Download Jackie T.

Faculty/Presenter Disclosure
• Faculty:
• Relationships with commercial interests:
– Grants/research Support as investigator:
– Consulting fees:,
– Partipated in clinical trials:,
– Other:
2
Faculty/Presenter Disclosure
• Faculty:
• Relationships with commercial interests:
–
–
–
–
Grants/research support:
Speakers bureau/honoraria:
Consulting fees:
Other:
3
Disclosure of Commercial Support
• This program has received financial support from Merck in the form of an
educational grant.
• This program has received in-kind support from Merck in the form of a
modest meal and logistical support.
• Potential for conflict(s) of interest:
– Dr. xyz have received an honorarium from Merck.
– Merck markets products from classes of medication that will be discussed in
this program: Ezetinibe (Ezetrol), Olmesartan (Olmetec) and Sitagliptin
(Januvia).
4
Mitigating Potential Bias
• The information presented in this CME program is
based on recent information that is explicitly
‘‘evidence-based’’.
• This CME Program and its material is peer reviewed
and all the recommendations involving clinical
medicine are based on evidence that is accepted
within the profession; and all scientific research
referred to, reported, or used in the CME/CPD activity
in support or justification of patient care
recommendations conforms to the generally
accepted standards.
5
Learning Objectives
• As a result of this program participants will be
able to:
– Apply time management strategies to optimize a
7–12-minute office visit
– Develop a plan of action for patients presenting
with multiple cardio-metabolic risk factors
– Assess the long-term targets of cardio-metabolic
risk factors in the diabetic population
6
Case: Jackie T.
•
•
•
•
•
•
•
•
•
61 years old
Diagnosed with type 2 diabetes
6 years ago
Had MI with stent 2 years ago
Obese (BMI = 34 kg/m2)
Current BP: 149/84 mmHg (treated)
A1C: 7.5% (treated)
Lipid values (treated):
– TC: 4.8 mmol/L
– LDL-C: 2.3 mmol/L
– TG: 3.7 mmol/L
– HDL-C: 0.83 mmol/L
– TC:HDL-C: 5.8
GFR: 68 mL/min/1.73 m2
Current medications:
– ASA 81 mg qd
– Atenolol 100 mg qd
– Atorvastatin 40 mg qd
– Metformin 850 mg bid
– Ramipril 10 mg qd
– Escitalopram 10 mg qd
– Omeprazole 20 mg qd
– Zopiclone 7.5 mg qhs
– Acetaminophen-codeine prn
A1C = glycosylated hemoglobin; ASA = acetylsalicylic acid; BMI = body mass index; BP = blood pressure;
GFR = glomerular filtration rate; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density
lipoprotein cholesterol; MI = myocardial infarction; TC = total cholesterol; TG = triglycerides
7
Interactive Question:
Kicking Off the Discussion
• You only have scheduled 10 minutes with
Jackie T., what do you do first?
A.
B.
C.
D.
Address BP
Address dyslipidemia
Address hyperglycemia
Address lifestyle modifications
(diet, exercise, etc.)
E. Ask patient how he feels
8
Jackie T.
You go into the room and find Jackie looking
downcast and despondent.
You open the discussion by congratulating him on
getting his blood work completed.
He replies: “I’m not sure I need more bad news
today doc. Maybe something stronger than those
T-3’s for my back pain? Found out my son got
another impaired driving charge last week so my
heart is hurting as much as my back…”
9
Jackie T. (cont’d)
Jackie asks you what he should do about his
son’s suspected drinking problem and also
reveals that he has been taking 2 zopiclone
7.5 mg to get to sleep because of the stress he
is under.
He also reveals that he has been missing work
due to his ‘bad back’ and, furthermore,
wonders if you could look at this mole that has
been changing…
10
Small Table Discussion
1. What do you do now?
2. What resources exist within your medical
practice that would help Jackie T.?
3. How do you get Jackie to focus on his
important health issues?
