practicing evidence-based diabetes care -...

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Practicing Evidence-based Diabetes Care

Stewart B. Harris, MD MPH FCFP FACPMSonja Reichert, MD MSc FCFP FACPM

Session # 3

Everything you need to know about the 2013 CDA guidelines in order to provide evidence-based diabetes care … … but were afraidto ask!

2013 CDA Clinical Practice Guidelines. Can J Diabetes. 2013;37(suppl 1):S1-S212.


Other resources: http://www.health.gov.on.ca/en/ms/diabetes/en/

It’s all about knowing your ABCDEs!

– A is for A1C

– B is for blood pressure

– C is for cholesterol

– D is for drugs - heart-protecting medications for the right patients

– E is for exercise and other lifestyle measures

– S is for Stop Smoking!


Therapeutic goals

The goal of treatment is to minimizethe risks of macrovascular andmicrovascular complications.

A1C (for most people) ≤7.0%

BP <130/80 mm Hg

LDL-C ≤2.0 mmol/L



Diabetes surveillance schedule

Clinical parameter Screening test(s) and intervals

BG A1C should be measured every 3–6 months, depending on control.

BP At every diabetes-related visit and at least once a year.

Cholesterol Full fasting lipid profile (TC, HDL-C, TG and calculated LDL-C) every year (more frequently if treatment for dyslipidemia is initiated).



CV events Resting ECG at age 40, with repeat testing and/or exercise stress testing every 2 years in people at high risk.

Chronic kidney disease

Annual random urine ACR and a serum creatinine converted to an eGFR. Those with CKD should have an ACR and serum creatinine at least every 6 months.

Neuropathy Annual 10-g monofilament testing.

Foot problems Annual foot examination (more frequently in those at high risk).




Retinopathy Expert funduscopic examination through dilated pupil or digital fundus photography every 1–2 years, depending on whether retinopathy is present. More frequently if retinopathy present.

Erectile dysfunction Periodic sexual function history.

Depression/anxiety

Periodic screening with standardized questionnaire or direct queries.




Blood Glucose Control

Optimizing glycemic controlis fundamental to the management

of diabetes.

Rate your comfort level with CPG-directed hyperglycemia management

a) Not comfortable

b) Comfortable

c) Very comfortable

-ce

ll f

un

ctio

n (

%)

Postprandialhyperglycemia

IGT Type 2diabetesPhase I Type 2

diabetesPhase II

Type 2 diabetesPhase III

25

100

75

0

50

-12 -10 -6 -2 0 2 6 10 14

Years from diagnosis

Patients treated with insulin,metformin, sulfonylureas

Lebovitz HE. Diabetes Rev. 1999;7:139-153.

UKPDS: Beta cell loss over time


Glycemic control over duration of disease

• Control erodes the longer patients have type 2 diabetes.• Only 38% of patients who have had diabetes for 15+ years

are well controlled.

Pat

ien

ts a

t ta

rget

(%

)(A

1C <

7.0%

)

100

80

60

40

20

015+ years(n = 310)

1014 years(n = 364)

69 years(n = 455)

≤2 years(n = 449)

35 years(n = 591)

38%33%

47%

69%

58%

Harris SB. Diabetes Res Clin Pract. 2005:70:90-97.

A1C targetsA1C target ConsiderationsPatients


• Most patients ≤7.0% • Reduces risk of microvascular disease• If implemented early in the course of diabetes,

reduces risk of macrovascular disease

• To further lower risk of nephropathy and retinopathy

≤6.5% • Most appropriate in patients with:- Shorter duration of diabetes- No evidence of significant CVD- Longer life expectancy• Must be balanced against risk of hypoglycemia

• Frail elderly• Limited life expectancy• Advanced comorbidities• History of severe

hypoglycemia• Long-standing diabetes with

failure to attain targets despite treatment intensification

7.1–8.5% • Individualize targets based on circumstances

Fasting and postprandial targets

FPG or preprandial PG

2-hour postprandial PG

Most adults 4.0–7.0 mmol/L 5.0–10.0 mmol/L

If A1C target not achieved

4.0–7.0 mmol/L 5.0–8.0 mmol/L

Both fasting and postprandial plasma glucose levels correlate with the risk of complications and contribute to the

measured A1C value.



