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Canadian Pharmacists Association
Canadian Pharmacists Association
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Chapter 13: Pharmacologic Management of Type 2 Diabetes

Canadian Diabetes Association 2013 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada

  

Introduction
  • Treatment regimens and therapeutic targets should be individualized for patients with type 2 diabetes.
  • Lifestyle modification, including nutritional therapy and physical activity, should continue to be emphasized while pharmacotherapy is being used as many agent classes can cause weight gain as a side effect.
Treatment Regimens
  • In people with type 2 diabetes, if glycemic targets are not achieved using lifestyle management within 2 to 3 months, antihyperglycemic agent therapy should be initiated [Grade A, Level 1A].

  • If A1C ≥8.5%, antihyperglycemic agents should be initiated concomitantly with lifestyle management, and consideration should be given to initiating combination therapy with 2 agents, one of which may be insulin [Grade D, Consensus].

  • With timely adjustments to and/or additions of antihyperglycemic agents, the target A1C level should be attainable within 3 to 6 months.

  • The initial use of combinations of submaximal doses of antihyperglycemic agents produces more rapid and improved glycemic control and fewer side effects compared to monotherapy at maximal doses

    • Many patients on monotherapy with the late addition of another antihyperglycemic agent may not readily attain target blood glucose (BG) levels.

  • When combining antihyperglycemic agents with or without insulin, classes of agents that have different mechanisms of action should be used.

  • There is debate over which antihyperglycemic agent (including insulin) should be used initially and which agents should be added subsequently. There is also debate over which agents within a given class might be preferred in specific situations.

  • Metformin may be used at the time of diagnosis, in conjunction with lifestyle management [Grade D, Consensus].  Metformin should be the initial drug used [Grade A, Level 1A for overweight patients; Grade D, Consensus for non-overweight patients].

    • Metformin is recommended based on its effectiveness in lowering BG, its relatively mild side effect profile, its long-term safety track record, its negligible risk of hypoglycemia and low risk of weight gain.

  • While monotherapy with the thiazolidinedione (TZD) rosiglitazone produces more long-lasting glycemic control compared to metformin or glyburide therapy, the adverse side effects and cardiovascular risks significantly limit the clinical utility of this drug class.

    • Although meta-analyses of smaller, underpowered studies suggested possible risk of MI with rosiglitazone, this has not been demonstrated in a larger randomized clinical trial.

    • Conversely, the evidence for pioglitazone suggests a possible reduced risk of cardiovascular events, although heart failure and increased fractures are still concerning side effects.

  • 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], and these adjustments to and/or additions of antihyperglycemic agents should be made in order to attain target A1C within 3 to 6 months [Grade D, Consensus].

  • Choice of pharmacological treatment agents should be individualized, taking into consideration [Grade D, Consensus]:

    • Patient characteristics: Degree of hyperglycemia, presence of comorbidities, patient preference and ability to access treatments.

    • Properties of the treatment: Effectiveness and durability of lowering BG, risk of hypoglycemia, effectiveness in reducing diabetes complications, effect on body weight, side effects, contraindications.

  • A combination of oral antihyperglycemic agents and insulin often effectively controls glucose levels. When bolus insulin is added to antihyperglycemic agents, rapid-acting analogues may be used instead of regular insulin to improve glycemic control [Grade B, Level 2] and to reduce the risk of hypoglycemia [Grade D, Consensus].

    • 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.

  • Individuals with symptomatic hyperglycemia and metabolic decompensation should receive an initial antihyperglycemic regimen containing insulin [Grade D, Consensus].

  • Insulin can be used at diagnosis in individuals with marked hyperglycemia and can also 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.

  • When insulin is used in type 2 diabetes, the insulin regimen should be tailored to achieve good metabolic control while trying to avoid excessive hypoglycemia.

    • The number of insulin injections (1 to 4 per day) and the timing of injections may vary, depending on each individual's situation.

    • The reduction in A1C achieved with insulin therapy depends on the dose and number of injections per day.

    • Insulin regimens based on basal or bolus insulin appear to be equally effective and superior with respect to glycemic lowering compared to biphasic insulin-based regimens.

  • As type 2 diabetes progresses, insulin requirements will likely increase, additional doses of basal insulin (intermediate-acting or long-acting analogues) may need to be added and bolus insulin (short-acting or rapid-acting analogues) may also be required.

    • Generally, once bolus insulin is introduced into a treatment regimen, either as a separate meal time bolus or as part of a premixed containing regimen, insulin secretagogues, such as sulfonylureas and meglitinides, are usually discontinued.

    • Concomitant metformin therapy, unless contraindicated, should be continued with regimens containing bolus insulin, including intensive basal-bolus regimen, to allow for improved glycemic control with less risk of weight gain and hypoglycemia.

FIGURE 1

TABLE 1

FIGURE 2

Hypoglycemia
  • Medication-induced hypoglycemia is the most common cause of hypoglycemia and occurs annually in up to approximately 20% of patients taking insulin secretagogues.
  • All individuals with type 2 diabetes currently using or starting therapy with insulin or insulin secretagogues should be counseled about the prevention, recognition and treatment of drug-induced hypoglycemia [Grade D, Consensus].
  • When basal insulin is added to antihyperglycemic agents, long-acting analogues (detemir or glargine) may be used instead of intermediate-acting NPH to reduce the risk of nocturnal and symptomatic hypoglycemia [Grade A, Level 1A].
Health care provider tools (from CDA)

Blood Glucose-Lowering Therapies – Quick reference guide.

Pharmacotherapy for Type 2 Diabetes – Decision-support tool based on patient characteristics.

For definitions of the levels of evidence cited in this chapter, please refer to the Guideline Recommendations: Levels of Evidence.

If you would like more details on this topic, please visit the Canadian Diabetes Association Clinical Practice Guidelines: Chapter 13. For a cost reference list of commonly prescribed antihyperglycemics, see Appendix 5. For examples of insulin initiation and titration regimens for type 2 diabetes, see Appendix 3.