Canadian Diabetes Association 2013 Clinical Practice Guidelines

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1 Canadian Diabetes Association 2013 Clinical Practice Guidelines The Essentials (Updated d November 2016)

2 Faculty/Presenter Disclosure Faculty: Alan Bell MD CCFP Relationships with commercial and non-commercial interests: Grants/Research Support: Amgen, Bristol Myers Squibb, Janssen, Takeda, AstraZeneca, Novartis, Pfizer, Bayer, Lilly, Boehringer Ingelheim, Sanofi, Valeant Speakers Bureau/Honoraria: Tweed, Amgen, Bristol Myers Squibb, Janssen, Takeda, AstraZeneca, Novartis, Pfizer, Bayer, Lilly, Boehringer Ingelheim, Sanofi, Valeant Consulting Fees: Tweed, Amgen, Bi Bristol lmyers Squibb, Janssen, Takeda, AstraZeneca, Novartis, Pfizer, Bayer, Lilly, Boehringer Ingelheim, Sanofi, Valeant Other: Canadian Cardiovascular Society, Thrombosis Canada Copyright 2013 Canadian Diabetes Association 2

3 Faculty/Presenter Disclosure This program has not received financial support from any commercial organization Potential for conflict(s) of interest: Dr. Bell is on the board of directors of Hypertension Canada Thrombosis Canada Copyright 2013 Canadian Diabetes Association 3

5 Learning Objectives By the end of this session, participants will be able to: 1. Understand the key updates to the Diabetes Canada Guidelines 2. Understand the rationale behind these updates 3. Apply the recommendations in clinical practice Copyright 2013 Canadian Diabetes Association 5

7 Diabetes in Canada: Prevalence of Diagnosed Diabetes by age and sex Prevalence of diagnosed diabetes among individuals aged 1 year, by age group and sex, 2008/09 e (%) Prevalenc Overall Prevalence 30 Females 6.4% Males 7.2% Total 6.8% 5 0 Age group (years) Canada Prevalence increased with age. The sharpest increase occurred after age 40 years. The highest prevalence was in the year age group. Copyright 2013 Canadian Diabetes Association Public Health Agency of Canada. Diabetes in Canada: Facts and figures from a public health perspective. Ottawa,

8 Patients with DM are more likely to be hospitalized for many conditions Public Health Agency of Canada (August 2011); using 2008/09 data from the Canadian Chronic Disease Surveillance System (Public Health Agency of Canada). 8

9 How well are we doing in managing g our patients? 9

Guideline Targets Achieved 60% 57% 50% %

10 Guideline Targets Achieved 60% 57% 50% % of pa atients 40% 20% 36% 13% 0% A1c ( 7%) (n=5103) LDL ( 2.0 mmol/l) (n=5069) SBP/DBP (<130/80 mm HG) (n=5099) All 3 Endpoints (A1c, LDL, BP) (n=5104) Leiter LA et al. Can J Diabetes 2013; in press 10

11 Care gap still exists for screening Within 2 years Canadian Institute of Health Information Diabetes Care Gap

12 What is new in making the diagnosis of diabetes? 12

13 Diagnosis of Diabetes 2013 FPG 7.0 mmol/l Fasting = no caloric intake for at least 8 hours or A1C 6.5% (in adults) Using a standardized, validated assay, in the absence of factors that affect the accuracy of the A1C and not for suspected type 1 diabetes or 2hPG in a 75-g OGTT mmol/l or Random PG 11.1 mmol/l Random= any time of the day, without t regard to the interval since the last meal 2hPG = 2-hour plasma glucose; FPG = fasting plasma glucose; OGTT = oral glucose tolerance test; PG = plasma glucose 13

14 Diagnosis of Prediabetes* 2013 Test Result Prediabetes Category Fasting Plasma Impaired fasting glucose Glucose (IFG) (mmol/l) 2-hr Plasma Glucose in Impaired glucose tolerance a 75-g Oral Glucose (IGT) Tolerance Test (mmol/l) Glycated Hemoglobin (A1C) (%) Prediabetes * Prediabetes = IFG, IGT or A1C % high risk of developing T2DM 14

15 A1C Level and Future Risk of Diabetes: Systematic Review A1C Category (%) 5-year incidence of diabetes <5 to 9% to 25% to 50% Zhang X et al. Diabetes Care. 2010;33:

17 Assessing Risk: Risk Factors for T2DM Personal factors: First-degree relative with T2DM Member of high-risk population (e.g. Aboriginal, African, Asian, Hispanic i or South Asian) History of prediabetes History of gestational diabetes (GDM) History of delivery of macrosomic infant 17

