1. Canadian Diabetes Association Clinical Practice Guidelines Pharmacologic Management of Type 2 Diabetes Chapter 13 William Harper, Maureen Clement, Ronald Goldenberg, Amir Hanna, Andrea Main, Ravi Retnakaran, Diana Sherifali,Vincent Woo, Jean-François Yale

2. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Pharmacotherapy in T2DM Checklist CHOOSE initial therapy based on glycemia START with Metformin +/- others INDIVIDUALIZE your therapy choice based on characteristics of the patient and the agent REACH TARGET within 3-6 months of diagnosis 2013

3. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association GET TO TARGET WITHIN 3-6 MONTHS OF DIAGNOSIS 2013

4. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Initial Choice of Therapy Depends on Glycemia Initial A1C ≥8.5% Start metformin AND Consider combo therapy to achieve ≥1.5% A1C reduction Initial A1C <8.5% Start metformin OR Reassess in 2-3 months then decide on starting metformin 2013

5. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Initial Choice of Therapy Depends on Glycemia Symptomatic Hyperglycemia + Metabolic Decompensation INSULIN +/- Metformin Polyuria Polydipsia Weight loss Volume depletion Concern about Insulin Deficiency

6. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association What Comes After Metformin? Depends … Patient characteristicsAgent characteristics Degree of hyperglycemiaBG lowering efficacy & durability Risk of hypoglycemiaRisk of inducing hypoglycemia WeightEffect on weight Comorbidities (renal, cardiac, hepatic) Contraindications & side effects Access to treatmentCost and coverage Patient preferencesOther 2013

7. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

8. Start metformin immediately Consider initial combination with another antihyperglycemic agent Start lifestyle intervention (nutrition therapy and physical activity) +/- Metformin A1C <8.5% Symptomatic hyperglycemia with metabolic decompensation A1C  8.5% Initiate insulin +/- metformin If not at glycemic target (2-3 mos) Start / Increase metformin If not at glycemic targets LIFESTYLELIFESTYLE Add an agent best suited to the individual: Patient Characteristics Degree of hyperglycemia Risk of hypoglycemia Overweight or obesity Comorbidities (renal, cardiac, hepatic) Preferences & access to treatment Other See next page… AT DIAGNOSIS OF TYPE 2 DIABETES Agent Characteristics BG lowering efficacy and durability Risk of inducing hypoglycemia Effect on weight Contraindications & side-effects Cost and coverage Other 2013

9. If not at glycemic target From prior page… Add another agent from a different class Add/Intensify insulin regimen Make timely adjustments to attain target A1C within 3-6 months 2013 LIFESTYLELIFESTYLE

10. Start metformin immediately Consider initial combination with another antihyperglycemic agent Start lifestyle intervention (nutrition therapy and physical activity) +/- Metformin A1C < 8.5% Symptomatic hyperglycemia with metabolic decompensation A1C  8.5% Initiate insulin +/- metformin If not at glycemic target (2-3 mos) Start / Increase metformin If not at glycemic targets LIFESTYLELIFESTYLE Add an agent best suited to the individual: Patient Characteristics Degree of hyperglycemia Risk of hypoglycemia Overweight or obesity Comorbidities (renal, cardiac, hepatic) Preferences & access to treatment Other See next page… AT DIAGNOSIS OF TYPE 2 DIABETES Agent Characteristics BG lowering efficacy and durability Risk of inducing hypoglycemia Effect on weight Contraindications & side-effects Cost and coverage Other 2013

11. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

12. Types of Insulin

13. Types of Insulin (continued)

14. Serum Insulin Level Time Analogue Bolus: Apidra, Humalog, NovoRapid Human Basal: Humulin-N, Novolin ge NPH Analogue Basal: Lantus, Levemir Human Bolus: Humulin-R, Novolin ge Toronto guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

15. Time Serum Insulin Level Human Premixed : Humulin 30/70, Novolin ge 30/70 Analogue Premixed: Humalog Mix25, NovoMix 30 guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

16. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

17. Adapted from: Product Monographs as of March 1, 2013; CDA Guidelines 2008; and Yale JF. J Am Soc Nephrol 2005; 16:S7-S10. Antihyperglycemic Agents and Renal Function Not recommended / contraindicated Safe Caution and/or dose reduction Repaglinide Metformin 30 60 Saxagliptin Linagliptin Glyburide 30 50 Thiazolidinediones 30 GFR (mL/min): < 15 15-29 30-59 60-89 ≥ 90 CKD Stage: 5 4 3 2 1 Gliclazide/Glimepiride 15 30 Liraglutide 50 Exenatide 30 50 Acarbose 25 Sitagliptin 50 15 2.5 mg 15 30 50 mg 25 mg guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association

18. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 1.In people with type 2 diabetes, if glycemic targets are not achieved using lifestyle management within 2-3 months, antihyperglycemic agent therapy should be initiated [Grade A, level 1] Recommendation 1 Metformin may be used at time of diagnosis, in conjunction with lifestyle management [Grade D, consensus] 2013

19. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 1.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] Individuals with symptomatic hyperglycemia and metabolic decompensation should receive an initial antihyperglycemic regimen containing insulin [Grade D, Consensus] 2013 Recommendation 1 (continued)

20. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 2 2.Metformin should be the initial drug used [(Grade A, Level 1) for overweight patients; (Grade D, consensus) for non-overweight patients]

21. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 3 3.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 3-6 months [Grade D, consensus] 2013

22. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 4.Choice of pharmacological agents should be individualized taking into consideration [Grade D, consensus] Patient Characteristics Degree of hyperglycemia Presence of co-morbidities Patient preference Ability to access treatments Properties of the Treatment Effectiveness and durability of lowering BG Risk of hypoglycemia Effectiveness in reducing complications Effect on body weight Side effects Contraindications Recommendation 4

23. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 5.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] Recommendation 5

24. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association Recommendation 6 6.When bolus insulin is added to antihyperglycemic agents, rapid-acting analogues (insulin aspart, glulisine, or lispro) may be used instead of regular insulin to reduce the risk of hypoglycemia [Grade A, Level 1A]

25. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association 7.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] Recommendation 7

26. guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.ca Copyright © 2013 Canadian Diabetes Association CDA Clinical Practice Guidelines http://guidelines.diabetes.cahttp://guidelines.diabetes.ca – for professionals 1-800-BANTING (226-8464) http://diabetes.ca http://diabetes.ca – for patients