UKPDS: Better glucose controlmeans fewer complications

EVERY 1% reduction in A1C REDUCED RISK*

–21%Deaths from diabetes

–14%**Myocardial infarctions

–37%

–43%

Microvascular complications

Peripheral vascular disorders

Adapted from: Stratton IM. BMJ. 2000;321:405-412.

*P <0.0001** ns

UKPDS: legacy effect of earlier glucose control

After median 8.5 years post-trial follow-up (Intensive SU/Ins vs Conventional)

Holman RR, et al. N Engl J Med. 2008;359:1577.

Aggregate Endpoint 1997 2007

Any diabetes-related endpointRRR 12% 9%

P 0.029 0.040

Microvascular diseaseRRR 25% 24%

P 0.0099 0.001

Myocardial infarctionRRR 16% 15%

P 0.052 0.014

All-cause mortalityRRR 6% 13%

P 0.44 0.007

Benefits of an intensive strategy to control blood glucose levels in patients with type 2 diabetes were sustained for up to 10 years after the cessation of randomized interventions. Benefits persisted despite the early loss of within-trial differences in glycated hemoglobin levels between the intensive-therapy group and the conventional-therapy group — a so-called legacy effect.

Diminishedinsulin

LIVER

3. Insulin resistance

PANCREAS

MUSCLE & FAT

Excess glucagon

ISLET

Diminishedinsulin

α-cell produces excess glucagon β-cell produces

less insulin

(And different agents target different defects)

The pathophysiology of type 2 diabetes includes: 4 main defects

Hyperglycemia

2. Excess glucose output

1. Insulin deficiency

GUT4. Diminished incretin effect


Different agents address different defects

Agents Mechanism of action

Metformin Reduces hepatic glucose productionEnhances glucose uptakeIncreases insulin sensitivity

TZDs Improves insulin sensitivity

Acarbose Slows absorption of glucose

Sulphonylureas Stimulate insulin secretion

Meglitinides Stimulate insulin secretion (briefer and more immediate effect than sulphonylureas)

GLP-1s Stimulate insulin secretion in glucose-dependent fashionSuppress glucagon secretionSlow gastric emptyingIncrease satiety

DPP-4s Stimulate insulin secretionDecrease glucagon secretion

New agents for treatinginsulin deficiency

• DPP-4 inhibitors

• GLP-1 receptor agonists

How DPP-4 inhibitors work Januvia (sitagliptin), Onglyza (saxagliptin), Trajenta (linagliptin)

Foodintake

Stomach

GI tract

Intestine

Increases and prolongs GLP-1effect on alpha cells:

Alpha cells:

Pancreas

Insulin release

Net effect:

blood glucose

Beta cells:

Increases and prolongs GLP-1and GIP effects on beta cells:

DPP-4inhibitor

Glucagon secretion

Drucker DJ, Nauck MA. Lancet. 2006; 368:1796-1705.; Idris I, Donnelly R. Diabetes Obes Metab. 2007;9:153-165.; Barnett A. Int J Clin Pract. 2006;60:1454-1470.

Incretins


How GLP-1 receptor agonists workVictoza (liraglutide) and Byetta (exenatide)

Upon ingestion of food …

• GLP-1 is secreted from the L-cells in the intestine.

This in turn …

• Stimulates glucose-dependent insulin secretion.

• Suppresses glucagon secretion.

• Slows gastric emptying.

• Reduces food intake and increases satiety.

Drucker DJ. Curr Pharm Des 2001;7:1399-1412.Drucker DJ. Mol Endocrinol 2003;17:161-171.

PharmacologicManagement of Blood

Glucose

7

6

9

8

A1C

(%

)

10

OAD monotherapy

Diet andexercise

OAD combination

OAD + basal insulin

OAD monotherapy

uptitration

Duration of diabetes

OAD + multiple daily

insulin injections

Conservative management of glycemia: Treatment to failure

A1C = 7%

Adapted from: Campbell IW. Br J Cardiol 2000; 7:625-31.

A1C = 6.5%

OAD = oral antidiabetic


OAD + basal insulin OAD + multiple daily

insulin injections

OAD monotherapy

OAD combinations OADs

uptitration

7

6

9

8

10

Duration of diabetes

A1C = 7%

A1C = 6.5%

Adapted from: Del Prato S, et al. Int J Clin Pract 2005; 59:1345-55.