18 Assessing Risk: Risk Factors for T2DM Presence of associated problems: End organ damage complications associated with diabetes Microvascular (retinopathy, neuropathy, nephropathy) Macrovascular (coronary, cerebrovascular, peripheral arterial) Vascular risk factors Low HDL-cholesterol (< 1.0 mmol/l males, 1.3 mmol/l females) Triglycerides 1.7 mmol/l Hypertension, overweight, abdominal obesity 18

19 Assessing Risk: Risk Factors for T2DM Presence of associated problems (continued): Associated diseases Polycystic ovarian syndrome, acanthosis nigricans, obstructive sleep apnea, psychiatric disorders (bipolar, depression, schizophrenia), HIV infection Presence of secondary causes: Use of drugs associated with diabetes Glucocorticoids Atypical antipsychotics Highly active antiretroviral therapy (HAART) 19

20 Can we reduce the risk of developing Type 2 Diabetes? 20

21 Diabetes Prevention Program (DPP) Benefit of diet and exercise or Metformin on diabetes prevention in at-risk patients N = 3234 with IFG and IGT, without diabetes 40 Placebo Cumulative incidence of diabetes (%) Metformin 31% 20 Lifestyle 58% P* < < Years *vs placebo IFG = impaired fasting glucose, IGT = impaired glucose tolerance Diabetes Prevention Program (DPP) Research Group. N Engl J Med 2002;346:

23 2013 Targets Checklist A1C 7.0% 70%for MOST people with diabetes A1C 6.5% for SOME people with T2DM A1C % in people with specific features 23

24 Macro and Microvascular Benefits? diabetes.ca BANTING ( ) 24

25 UKPDS: N = 3867 T2DM A1C (%) Diet only Conventional 79% 7.9% Intensive 7.0% 6 0 UKPDS Study Group. Lancet 1998:352: FPG less than 6 mmol/l using SU and or insulin

26 Legacy Effect of Earlier Glucose Control After median 8.5 years post-trial follow-up Aggregate Endpoint Any diabetes related endpoint RRR: 12% 9% P: Microvascular disease RRR: 25% 24% P: Myocardial infarction RRR: 16% 15% P: All-cause mortality RRR: 6% 13% P: Holman R, et al. N Engl J Med 2008;

27 diabetes.ca BANTING ( ) 27

28 ADVANCE: Glucose Control 10.0 Mean A1C (%) Standard control 7.3% p < Intensive control 65% 6.5% Follow-up (months) ADVANCE Collaborative Group. N Engl J Med 2008;358:24. 28

29 ADVANCE: Treatment Effect on the Primary Microvascular Outcomes New/worsening nephropathy, retinopathy 25 Cumulative incidence (%) HR 0.86 ( ) p = 0.01 Standard control 5 0 Intensive control Follow-up (months) Intensive Standard HR p Nephropathy/retinopathy (%) Nephropathy (%) Retinopathy (%) NS ADVANCE Copyright Collaborative 2016 Canadian Group. Diabetes N Engl Association J Med 2008;358:24. 29

30 diabetes.ca BANTING ( ) 30

31 Consider A1C % if Limited life expectancy High level of functional dependency 2013 Extensive coronary artery disease at high risk of ischemic events Multiple co-morbidities History of recurrent severe hypoglycemia Hypoglycemia unawareness Longstanding diabetes for whom is it difficult to achieve an A1C 7%, despite effective doses of multiple antihyperglycemic agents, including intensified basal-bolus insulin therapy 31

32 Individualizing A1C Targets 2013 Consider % if: which must be balanced against the risk of hypoglycemia 32

33 Exercise: What should we tell patients to do? 33

34 Physical Activity Checklist 2013 DO a minimum of 150 minutes of moderate-to vigorous-intensity aerobic exercise per week INCLUDE resistance exercise 2 times a week SET physical activity goals and INVOLVE a multidisciplinary team ASSESS patient s health before prescribing an exercise regimen 34

35 Who Should be Screened with ECG? Age >40 years Duration of DM >15years + Age >30 years End organ damage Microvascular Macrovascular Baseline resting ECG Repeat every 2 years Cardiac risk factors 35

36 Who Should have Stress Testing and/or Functional Imaging to Screen for CAD? Typical or atypical cardiac symptoms Associated diseases: PAD Carotid bruits TIA Stroke Resting ECG abnormalities (e.g. Q waves) Exercise ECG stress testing If cannot exercise or resting ECG abnormality present: Pharmacologic stress echo Pharmacologic stress nuclear imaging 36