11
Steno-2: Effect on BP, Lipids and
Glycemia at End of 8-Year
Intervention Period
80
p <0.001
p = 0.21
p = 0.19
p = 0.001
60
Intensive
therapy
40
Conventional
therapy
20 p = 0.06
0
A1C
<6.5%
Cholesterol Triglycerides Systolic BP
< 4.49 mmol/L <1.69 mmol/L <130 mm Hg
Adapted from: Gaede P et al. N Engl J Med 2003; 348(5):383-93.
Diastolic BP
<80 mm Hg
12
Multifactorial Management of Diabetes in Steno-2:
Study Subjects Achieving Specified Targets at End of
13-Year Follow-Up
Patients (%)
Intensive therapy
100
90
80
70
60
50
40
30
20
10
0
p = 0.35
Conventional therapy
p = 0.31
A1C
<6.5%
p = 0.14
p = 0.005
p = 0.27
Cholesterol
<4.49 mmmol/L
DBP = diastolic blood pressure
Adapted from: Gæde P et al. N Engl J Med 2008; 358(6):580-91.
Triglycerides
<1.69 mmol/L
Systolic BP
<130 mmHg
Diastolic BP
<80 mmHg
13
Steno-2: Long-Term Benefits of Multifactorial
Approach in Reducing CV Events and Mortality
Active trial
80
Post-trial follow-up
Relative risk reduction 53%
70
Cumulative incidence of
any CV event (%)
Relative risk reduction; 59%
Absolute risk reduction 29%
P< 0.001
Absolute risk reduction 20%
60
P=0.008
Conventional therapy
50
40
30
Intensive therapy
20
10
0
0
1
2
3
4
5
6
7
8
9
10
11
12
13
Years
CI = confidence interval; CV = cardiovascular; HR = hazard ratio
Adapted from: Gæde P et al. N Engl J Med 2008; 358(6):580-91.
14
Long-Term Follow-Up of Steno-2 Study:
Benefits of Multi-factorial Risk Reduction
• CV event absolute risk reduction 29%:
NNT of 3
• Total mortality absolute risk reduction of 20%:
NNT of 5
• CV mortality absolute risk reduction of 13%:
NNT of 8
NNT = number needed to treat
Adapted from: Gæde P et al. N Engl J Med 2008; 358(6):580-91.
15
Steno-2 (Year 8): Contributions of Risk Factors
to Modification of CV Risk Reduction
Percent of total calculated
risk reduction in CV events
80
60
40
20
0
Lipids
SBP = systolic blood pressure
Adapted from: Gaede P, Pedersen O. Diabetes 2004; 53(Suppl 3):S39-47.
A1C
SBP
16
Interactive Question
• What other healthcare professionals do you feel
would be most helpful in the management of
Jackie T.?
a) Cardiologist or
endocrinologist
b) Psychologist/
social worker
c) Diabetes educator
d) Nutritionist/dietician
e) Nurse
f) Pharmacist
A.
B.
C.
D.
E.
None of the above
C only
A, C and E
C, D and E
All of the above
17
Multidisciplinary Care of Patient with
Cardio-metabolic Risk Factors
Optometrist
PCP
Nurse
Endocrinologist
Podiatrist
Patient
Other
specialists
Exercise
physiologist
Educator
Dietician
Psychologist/
social worker
PCP = primary care physician
Adapted from: Australian Diabetes Educators Association. Multidisciplinary Diabetes Care.
Available at: http://www.adea.com.au/main/forhealthprofessionals/thediabetesteam/multidisciplinarydiabetescare. Accessed: July 4, 2013.
18
Patient-Identified Barriers
to Diabetes Control
1. 56%: psychological (priorities, motivation,
self-efficacy, competing demands, emotional)
2. 26%: external physical
($, access to services etc.)
3. 25%: psychosocial (lack of family support,
family demands, etc.)
4. 24%: internal physical (other conditions,
Rx side effects)
5. 15%: educational (low diabetes knowledge)
Simmons D et al. Diabetes Care 2007; 30(3):490-5.
