OBESITY:

1
OBESITY
THE CANADIAN EPIDEMIC

AN UPDATE FOR PHARMACISTS
Arya M. Sharma, M.D./PhD, FRCPCProfessor of
Medicine, Chair for Obesity Research
Management, University of Alberta Director,
Weight Wise Program, Alberta Health
Services Scientific Director, Canadian Obesity
Network - Réseau Canadien Obésité 
Tom Smiley B.Sc.Phm., Pharm.D.
Richard Tytus, M.D. Associate ProfessorMcMaster
University Director, FHT Weight Management
program for therapeutic weight loss
2
I have received consulting, speaking and/or
research support from

3
Learning Objectives
After completion of this workshop pharmacists
will be able to

• discuss health risks associated with overweight
  and abdominal obesity
• discuss opportunities to become more involved in
  evidence-based weight management counseling
• use the Principles of the Canadian Obesity
  Clinical Practice Guidelines to recommend
  evidence-based weight management options for
  patients

4
Obesity in Canada an Epidemic
(BMI ? 30, or 30 lbs overweight for 54 woman)
Adults 1985
lt10 10-14 15-19
?20
No Data
Source Katzmarzyk PT. Can Med Assoc J
20021661039-1040.
5
Obesity in Canada an Epidemic
(BMI ? 30, or 30 lbs overweight for 54 woman)
Adults 2004
No Data lt10 10-14
15-19 ?20
Data from Statistics Canada.
6
Weight Distribution in the Canadian Population
Percentage distribution of body mass index (BMI)
categories, by sex, household population aged 18
or older, Canada excluding territories, 2004
Data source 2004 Canadian Community Health
Survey Nutrition E Coefficient of variation
between 16.6 and 33.3 (interpret with
caution) Significantly different from estimate
for Canada (P lt .05)
Nutrition Findings from the Canadian Community
Health Survey Adult Obesity in Canada Measured
Height and Weight. Ottawa, ON Statistics Canada
2004
7
Overweight Canadian Children and Adolescents
Overweight and obesity rates, by sex, household
population aged 2 to 17, Canada excluding
territories, 1978/79 and 2004
Data source 2004 Canadian Community Health
Survey Nutrition Canada Health Survey 1978/79 E
Coefficient of variation between 16.6 and 33.3
(interpret with caution) Significantly different
from estimate for 1978/797(plt0.05)
Nutrition Findings from the Canadian Community
Health Survey Overweight Canadian Children and
Adolescents.Ottawa, ON Statistics Canada 2005.
8
Medical Complications of Obesity
Pulmonary Disease
Idiopathic Intracranial Hypertension
abnormal function obstructive sleep
apnea hypoventilation syndrome
Stroke
Cataracts
Nonalcoholic Fatty Liver Disease
Accelerated Atherosclerosis
steatosis steatohypatitis cirrhosis
Coronary Heart Disease
Diabetes
Dyslipidemia
Gall Bladder Disease
Hypertension
Severe Pancreatitis
Gynecologic Abnormalities
abnormal menses infertility polycystic ovarian
syndrome
Cancer
breast, uterus, cervix, colon, esophagus,
pancreas, kidney, prostate
Osteoarthritis
Skin
Phlebitis
Gout
venous stasis
9
Methodological Issues
Body Mass Index (BMI)

• Weight (kg) / Height (m2)
• Widely used in clinical setting
• Most common measure in population surveys
• Perceived ease of measure
• Intuitive
• Highly correlated with body fat
• No information of fat distribution or body
  composition
• Misclassification (lean muscle mass in male
  athletes)
• Good predictive value for future health risk

10
Relationship Between BMI and Cardiovascular
Disease Mortality
3.0
Men
Women
2.6
2.2
1.8
Relative Risk of Death
1.4
1.0
Lean
Overweight
Obese
0.6
lt18.5
?40.0
18.520.4
23.524.9
22.023.4
30.031.9
35.039.9
20.521.9
25.026.4
26.527.9
28.029.9
32.034.9
Body Mass Index
Calle et al. N Engl J Med 19993411097.
11
Waist Circumference