37 Nutrition: What should we tell patients to do? 37

38 Macronutrient Distribution (% Total Energy) Carbohydrates Protein Fat % of total energy 45-60% 15-20% (or 1-1.5g / kg BW) 20-35% Calories per gram Grams for 2000 calorie/day diet BW = body weight 38

39 Choosing Foods Using % Daily Value Daily Values > 15% = a lot Daily Value < 5% = a little 39

40 Choose low glycemic index carbohydrates 40

41 1. Modest weight loss CAN make a difference Goal is to prevent weight gain, promote weight loss and prevent weight re-gain Weight loss of only 5-10% improves: Insulin sensitivity Glycemic control Blood pressure Lipid levels 41

42 Medications for glycemia How do we choose? 42

43 Pharmacotherapy in T2DM checklist 2013 CHOOSE initial therapy based on glycemia gy 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 43

44 AT DIAGNOSIS OF TYPE 2 DIABETES L I F E S T Y L E Start lifestyle intervention (nutrition therapy and physical activity) +/- Metformin A1C <8.5% If not at glycemic target (2-3mos) A1C 8.5% Start metformin immediately Consider initial combination with another antihyperglycemic agent Start / Increase metformin S If not at glycemic gy targets Symptomatic hyperglycemia with metabolic decompensation Initiate insulin +/- metformin Add another agent best suited to the individual by prioritizing patient characteristics: PATIENT CHARACTERISTIC PRIORITY: Clinical Cardiovascular Disease Degree of hyperglycemia Risk of hypoglycemia Overweight or obesity Cardiovascular disease or multiple risk factors Comorbidities (renal, CHF, hepatic) Preferences & access to treatment CHOICE OF AGENT Antihyperglycemic agent with demonstrated t d CV outcome benefit (empagliflozin, liraglutide) Consider relative A1C lowering Rare hypoglycemia Weight loss or weight neutral Effect on cardiovascular outcome See therapeutic considerations, consider egfr See cost column; consider access See next page 11/

45 Class Add another class of agent best suited to the individual (agents listed in alphabetical order): Relative A1C Lowering Hypoglycemi a Weight Effect in Cardiovascular Outcome Trial Other therapeutic considerations glucosidase Rare Neutral to Improved postprandial control, GI side effects effects $$ inhibitor (acarbose) DPP 4 Inhibitors Rare Neutral to alo, saxa, sita: Neutral Cost Caution with saxagliptin in heart failure $$$ GLP 1R agonists to Rare lira: Superiority GI side effects $$$$ with clinical CVD or risk factors lixi: Neutral Insulin Yes Neutral (glar) No dose ceiling, flexible regimens $ $$$$ Insulin secretagogue: Meglitinide Sulfonylurea Yes Yes SGLT2 inhibitors to Rare empa: Superiority in T2DM patients with clinical CVD Less hypoglycemia in context of missed meals but usually requires TID to QID dosing Gliclazide and glimepiride associated with less hypoglycemia than glyburide Genital infections, UTI, hypotension, doserelated changes in LDL C, caution with renal dysfunction and loop diuretics, dapagliflozin not to be used if bladder cancer, rare diabetic ketoacidosis (may occur with no hyperglycemia) $$ $ $$$ Thiazolidinediones Rare Neutral CHF, edema, fractures, rare bladder cancer (pioglitazone), cardiovascular controversy (rosiglitazone), 6 12 weeks required for maximal effect Weight loss agent (orlistat) None GI side effects $$$ $$ Copyright alo=alogliptin; 2016 Canadian glar=glargine; Diabetes saxa=saxagliptin; Association sita=sitagliptin; lira=liraglutide; lixi=lixisenatide; empa=empagliflozin

46 Insulin Secretagogues Antihyperglycemic agents and Renal Function CKD Stage: egfr (ml/min/1.73 m 2 ): < Alpha-glucosidase Inhibitor GLP-1R agonists Biguanide DPP-4 inhibitors Acarbose Not recommended 25 Metformin Alogliptin Not recommended 6.25 mg mg 50 Linagliptin i 15 Saxagliptin mg 50 Sitagliptin 25 mg mg 50 Albiglutide 50 Dulaglutide 50 Exenatide (BID/QW) Liraglutide Gliclazide/Glimepiride Glyburide Repaglinide Canagliflozin mg 60* Dapagliflozin 60 Empagliflozin 45 60* Thiazolidinediones 30 Contraindicated Not recommended Caution and/or reduce dose SGLT2 inhibitors * = guidelines.diabetes.ca do not initiate if egfr < BANTING ml/min ( ) diabetes.ca Safe No dose adjustment but close monitoring of renal function Adapted from: Product Monographs as of March 2016 Harper W et al. Can J Diabetes 2015;39: /