19
Small Group Activity
• Each table will be given a theme –
– Lipids
– Hypertension
– Glycemic control
– Lifestyle
• In small group, please discuss you action plan
pertaining to your given theme
20
HYPERTENSION
21
Interactive Question: Hypertension
• What is your BP target
for Jackie T.?
A.
B.
C.
D.
E.
<150/90 mmHg
<145/85 mmHg
<140/90 mmHg
<135/85 mmHg
<130/80 mmHg
Jackie T.
• 61 years old
• Diagnosed with type 2 diabetes 6 years ago
• Had MI with stent 2 years ago
• Obese (BMI = 34 kg/m2)
• Current BP: 149/84 mmHg (treated)
• A1C: 7.5% (treated)
• Lipid values (treated):
– TC: 4.8 mmol/L
– LDL-C: 2.3 mmol/L
– TG: 3.7 mmol/L
– HDL-C: 0.83 mmol/L
– TC:HDL-C: 5.8
• GFR: 68 mL/min/1.73 m2
• Current medications:
– ASA 81 mg qd
– Atorvastatin 40 mg qd
– Metformin 850 mg bid
– Ramipril 10 mg qd
– Escitalopram 10 mg qd
– Omeprazole 20 mg qd
– Zopiclone 7.5 mg qhs
– Acetaminophen-codeine prn
22
Interactive Question: Hypertension
• What would be your
next step in helping
Jackie T. reach
this target?
A. Recommend lifestyle
changes
B. Increase dose of
current medication
C. Add another
antihypertensive
medication
Jackie T.
• 61 years old
• Diagnosed with type 2 diabetes 6 years ago
• Had MI with stent 2 years ago
• Obese (BMI = 34 kg/m2)
• Current BP: 149/84 mmHg (treated)
• A1C: 7.5% (treated)
•Current medications:
– Atenolol 100 mg qd
– Ramipril 10 mg qd
23
Interactive Question: Hypertension
• What medication would
you add/change to
reach the BP target?
A.
B.
C.
D.
ARB
Diuretic
CCB
Other
Jackie T.
• 61 years old
• Diagnosed with type 2 diabetes 6 years ago
• Had MI with stent 2 years ago
• Obese (BMI = 34 kg/m2)
• Current BP: 149/84 mmHg (treated)
• A1C: 7.5% (treated)
• Lipid values (treated):
– TC: 4.8 mmol/L
– LDL-C: 2.3 mmol/L
– TG: 3.7 mmol/L
– HDL-C: 0.83 mmol/L
– TC:HDL-C: 5.8
• GFR: 68 mL/min/1.73 m2
• Current medications:
– ASA 81 mg qd
– Atorvastatin 40 mg qd
– Metformin 850 mg bid
– Ramipril 10 mg qd
– Escitalopram 10 mg qd
– Omeprazole 20 mg qd
– Zopiclone 7.5 mg qhs
– Acetaminophen-codeine prn
ARB = angiotensin II receptor blocker; CCB = calcium channel blocker
24
2013 CHEP: Benefit of BP-Lowering in the
“Average” Hypertensive
(i.e., Middle-Aged Male)
NNT (10-Year) to Prevent a CV Event/Death or a Death from All
Causes by BP-Lowering of 12 mmHg
Stage 1
Stage 2
(140–159/
90–99 mmHg)
(≥160/
≥100 mmHg)
No other risk factors
(beyond age and male gender)
60
23
1 other risk factor
16
9
+ CVD or target organ damage
12
9
CHEP = Canadian Hypertension Education Program; CVD = cardiovascular disease
2013 Canadian Hypertension Education Program Recommendations.
Available at: www.hypertension.ca. Accessed: April 18, 2013;
Ogden LG et al. Hypertension 2000; 35(2):539-43.
Hackam DG, et al. Can J Cardiol. 2013;29(5):528-42
25
CHEP: Treatment of Hypertension in
Association with Diabetes – Summary
Threshold ≥130/80 mmHg and Target <130/80 mmHg
With
nephropathy
ACE inhibitor
or ARB
Diabetes
Without
nephropathy
1. ACE inhibitor
or ARB or
2. Thiazide diuretic
or DHP CCB
A combination of 2 first-line drugs
may be considered as initial therapy
if BP is >20 mmHg systolic or
>10 mmHg diastolic above target.