A1C

(%

)

Aggressive management of glycemia: Treatment to target

OAD = oral antidiabetic

Pharmacologic management of type 2 diabetes

L

I

F

E

S

T

Y

L

E


At diagnosis of type 2 diabetesStart lifestyle intervention (nutrition therapy and physical activity) +/- Metformin

A1C <8.5%

If not at target(2-3 months)

Start/increase metformin

A1C ≥8.5%

Start metformin immediately. Consider initial

combination with another

antihyperglycemic agent

If not at glycemic target

Symptomatic hyperglycemia with

metabolic decompensation

Initiate insulin +/-metformin



Add an agent best suited to the individual:

Patient Characteristics• Degree of hyperglycemia• Risk of hypoglycemia• Overweight or obese• Comorbidities (renal, cardiac, hepatic)• Preferences and access to treatment• Other

Agent Characteristics• BG lowering efficacy and durability• Risk of inducing hypoglycemia• Effect on weight• Contraindications and side effects• Cost and coverage• Other

L

I

F

E

S

T

Y

L

E

L

I

F

E

S

T

Y

L

E


Add an agent best suited to the individual (agents listed in alphabetical order)

Class Relative A1C lowering

Hypo-glycemia

Weight Other therapeutic considerations

Cost

Alpha-glucosidase inhibitor (acarbose)

Rare Neutral to Improved postprandial control, GI side effects

$$

Incretin agents:DPP-4 inhibitorsGLP-1 receptor agonists

to

RareRare

Neutral to GI side effects

$$$$$$$

Insulin Yes No dose ceiling, flexible regimens

$-$$$$

Insulin secretagogue:Meglitinide

Sulfonylurea

Yes

Yes

Less hypoglycemia in context of missed meals but usually requires TID or QID dosing

Gliclazide and glimepiride associated with less hypoglycemia than glyburide

$$

$

TZD Rare CHF, edema, fractures, rare bladder cancer (pioglitazone), CV controversy (rosiglitazone), 6-12 weeks required for maximal effect

$$

Weight loss agent(orlistat)

None GI side effects $$$


L

I

F

E

S

T

Y

L

E

If not at glycemic target

• Add another agent from a different class• Add/intensify insulin regimen

Make timely adjustments to attain target A1C within 3 to 6 months


Clinical considerations when choosing a second-line agent

• Drug coverage

• Duration of disease

• Comorbid conditions

• Degree of hyperglycemia– expected A1C-lowering effect of agents

• Hypoglycemia risk relative to: – occupation

– activity/eating patterns

• Other side effects (e.g. weight gain)

Medications: Reducingthe self-care burden

• Keep lifestyle in the equation

• Tailor regimens to daily habits (same time, place and situation)

• Use once-daily dosing, when possible

• Use combination products, when possible.

• Consider the cost

• Would a dosette help?

• Use your team! Maximize your pharmacist’s role

Case study: Using A1C and SMBG to guide decision-making

• The case:– Adrian is a 51-year-old computer programmer

– Newly diagnosed with type 2 diabetes

– No oral antihyperglycemic agents

– A1C = 8.9%

– Start metformin 500 mg od for 2 weeks (take with largest meal to reduce GI side effects)

– Uptitrate to 1 g bid


6 weeks later: Adrian’s A1C is 7.9%CPG pharmacotherapy options

Which of the following second-line agentswould be best for Adrian?

a) Glyburide (DiaBeta)

b) Gliclazide (Diamicron MR)

c) DPP-4 (Januvia, Onglyza, Trajenta)

d) GLP-1 (Victoza/Byetta)

CPG pharmacotherapy optionsWhich of the following second-line agents

would be best for Adrian?




d) GLP-1 (Victoza, Byetta)

• CONS:− Higher risk of hypoglycemia

in some patients (e.g. elderly, renal/hepatic failure)

− Triggers “defensive eating”

− bid dosing

− Weight gain

− Poor durability in “treat to fail” studies

• PROS:− Inexpensive

− Full formulary coverage

− 1.0–1.5% A1C lowering



b) Gliclazide(Diamicron MR)



• CONS: − Weight gain

− Risk of hypoglycemia (lower than with glyburide)

• PROS:− 1.0–1.5% A1C lowering

− Sustained release

− Convenient od dosing

− Full formulary coverage









• CONS: − <1.0−1.5% A1C lowering

• PROS:− Weight neutral

− Januvia in combination with metformin (Janumet)

− Convenient od dosing

− Single dosing (i.e. no titration)

− Low risk of hypoglycemia








• CONS: − Injectible

− No formulary coverage (expensive)

− Early nausea

• PROS:− Weight loss

− Decreased appetite and earlier satiety

− No hypos

− Easy titration schedule



Can J Diabetes. 2008;32(suppl 1):S1-S201.