47 47

48 What about Hypoglycemia? 48

49 Definition of Hypoglycemia 1. Development of neurogenic or neuroglycopenic symptoms Neurogenic (autonomic) Trembling Palpitations Sweating Anxiety Hunger Nausea Neuroglycopenic Difficulty Concentrating Confusion Weakness Drowsiness Vision Changes Difficulty Speaking Dizziness 2. Low blood glucose (<4 mmol/l if on insulin or secretagogue) 3. Response to carbohydrate load 49

50 Steps to Address Hypoglycemia y 1. Recognize autonomic or neuroglycopenic symptoms 2. Confirm if possible (blood glucose <4.0 mmol/l) 3. Treat with fast sugar (simple carbohydrate) (15 g) to relieve symptoms 4. Retest in 15 minutes to ensure the BG >4.0 mmol/l and retreat (see above) if needed 5. Eat usual snack or meal due at that time of day or a snack with 15 g carbohydrate plus protein 50

51 Examples of 15 g Simple Carbohydrate 15 g of glucose in the form of glucose tablets 15 ml (3 teaspoons) or 3 packets of sugar dissolved in water 175 ml (3/4 cup) of juice or regular soft drink 6 Lifesavers (1=2.5 g of carbohydrate) 15 ml (1 tablespoon) of honey 51

52 Recognize Risk Factors for Severe Hypoglycemia Risk factors in Type 2 DM patients Elderly Poor health literacy, Food insecurity Increased A1C Duration of insulin therapy Severe cognitive impairment Renal impairment Neuropathy 52

53 Autono mic sympto oms enic s Neuroglycop symptom Older patients have less perception of hypoglycemia *P<0.05 **P<0.01 ** Older ( 65 years) Middle-aged (39-64 years) Baseline Hypo Recovery Baseline Hypo Recovery Bremer JP et al. Diabetes Care. 2009; 32 (8): * 53

54 Macrovascular Disease Vascular Protection: Who and When? 54

55 Who Should Receive Statins? (regardless of baseline LDL-C) yrs old or Macrovascular disease or Microvascular disease or DM >15 yrs duration and age >30 years or Warrants therapy based on the 2012 Canadian Cardiovascular Society lipid guidelines Among women with childbearing potential, statins should only be used in the presence of proper preconception counseling & reliable contraception. Stop statins prior to conception. 55

56 CARDS: Statins Reduced primary CV events in Patients with DM Colhoun Copyright HM, 2016 et al. Canadian Lancet 2004;364:685. Diabetes Association 56

57 If on therapy, target LDL mmol/L 57

58 2013 Dyslipidemia Checklist CHECK lipid profile at diagnosis then yearly OR every 3-6 months when on treatment KNOW when to use statin therapy ADD second line agent only when LDL-C is not at target t despite statin ti therapy USE fibrate when TG 10.0 mmol/l 58

59 2013 Who Should Receive ACEi or ARB Therapy? (regardless of baseline blood pressure) 55 years of age or Macrovascular disease or Microvascular disease At doses that have shown vascular protection [perindopril 8 mg daily (EUROPA), ramipril 10 mg daily (HOPE), telmisartan 80 mg daily (ONTARGET)] Among women with childbearing potential, ACEi or ARB should only be used in the presence of proper preconception counseling & reliable contraception. Stop ACEi or ARB either prior to conception or immediately upon detection of pregnancy EUROPA Investigators, Lancet 2003;362(9386): HOPE study investigators. Lancet. 2000;355: ONTARGET study investigators. NEJM. 2008:358:

60 Micro-HOPE (ACEi): CV Benefits 0.2 Primary Outcome (NNT 22) Placebo 0.16 All Mortality (NNT 31) Kaplan-Me eier rates Ramipril 10 mg MI (NNT 37) RR = 0.75 ( ) p = Stroke (NNT 53) RR = 0.76 ( ) p = CV Death (NNT 29) RR = 0.78 ( ) RR = 0.67 ( ) RR = 0.63 ( ) p = 0.01 p = p = guidelines.diabetes.ca HOPE study investigators BANTING ( ) diabetes.ca Copyright Lancet. 2000;355: Canadian Diabetes Association Duration of follow-up (days) 60