Combining an ACE inhibitor and a
DHP CCB is recommended.
>2-drug
combinations
Monitor serum potassium and creatinine carefully in patients with CKD prescribed an ACE inhibitor or ARB.
Combinations of an ACE inhibitor with an ARB are specifically not recommended in the absence of proteinuria
More than 3 drugs may be needed to reach target values for diabetic patients.
If creatinine >150 µmol/L or creatinine clearance <30 mL/min (0.5 mL/sec), a loop diuretic should be substituted for
a thiazide diuretic if control of volume is desired.
ACE = angiotensin-converting enzyme; CKD = chronic kidney disease; DHP = dihydropyridine
2013 Canadian Hypertension Education Program Recommendations. Available at: www.hypertension.ca. Accessed: April 18, 2013
Hackam DG, et al. Can J Cardiol. 2013;29(5):528-42.
26
2013 CHEP: Follow-Up of BP Above
Targets
• Patients with BP above target are
recommended to be followed at least
every 2nd month
• Follow-up visits are used to:
– Increase the intensity of lifestyle and drug therapy
– Monitor the response to therapy
– Assess adherence
2013 Canadian Hypertension Education Program Recommendations. Available at: www.hypertension.ca. Accessed: April 18, 2013.
Hackam DG, et al. Can J Cardiol. 2013;29(5):528-42
27
LIFESTYLE
28
Assume…
Jackie has a sedentary lifestyle. His diet is
notoriously poor – he admits to having a sweet
tooth with a weakness for pretzels and beer,
which he consumes in excess the 3 nights per
week he plays snooker. He will smoke cigars
during his weekly poker game ‘with the boys’,
and occasionally through the week.
29
GP Dilemma Dialogue
• “But what about diet and lifestyle? Should it
be addressed right off the bat?”
30
Interaction Question: Lifestyle
• How long do you wait for diet and lifestyle
changes to have an impact before you
initiate pharmacotherapy?
A.
B.
C.
D.
E.
4 weeks
6 weeks
3 months
6 months
1 year
31
Interactive Question
• What is the priority for his
lifestyle interventions?
A.
B.
C.
D.
E.
Smoking cessation
Increase physical activity
Healthy eating
Stress management
Moderation of alcohol
32
Interactive Question
• How would you motivate Jackie to achieve
health-related goals?
A.
B.
C.
D.
E.
Outline the long-term consequences
Outline the short-term consequences
Use the concept of CV age
Employ motivational interviewing technique
Refer to an educator
33
Lifestyle Therapies in Adults
with Hypertension:
Summary of Ideal Targets
Intervention
Reduce foods with
added sodium
Weight loss
Target
<1500 mg /day*
BMI <25 kg/m2
Alcohol restriction
<2 drinks/day
Physical activity
Dietary patterns
30–60 minutes 4–7 days/week
DASH diet
Smoking cessation
Smoke-free environment
Waist circumference
Men <102 cm
Women <88 cm
*As of October 2013, the recommended sodium intake limit is 2000 mg/day
2013 Canadian Hypertension Education Program Recommendations. Available at: www.hypertension.ca. Accessed: November 5, 2013.
34
How long should lifestyle modifications
be given to have effect before
pharmacotherapy is initiated?
• CDA:
– A1C <8.5%: can start pharmacotherapy immediately
or allow 2–3 months to achieve target with
lifestyle intervention
– A1C ≥8.5% or symptomatic hyperglycemic with metabolic
decompensation: start immediately
• CCS and CHEP:
– No waiting period recommended
– Lifestyle modification recommended for all regardless of
BP/CV risk level
CCS = Canadian Cardiovascular Society; CDA = Canadian Diabetes Association
Anderson TJ et al. Can J Cardiol 2013; 29(2):151-67;
2013 Canadian Hypertension Education Program Recommendations. Available at: www.hypertension.ca. Accessed: April 18, 2013;
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes 2013; 37(suppl 1):S1-212.
