine) may be considered instead of NPH to reduce
the risk of nocturnal and symptomatic hypoglycemia
[Grade A, Level 1A (71)].
5. The following antihyperglycemic agents (listed in alphabetical
order), should be considered to lower postprandial
BG levels:
• Alpha-glucosidase inhibitor [Grade B, Level 2 (10)]
• Premixed insulin analogues (i.e. biphasic insulin aspart
and insulin lispro/protamine) instead of regular/
NPH premixtures [Grade B, Level 2 (72,73)]
• DPP-4 inhibitor [Grade A, Level 1 (13,14,74)].
• Inhaled insulin [Grade B, Level 2 (20)].
• Meglitinides (repaglinide, nateglinide) instead of
sulfonylureas [Grade B, Level 2 (75,76)]
• Rapid-acting insulin analogues (aspart, glulisine, lispro)
instead of short-acting insulin (i.e. regular insulin) [Grade
B, Level 2 (21,77,78)].
6. 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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MANAGEMENT