Adrian: 4 years later

• A1C = 8.5%

• On max OHAs

• Time to consider insulin therapy:– add bedtime basal insulin

INSULIN STARTS: YOU CAN DO THIS!

Stay tuned to Boot Camp Day 2 …


Natural Health Products

• Used by up to ~80% of diabetes patients

• Not recommended, due to lack of evidence regarding safety and efficacy.

• Potential side effects and drug interactions, and impurities of substances (e.g. heavy metals).

• Expensive and have not undergone the rigorous testing required for pharmaceuticals.

• Commonly used products:– ginseng (BP issues);

– licorice, yerba mate, yohimbine, ginko, psyllium, cinnamon, stevia, St John’s Wort (statin issues); and

– coenzyme Q10, vitamin E, glucosamine.2013 CDA Clinical Practice Guidelines. Can J Diabetes. 2013;37(suppl 1):S1-S212.2008 CDA Clinical Practice Guidelines. Can J Diabetes. 2008;32(suppl 1):S1-S201.

Blood Pressure Control

Rate your comfort level with CPG-directed hypertension management.

a) Not comfortable

b) Comfortable

c) Very comfortable


BP management

• BP should be measured at every diabetes-related clinic visit.

• People with diabetes and elevated BP should be aggressively treated to achieve target BP of <130/80 mm Hg to reduce the risk of both micro-and macrovascular complications.

• Most people with diabetes will require lifestyle interventions and multiple BP-lowering medications to achieve BP targets.

• First-line therapy is an ACE inhibitor or an ARB.


Lipid Control

Rate your comfort level with CPG-directed dyslipidemia management.

a) Not comfortable

b) Comfortable

c) Very comfortable


Importance of Treating LDL-C to Target: Relationship Between LDL-C and

CAD Risk

• This relationship is consistent with a large body of epidemiologic data available from clinical trials of LDL-C-lowering therapy.

• Lower is better! (As low as 1.0 mmol/L)

3.7

2.9

2.2

1.7

1.3

1.0

1.0 1.8 2.6 3.4 4.1 5.0

Re

lati

ve

ris

k f

or

CA

D

(Lo

g S

ca

le)

LDL-C (mmol/L)

1. 4S. Lancet. 1994;344:1383-1389. 2. Sacks FM, et al. Circulation. 1998;97:1446-1452.3. The LIPID Study Group. N Engl J Med. 1998;339:1349-1357. 4. HPS Collaborative Group. Lancet. 2002;360:7-22. 5. LaRosa JC, et al. N Engl J Med. 2005;352. 6. Grundy SM. Circulation. 2004;110:227-239

LDL-C target

Index Target value*

LDL-C ≤2.0 mmol/L

* Generally achievable with statin monotherapy


Complications


Diabetes = CVD

• People with diabetes have a cardiovascular age 10–15 years in advance of their chronological age

• This significantly increases short-term and lifetime risk for CVD, resulting in a reduced life expectancy of ~12 years.

• Many people with diabetes (especially women) will have no symptoms prior to a fatal or non-fatal MI.

• Diabetes confers a 3-fold risk of an acute coronary syndrome


Screening for CAD

• A baseline resting ECG should be performed in patients with any of the following: – >40 years – Duration of diabetes >15 years and age >30

years– End-organ damage– Cardiac risk factors

• A repeat resting ECG should be performed every 2 years

• Exercise ECG stress testing as initial test in the presence of: typical or atypical cardiac symptoms, resting abnormalities on ECG.


Who needs vascular protection?