35
Lifestyle Intervention in Steno-2: Percentage of
Patients Reaching Treatment Goals after 8 Years
Intensive
p = 0.58
p = 0.02
Conventional
p = 0.13
p = 0.09
Fat intake
<30%
Saturated fat
<10%
Adapted from: Gaede P et al. N Engl J Med 2003; 348(5):383-93.
Non-smokers
Exercise
>150 min/week
36
LIPIDS
37
Interactive Question: Dyslipidemia
• What are your lipid targets
for Jackie T.?
a)
b)
c)
d)
e)
f)
LDL-C ≤5.0 mmol/L
LDL-C ≤3.5 mmol/L
LDL-C ≤2.0 mmol/L
50% decrease in LDL-C
Apo B ≤0.8 g/L
Non-HDL-C
≤2.6 mmol/L
A.
B.
C.
D.
E.
a only
b only
c only
c and d
c, d, e and f
Apo = apolipoprotein
Jackie T.
• 61 years old
• Diagnosed with type 2 diabetes 6 years ago
• Had MI with stent 2 years ago
• Obese (BMI = 34 kg/m2)
• Current BP: 149/84 mmHg (treated)
• A1C: 7.5% (treated)
• Lipid values (treated):
– TC: 4.8 mmol/L
– LDL-C: 2.3 mmol/L
– TG: 3.7 mmol/L
– HDL-C: 0.83 mmol/L
– TC:HDL-C: 5.8
• GFR: 68 mL/min/1.73 m2
• Current medications:
– ASA 81 mg qd
– Atenolol 100 mg qd
– Atorvastatin 40 mg qd
– Metformin 850 mg bid
– Ramipril 10 mg qd
– Escitalopram 10 mg qd
– Omeprazole 20 mg qd
– Zopiclone 7.5 mg qhs
– Acetaminophen-codeine prn
38
Interactive Question: Dyslipidemia
• What would be your next
step in helping Jackie T.
reach these targets?
A. Recommend lifestyle
changes
B. Increase dose
of atorvastatin
C. Add another
lipid-lowering medication
D. A and B
E. All of the above
Jackie T.
• 61 years old
• Diagnosed with type 2 diabetes 6 years ago
• Had MI with stent 2 years ago
• Obese (BMI = 34 kg/m2)
• Current BP: 149/84 mmHg (treated)
• A1C: 7.5% (treated)
• Lipid values (treated):
– TC: 4.8 mmol/L
– LDL-C: 2.3 mmol/L
– TG: 3.7 mmol/L
– HDL-C: 0.83 mmol/L
– TC:HDL-C: 5.8
• GFR: 68 mL/min/1.73 m2
• Current medications:
– ASA 81 mg qd
– Atenolol 100 mg qd
Atorvastatin 40 mg qd
–
– Metformin 850 mg bid
– Ramipril 10 mg qd
– Escitalopram 10 mg qd
– Omeprazole 20 mg qd
– Zopiclone 7.5 mg qhs
– Acetaminophen-codeine prn
39
Interactive Question: Dyslipidemia
• What medication would
you add/change to
reach the lipid targets?
A.
B.
C.
D.
E.
Atorvastatin 80 mg/day
Other statin
Ezetimibe
Fibrate
Niacin
Jackie T.