61 ONTARGET: ARB Therapy is as Effective as ACEi for CVD Prevention ONTARGET study investigators. NEJM. 2008:358:

62 Hypertension Checklist 2013 ASSESS for hypertension ( 130/80 mmhg) TREAT to target < 130/80 mmhg USE multiple antihypertensive medications if needed to achieve target (often necessary) USE initial combination therapy if systolic blood pressure > 20 mmhg or diastolic blood pressure > 10 mmhg above target 62

63 Summary of Pharmacotherapy for Hypertension in Patients with Diabetes Threshold equal or over 130/80 mmhg and Target below 130/80 mmhg Diabetes With Nephropathy, CVD or CV risk factors Without the above ACE Inhibitor or ARB 1. ACE Inhibitor or ARB or 2. Thiazide diuretic or DHP-CCB Combination of 2 first line drugs may be considered as initial therapy if the blood pressure is >20 mmhg systolic or >10 mmhg diastolic above target > 2-drug combinations Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACEI or ARB Combinations of an ACEI with an ARB are specifically not recommended in the absence of proteinuria More than 3 drugs may be needed to reach target values If Creatinine over 150 µmol/l or creatinine clearance below 30 ml/min ( 0.5 ml/sec), a loop diuretic should be substituted for a thiazide diuretic if control of volume is desired 63

64 ASA for 1⁰ Prevention in Diabetes Meta analysis of 6 studies (n = 10,117) 117) No overall benefit for: Major CV events MI Stroke CV mortality All-cause mortality JPAD = Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes POPADAD = Prevention of Progression of Arterial Disease and Diabetes PPP = Primary Prevention Project ETDRS = Early Treatment Diabetic Retinopathy Study PHS = Physicians Health Study WHS = Women s Health Study No. of events/no. in group 68/ /638 58/514 ASA Control/placebo RR (95% CI) RR (95% CI) Major CV events JPAD POPADAD WHS PPP ETDRS Total JPAD POPADAD WHS PPP ETDRS PHS Total 20/ / /4789 Myocardial infarction Stroke JPAD POPADAD WHS PPP ETDRS Total De Beradis G, et al. BMJ 2009; 339:b / /638 36/514 5/ / / / / /638 15/514 9/519 92/ / / /638 62/513 22/ / / / /638 24/513 10/ / / / / /638 31/513 10/512 78/ / ( ) 0.97 ( ) 0.90 ( ) 090( ( ) 0.90 ( ) 0.90 ( ) 0.87 ( ) 1.10 ( ) 1.48 ( ) 0.49 ( ) 0.82 ( ) 0.40 ( ) 0.86 ( ) 0.89 ( ) 074( ( ) 12) 0.46 ( ) 0.89 ( ) 1.17 ( ) 0.83 ( ) Death from CV causes JPAD 1/ / ( ) POPADAD 43/638 35/ ( ) PPP 10/519 8/ ( ) ETDRS 244/ / ( ) Total 298/ / ( ) All-cause mortality JPAD POPADAD 34/ /638 PPP 25/519 ETDRS 340/1856 Total 493/ / /638 20/ / / Favors ASA 0.90 ( ) 093( ( ) 21) 1.23 ( ) 0.91 ( ) 0.93 ( ) 2 8 Favors control/placebo 64

65 Recommendation 2013 ASA should not be routinely used for the primary prevention of cardiovascular disease in people with diabetes [Grade B, Level 2] ASA may be used in the presence of additional cardiovascular risk factors [Grade D, Consensus] 65

66 What are the benefits if we do all of the vascular protective steps? 66

67 STENO-2: Intensive Group Achieved Targets Gaede et al. NEJM. 2003: 348;

68 Intensive Group had Improved CV Outcomes P = Any CV event NNT = Conventional therapy Intensive therapy 53 % RRR RRR= relative risk reduction Gaede et al. NEJM. 2003: 348; Months of Follow-up 68

69 STENO 2 Microvascular Disease Gaede et al. NEJM. 2003: 348;

70 Vascular Protection Checklist 2013 A A1C optimal glycemic control (usually 7%) B BP optimal blood pressure control (<130/80) C Cholesterol LDL 2.0 mmol/l if decided to treat D Drugs to protect the heart (regardless of baseline BP or LDL) A ACEi or ARB S Statin A ASA if indicated E Exercise / Eating healthily regular physical activity, achieve and maintain healthy body weight S Smoking cessation 70

71 QUESTIONS? 84 Date of preparation: December

Quick Reference Guide

2013 Clinical Practice Guidelines Quick Reference Guide (Updated November 2016) 416569-16 guidelines.diabetes.ca diabetes.ca 1-800-BANTING (226-8464) Copyright 2016 Canadian Diabetes Association SCREENING