<strong>2008</strong> CLINICAL PRACTICE GUIDELINES S56 Figure 1. Management of hyperglycemia in type 2 diabetes L I F E S T Y L E Initiate metformin A1C = glycated hemoglobin BP = blood pressure CHF = congestive heart failure A1C
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]. S57 MANAGEMENT
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