• 61 years old
• Diagnosed with type 2 diabetes 6 years ago
• Had MI with stent 2 years ago
• Obese (BMI = 34 kg/m2)
• Current BP: 149/84 mmHg (treated)
• A1C: 7.5% (treated)
• Lipid values (treated):
– TC: 4.8 mmol/L
– LDL-C: 2.3 mmol/L
– TG: 3.7 mmol/L
– HDL-C: 0.83 mmol/L
– TC:HDL-C: 5.8
• GFR: 68 mL/min/1.73 m2
• Current medications:
– ASA 81 mg qd
– Atenolol 100 mg qd
– Atorvastatin 40 mg qd
– Metformin 850 mg bid
– Ramipril 10 mg qd
– Escitalopram 10 mg qd
– Omeprazole 20 mg qd
– Zopiclone 7.5 mg qhs
– Acetaminophen-codeine prn
40
2013 CDA Guidelines for Managing
Dyslipidemia in Individuals with Diabetes
•
Measurement of lipid profile:
– At time of diagnosis of diabetes
– Yearly if lipid-lowering treatment is
not initiated
– Every 3–6 months after lipid-lowering
treatment is initiated
•
Indications for lipid-lowering therapy:
– Clinical macrovascular disease
– Age >40 years
– Age <40 years and 1 of:
• Diabetes duration >15 years and
age >30 years
• Microvascular complications
• Warrants therapy based on the
presence of other risk factors according
to 2012 CCS guidelines
•
•
•
•
Primary target: LDL-C ≤2.0 mmol/L
Additional lipid markers of CVD risk:
apoB, non-HDL-C, TC:HDL-C
1st line therapy: statin
2nd line therapy:
• Includes:
– Bile acid sequestrants
– Cholesterol absorption inhibitor
– Fibrates
– Nicotinic acid
• Should not be routinely added in
patients achieving goal LDL-C
with statin
• May be used to attain LDL-C goal in
individuals not at LDL-C target
despite statin
• For those with TG >10.0 mmol/L,
fibrate should be used to reduce risk
of pancreatitis
Adapted from: Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes 2013; 37(suppl 1):S1-212.
41
Recent Studies: Extending and Confirming Benefit of
LDL-C Lowering Beyond Current Guidelines
30
Statin
25
Placebo
4S
4S
Event
(%)
20
15
LIPID
LIPID
CARE
CARE
10
HPS
HPS
5
TNT
TNT
0
0
1.8
2.3
2.8
3.4
3.9
LDL-C (mmol/L)
4.4
4.9
4S = Scandinavian Simvastatin Survival Study; CARE = Cholesterol and Recurrent Events Trial; HPS = Heart Protection Study;
LIPID = Long-term Intervention with Pravastatin in Ischemic Disease; TNT = Treating to New Targets
Adapted from: LaRosa JC et al. N Engl J Med 2005; 352(14):1425-35.
5.4
42
CTT: No Threshold of LDL-C for Benefit
Relative risk (CI) per
mmol/L LDL-C reduction
Proportional Effects on Major Vascular Events per mmol/L LDL-C Reduction, by Baseline LDL-C
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
<2.0
≥2, <2.5
≥2.5, <3.0
≥3.0, <3.5
≥3.5
Baseline LDL-C (mmol/L)
CTT = Chloesterol Treatment Trialists
Baigent C et al. Lancet 2010; 376(9753):1670–81.
43
GLYCEMIC CONTROL
44
Interactive Question: Hyperglycemia
• What are your blood
glucose targets for
Jackie T.?
a)
b)
c)
d)
e)
A.
B.
C.
D.
E.
A1C <7.5%
A1C <7.0%
A1C<6.0%
FPG 4-7 mmol/L
PPG <8.5 mmol/L
a only
b only
c only
b and d
c, d and e
FPG = fasting plasma glucose; PPG = postprandial plasma glucose
Jackie T.
• 61 years old
• Diagnosed with type 2 diabetes 6 years ago
• Had MI with stent 2 years ago
• Obese (BMI = 34 kg/m2)
• Current BP: 149/84 mmHg (treated)
• A1C: 7.5% (treated)
• Lipid values (treated):
– TC: 4.8 mmol/L
– LDL-C: 2.3 mmol/L
– TG: 3.7 mmol/L
– HDL-C: 0.83 mmol/L
– TC:HDL-C: 5.8
• GFR: 68 mL/min/1.73 m2
• Current medications:
– ASA 81 mg qd
– Atenolol 100 mg qd
– Atorvastatin 40 mg qd
– Metformin 850 mg bid
– Ramipril 10 mg qd
– Escitalopram 10 mg qd
– Omeprazole 20 mg qd
– Zopiclone 7.5 mg qhs
– Acetaminophen-codeine prn
45
Interactive Question: Hyperglycemia
• What would be your next
step in helping Jackie T.
reach these targets?