Population Interventions (alphabetical order)

All people with diabetes

• Lifestyle modifications Achievement and maintenance of a

healthy body weight Healthy diet Regular physical activity Smoking cessation

• Optimize BP control• Optimize glycemic control

Majority of adult patients

• ACE inhibitor or ARB therapy • Lipid-lowering medication (primarily

statins)• Antiplatelet therapy (as indicated for

secondary prevention)



Use a Multifaceted Vascular Protection Strategy

BP <130/80

A1C ≤7%

Rx:StatinsACEi/ARB

Healthy lifestyle/weight

Smoking cessation

Physicalactivity


Know Your ABCDEs

– A is for A1C

– B is for blood pressure

– C is for cholesterol

– D is for drugs - heart-protecting medications for the right patients

– E is for exercise and other lifestyle measures

– S is for Stop Smoking!


Who should be on a statin?

• Those with any of the following:– Clinical macrovascular disease

– Age ≥40 years

– Age <40 years and any of the following:• Diabetes duration >15 years and age >30 years

• Microvascular complications

• Other risk factors*

• Prescribe up to the maximally tolerated and approved dose.


*See 2012 Update of the Canadian Cardiovascular Society Guidelines for the Diagnosis and Treatment of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Available at: www.ccs.ca


Who should be on an ACE inhibitor or ARB?

• Those with any of the following: – Clinical macrovascular disease

– Age ≥55 years

– Age <55 years and microvascular complications

• Use at doses that have demonstrated vascular protection.


Statin / ACE inhibitor / ARB warning!

• In women with childbearing potential:– Use only if there is reliable contraception

– Discontinue prior to conception

– Discontinue if pregnancy occurs.

Who should be on antiplatelet therapy?

• ASA should not be routinely used for the primary prevention of CVD in people with diabetes

• Patients with diabetes and known vascular disease:– low-dose ASA therapy (81–325 mg) may be

considered in people with established CVD

– clopidogrel (75 mg) may be considered in people unable to tolerate ASA



Case study: Managing CV risk

• Bob E., a 56-year-old factory worker, was diagnosed with type 2 diabetes in 2000.

• Patient history and presentation:– A1C: 7.1%

– BP: 150/92 mm Hg

– LDL-C: 3.1 mmol/L

– Albumin to creatinine ratio: 5.6 mg/mmol

• Meds:– Metformin 1 g bid

– Diamicron MR 120 mg od

Managing the ABCs:What is the priority management plan

for this patient?

a) Start a statin

b) Start an ACE or ARB

c) Do a baseline ECG

d) Start aspirin

e) a, b and c

f) All of the above


for this patient?

a) Start a statin



d) Start aspirin

e) A, b and c

f) All of the above

• Statin therapy (targeting LDL-C ≤2.0 mmol/L) should be used to reduce CV risk in adults aged ≥40 years




for this patient?

• ACE or ARB therapy at doses that have demonstrated vascular protection should be used in all patients aged ≥55 years

• Albuminuria (ACR >2.0 mg/mmol) should be treated with an ACE or ARB (even in the absence of hypertension).

a) Start a statin



d) Start aspirin

e) a, b and c

f) All of the above



for this patient?

• A baseline resting ECG should be performed in:– all individuals age >40 yrs

– all individuals (regardless of age) with cardiac risk factors (Bob has hypertension, albuminuria)

a) Start a statinb) Start an ACE or ARB


d) Start aspirin

e) a, b and c

f) All of the above



for this patient?

• ASA is not recommended for primary prevention of CVD

a) Start a statinb) Start an ACE or ARB


d) Start aspirin

e) a, b and c

f) All of the above




for this patient?

a) Start a statin



d) Start aspirin

e) a, b and c

f) All of the above

• The first priority is a multi-faceted reduction of CV risk, targeting :− healthy body weight− diet− exercise− smoking cessation− optimize BP, BG

• For most adults with diabetes:− ACE inhibitor or ARB− Lipid-lowering medications

(primarily statins)



for this patient?

a) Start a statin



d) Start aspirin

e) a, b and c

f) All of the above

• This patient is not a candidate for aspirin therapy.

• He does not have existing CVD.

• Lack of evidence for aspirin as primary prevention for CVD.


Summary• It takes a team to manage diabetes properly

and get “good grades.”

• Treat to target:– Metformin is first choice.

– Consider combination therapy early.

– Many of your patients require and should be on insulin.

• Vascular protection is the #1 priority.


Recruits to mess hall!Report for duty in

45 minutes!

“The Plate Method”This is what we ask our patients to think about. Enjoy your lunch, and remember: “All foods fit!”

practicing evidence-based diabetes care -...

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