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PHARMACOLOGIC MANAGEMENT OF TYPE 2 DIABETES

PHARMACOLOGIC MANAGEMENT OF TYPE 2 DIABETES. 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. PHARMACOLOGIC MANAGEMENT.

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PHARMACOLOGIC MANAGEMENT OF TYPE 2 DIABETES

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  1. PHARMACOLOGIC MANAGEMENTOF TYPE 2 DIABETES 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada

  2. PHARMACOLOGIC MANAGEMENT • The stepwise approach described in the 1998 CDA Clinical Practice Guidelines implied that it was acceptable to wait for up to 8 to 16 months before implementing aggressive therapy to treat hyperglycemia. • It is now recommended that the management regimens of patients with type 2 diabetes be tailored to the individual patient, aiming for glycemic targets as close to normal as possible and, in most people, as early as possible. • Multiple therapies may be required to achieve optimal glycemic control in type 2 diabetes. • The choice of antihyperglycemic agent(s) should be based on the individual patient. • Target A1C should be attainable within 6 to 12 months.

  3. PHARMACOLOGIC MANAGEMENT • A combination of oral agents and insulin often effectively control glucose levels in people with type 2 diabetes. • Insulin therapy, without concomitant use of oral agents, is generally used when other modalities have failed or are contraindicated. • However, insulin may be used as initial therapy, especially in he presence of marked hyperglycemia (A1C 9%). • There is no evidence that exogenous insulin accelerates the risk of macrovascular complications of diabetes and its appropriate use should be encouraged. • It is important to prevent, recognize and treat hypoglycemic episodes secondary to the use of insulin or insulin secretagogues.

  4. MANAGEMENT OF HYPERGLYCEMIA IN TYPE 2 DIABETES Clinical assessment and initiation of nutrition therapy and physical activity Mild to moderate hyperglycemia (A1C < 9%) Marked hyperglycemia (A1C > 9%) LIFESTYLE - continued on next slide -

  5. MANAGEMENT OF HYPERGLYCEMIA IN TYPE 2 DIABETES - cont’d Mild to moderate hyperglycemia (A1C < 9%) Overweight (BMI 25) Non-overweight (BMI < 25) Metformin alone or in combination with one of: - insulin sensitizer (TZD) - insulin secretagogue - insulin - acarbose One or two agents from different classes: - metformin - insulin sensitizer (TZD) - insulin secretagogue - insulin - acarbose LIFESTYLE If not at target If not at target Add a drug from a different class OR use insulin alone or in combination with: - metformin - insulin secretagogue - insulin sensitizer - acarbose

  6. MANAGEMENT OF HYPERGLYCEMIA IN TYPE 2 DIABETES - cont’d Marked hyperglycemia (A1C  9%) 2 agents from different classes: - metformin - insulin sensitizer (TZD) - insulin secretatogue - insulin - acarbose Basal and/or preprandial insulin LIFESTYLE If not at target If not at target Intensify insulin regimen or add: - metformin - insulin secretagogue - insulin sensitizer (TZD) - acarbose Add an oral agent from a different class or insulin

  7. KEY CLINICAL NOTES • When used in combination, insulin and TZDs may increase the risk of edema or CHF. The combination of a TZD and insulin is currently not an approved indication in Canada. • If on preprandial insulin, do not add an insulin secretagogue. • Hypoglycemia can occur with insulin and insulin secretagogues (more with glyburide than other secretagogues). • Edema and fluid retention can occur with TZDs and rarely with insulin. • Moderate weight gain can occur with insulin, insulin secretagogues or TZDs. • Metformin can have GI side effects.

  8. KEY CONTRAINDICATIONS • Liver disease - glyburide, metformin, TZDs • Significant renal insufficiency - metformin, sulfonylureas • Significant cardiac failure - metformin, TZDs • Sulfa allergy - sulfonylureas

  9. GENERIC & TRADE NAMES OF ORAL ANTIHYPERGLYCEMIC MEDICATIONS

  10. ANTIHYPERGLYCEMIC AGENTS CLASS: alpha-glucosidase inhibitor Agent: acarbose Expected decrease in A1C with monotherapy: 0.5-0.8% Therapeutic considerations: • not recommended as initial therapy in people with severe hyperglycemia (A1C  9%) • used mostly in combination with other oral agents • GI side effects • treat hypoglycemia with dextrose tablets, milk or honey

  11. ANTIHYPERGLYCEMIC AGENTS CLASS: biguanide Agent: metformin Expected decrease in A1C with monotherapy: 1.0-1.5% Therapeutic considerations: • contraindicated in patients with renal or hepatic dysfunction or cardiac failure • use Cockcroft-Gault formula to calculate creatinine clearance; < 60 mL/min indicates use with caution or contraindicates use of metformin • GI side effects • less weight gain than sulfonylureas • does not cause hypoglycemia

  12. ANTIHYPERGLYCEMIC AGENTS CLASS: insulin Expected decrease in A1C with monotherapy: depends on regimen Therapeutic considerations: • when initiating, consider adding bedtime intermediate- or long-acting insulin or extended long-acting analogue to daytime oral agents • causes greatest fall in A1C and has no maximal dose • is associated with increased risk of weight gain relative to sulfonylureas and metformin

  13. ANTIHYPERGLYCEMIC AGENTS CLASS: insulin secretagogues Agents: sulfonylurea (gliclazide, glimepiride, glyburide) non-sulfonylurea (nateglinide, repaglinide) Expected decrease in A1C with monotherapy: 1.0-1.5% (0.5% for nateglinide) Therapeutic considerations: • All reduce A1C comparably, except nateglinide • Postprandial glycemia is especially reduced by nateglinide and repaglinide • Hypoglycemia and weight gain are more common with glyburide

  14. ANTIHYPERGLYCEMIC AGENTS CLASS: insulin sensitizers (thiazolidinediones, TZDs) Agents: pioglitazone, rosiglitazone Expected decrease in A1C with monotherapy: 1.0-1.5% Therapeutic considerations: • contraindicated in patients with hepatic dysfunction (hepatic enzymes > 2.5 x upper limit of normal) or significant cardiac dysfunction • need 6 to 12 weeks to achieve full glucose-lowering effect • may induce edema, fluid retention, weight gain • can combine with sulfonylurea and/or metformin

  15. ANTIHYPERGLYCEMIC AGENTS CLASS: anti-obesity agent Agent: orlistat Expected decrease in A1C with monotherapy: 0.5% Therapeutic considerations: • associated with weight loss • GI side effects • effect on glycemia probably indirect

  16. PHARMA. MGMT. OF TYPE 2 DM- RECOMMENDATIONS • 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].

  17. PHARMA. MGMT. OF TYPE 2 DM- RECOMMENDATIONS • 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].

  18. PHARMA. MGMT. OF TYPE 2 DM- RECOMMENDATIONS • The 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 agents listed in the Management of Hyperglycemia figure].

  19. PHARMA. MGMT. OF TYPE 2 DM- RECOMMENDATIONS • 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.

  20. PHARMA. MGMT. OF TYPE 2 DM- RECOMMENDATIONS • 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.)

  21. PHARMA. MGMT. OF TYPE 2 DM- RECOMMENDATIONS • 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]. • To safely achieve optimal postprandial glycemic control, mealtime insulin lispro or insulin aspart is preferred over regular insulin [Grade B, Level 2].

  22. PHARMA. MGMT. OF TYPE 2 DM- RECOMMENDATIONS • 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]. • 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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