A. Recommend lifestyle
changes
B. Increase dose of
metformin
C. Add another oral
antihyperglycemic agent
D. Initiate insulin
Jackie T.
• 61 years old
• Diagnosed with type 2 diabetes 6 years ago
• Had MI with stent 2 years ago
• Obese (BMI = 34 kg/m2)
• Current BP: 149/84 mmHg (treated)
• A1C: 7.5% (treated)
• Lipid values (treated):
– TC: 4.8 mmol/L
– LDL-C: 2.3 mmol/L
– TG: 3.7 mmol/L
– HDL-C: 0.83 mmol/L
– TC:HDL-C: 5.8
• GFR: 68 mL/min/1.73 m2
• Current anti-hyperglycemic medications:
– Metformin
850 mg bid
46
Interactive Question: Hyperglycemia
• When would you make
these changes to
his therapy?
A. This visit
B. Follow-up visit, booked as
soon as possible
C. 1 month from now, if
lifestyle changes have
no effect
D. 3 months from now, if
lifestyle changes have
no effect
E. Other
Jackie T.
• 61 years old
• Diagnosed with type 2 diabetes 6 years ago
• Had MI with stent 2 years ago
• Obese (BMI = 34 kg/m2)
• Current BP: 149/84 mmHg (treated)
• A1C: 7.5% (treated)
• Lipid values (treated):
– TC: 4.8 mmol/L
– LDL-C: 2.3 mmol/L
– TG: 3.7 mmol/L
– HDL-C: 0.83 mmol/L
– TC:HDL-C: 5.8
• GFR: 68 mL/min/1.73 m2
• Current medications:
– ASA 81 mg qd
– Atenolol 100 mg qd
– Atorvastatin 40 mg qd
– Metformin 850 mg bid
– Ramipril 10 mg qd
– Escitalopram 10 mg qd
– Omeprazole 20 mg qd
– Zopiclone 7.5 mg qhs
– Acetaminophen-codeine prn
47
2013 CDA CPG Recommended
Targets for Glycemic Control
Glycemic targets must be individualized.
≤7%
7%
6.0%
A target A1C ≤6.5%
may be considered
in some patients
with type 2 diabetes
to further lower the
risk of nephropathy
and retinopathy.
>7%
Most patients
with type 1
and type 2
diabetes
8.5%
Consider if:
• Limited life expectancy
• High level of functional dependency
• Extensive vascular disease
• Multiple comorbidities
• Recurrent severe hypoglycemia
• Hypoglycemia unawareness
• Long-standing diabetes for whom it is difficult to
achieve A1C ≤7.0% despite effective doses of
multiple antihyperglycemic agents including
intensified basal-bolus insulin therapy
CPG = clinical practice guidelines
Adapted from: Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes 2013; 37(suppl 1):S1-212.
48
2013 CDA CPG Recommendations:
Algorithm for Managing Type 2 Diabetes
Initiate lifestyle intervention (physical activity and nutrition therapy) ± metformin.
A1C <8.5%
A1C ≥8.5%
Symptomatic
hyperglycemia
with metabolic
decompensation
• If not at glycemic target
after 2–3 months,
start/increase metformin
• Start metformin immediately
• Consider initial
combination with another
antihyperglycemic agent
• Initiate insulin ± metformin
If not at glycemic targets,
add an agent best suited to the
Individual based on:
Patient characteristics
• Degree of hyperglycemia
• Risk of hypoglycemia
• Overweight or obesity
• Comorbidities (renal, cardiac, hepatic)
• Preferences and access to treatment
• Other
Agent characteristics
• Blood glucose-lowering efficacy
and durability
• Risk of inducing hypoglycemia
• Effect on weight
• Contraindications and side effects
• Cost and coverage
• Other
If not at
glycemic target:
• Add another
agent from a
different class
• Add/intensify
insulin regimen
Make timely adjustments to attain target A1C within 3–6 months.
Adapted from: Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes 2013; 37(suppl 1):S1-212.
49
2013 CDA CPG Recommended
Add-On Antihyperglycemic Therapy
Add an agent best suited to the individual (alphabetical order)
Class
-glucosidase inhibitor
(acarbose)
Incretin agents:
DPP-4 inhibitors
GLP-1 receptor agonists
Insulin
Insulin secretagogues:
Meglitinides
Sulfonylureas
Relative
A1C
lowering
Hypoglycemia
Weight

Rare
Neutral to 

 to 
Rare
Rare
Neutral to 


Yes

• No dose ceiling, flexible regimens

Yes


Yes

• Less hypoglycemia with missed meals
but usually needs tid to qid dosing
• Gliclazide and glimepiride associated
with less hypoglycemia than glyburide
Other therapeutic considerations
• Improved postprandial control
• GI side effects
• GI side effects
Thiazolidinediones

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
Cost
$$
$$$
$$$$
$-$$$$
$$
$
$$
$$$
CHF = congestive heart failure; DPP-4 = dipeptidyl peptidase inhibitor; GI = gastrointestinal; GLP-1 = glucagon-like peptide 1
Adapted from: Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes 2013; 37(suppl 1):S1-212.
50
Meta-analysis: CV Outcomes with
More vs. Less Intensive Glycemic Control
Trials
ΔA1C
(%)
Favours more
intensive
Favours less
intensive
Hazard ratio
(95% CI)
Major CV event
ACCORD
ADVANCE
UKPDS
VADT
-1.01
-0.72
-0.66
-1.16
0.90 (0.78–1.04)
0.94 (0.84–1.06)
0.80 (0.62–1.04)
0.90 (0.70–1.16)
Overall
-0.88
0.91 (0.84–0.99)
(Q = 1.32, p = 0.72, I2 = 0.0%)
MI
ACCORD
ADVANCE
UKPDS
VADT
-1.01
-0.72
-0.66
-1.16
0.77 (0.64–0.93)
0.92 (0.79–1.07)
0.81 (0.62–1.07)
0.83 (0.61–1.13)
Overall
-0.88
0.85 (0.76–0.94)
(Q = 2.25, p = 0.52,I2 = 0.0%)
All-cause mortality
ACCORD
ADVANCE
UKPDS
VADT
-1.01
-0.72
-0.66
-1.16
1.22 (1.01–1.46)
0.93 (0.83–1.06)
0.96 (0.70–1.33)
1.07 (0.81–1.42)
Overall
-0.88
1.04 (0.90–1.20)
(Q = 5.71, p = 0.13,I2 = 47.5%)
0.5
1.0
2.0
Hazard ratio (95% CI)
ACCORD = Action to Control Cardiovascular Risk in Diabetes; ADVANCE = Action in Diabetes and Vascular Disease: Preterax and Diamicron
MR Controlled Evaluation; UKPDS = United Kingdom Prospective Diabetes Study; VADT = Veterans Affairs Diabetes Trial
Adapted from: Turnbull FM et al. Diabetologia 2009; 52(11):2288-98.
51
UKPDS: Long-Term Follow-Up and
Legacy Effect
Intervention
ends
UKPDS
Active
Median A1C (%)
10
9
UKPDS
Follow-up
Conventional
Biochemical
data no longer
collected
8
Intensive
7
6
0
1977
5
10
15
5
1997
10
2007
Years from randomization
Bailey CJ, Day C. Br J Diabetes Vasc Dis 2008; 8(5):242-7;
Holman RR et al. N Engl J Med 2008; 359(15):1577-89.
52
UKPDS: Legacy Effect of Earlier
Glucose Control
Intensive Sulfonylurea/Insulin Therapy vs. Conventional Therapy
After Median of 8.5 Years of Post-trial Follow-Up
RR
*p <0.05
p = log rank; RR = relative risk
Holman RR et al. N Engl J Med 2008; 359(15):1577-89.
53
Take-Home Messages
54