• WC is highly correlated to total adiposity and to
  BMI
• Preferred to waist/hip ratio
• Only need measuring tape
• Crucial to standardize measurement
• Strong associations with metabolic abnormalities
  of the insulin resistance syndrome
• However, at a given level of WC
• African-American women have less CVD risk factors
  than women of European Origin
• South-Asian men and women have more CVD risk
  factors than their counterparts of European Origin

12
Waist circumference measurement

• The waist circumference is measured by locating
  the upper hip bone and the top of the right iliac
  crest and placing a measuring tape in a
  horizontal plane around the abdomen at the level
  of the iliac crest.
• Before reading the tape measure, the tape should
  be snug but not compressing the skin and should
  be parallel to the floor.
• The measurement is made at the end of normal
  expiration.

Douketis JD, et al. CMAJ. 2005172995-998.
13
Abdominal Obesity Increases the Risk of
Developing Type 2 Diabetes
24
20
16
Relative risk
12
8
4
0
lt71
7175.9
7681
81.186
86.191
91.196.3
gt96.3
Waist circumference (cm)
Carey VJ. Am J Epidemiol. 145(7)614-9 1997  
14
Waist Circumference Correlates Closely with
Intra-Abdominal Adiposity (IAA)
300
r 0.80
Front
200
IAA (cm2)
100
0
Back
60
80
100
120
Waist circumference (cm)
To assess IAA, the simplest anthropometric index
is the measurement of waist circumference, which
is strongly correlated with direct measurement of
IAA by CT scan or MRI, considered to be the gold
standard
AT adipose tissue
Pare A et al. Obes Res. 9(9)526-34 2001
15
Adipocyte as a Secretory Organ
Leptin
Adipsin
Resistin
Adiponectin
LPL
IL-6
FFA
TNF-a
Eicosanoids
CRP?
NO
Angiotensinogen
TGF-a
PAI-1
16
Abdominal Obesity
The Metabolic Syndrome
17
Abdominal Obesity and Waist Circumference
Thresholds

• New IDF criteria

NCEP 2002 International Diabetes Federation
(2005)
18
Treatment of
Obesity
19
Concept of Weight Reductionand Weight Maintenance
Natural course of weight gain
Weight loss phase
Weight maintenance phase
months
years
Time
20
Obesity Treatment Pyramid
21
General Approach to Therapy

• Intervention should begin early
• Clinicians should involve the family and all
  caregivers in the treatment program
• Treatment programs should institute permanent
  changes, not short-term diets or exercise
  programs aimed at rapid weight loss
• A variety of experienced professionals can
  participate in many aspects of a weight
  management program

22
What are the Barriers to Obesity Treatment?

• Obese patients are aware of the need for
  lifestyle modification to manage weight
• Difficulty translating advice into practice
• Unrealistic expectations and goals
• Lack of skills to manage restraint
• Lack of support and sound advice

23
Caloric Intake
(per Person/Year)
of everything.
Eating
more
24
Lifestyle/Diet

• Caloric reduction will cause weight loss
• Estimated caloric deficit of 3500 kcal 1 lb
  (0.45 kg) of fat
• Reducing intake or increasing expenditure
• Usual target is dietary reduction of 500 kcal/day
  to achieve a deficit of 3500 kcal/week (15
  protein, 30 fat)
• Goal steady sustainable dietary change

25
What is a Healthy Diet?

• Carbohydrate 55
• Protein 15
• Fat 30
• Variety
• Moderation

http//www.hc-sc.gc.ca/hppb
26
Balanced Diet Low in Saturated Fat
Red meat and Butter Use Sparingly
White rice, white bread, potatoes, pasta and
sweets Use Sparingly
Dairy, 1 to 2 Servings
Alcohol in moderationUnless Contraindicated
Multiple Vitamins, For Most
Fish, poultry and eggs0 to 2 servings
Nuts and Legumes 1 to 3 servings
Vegetables, In Abundance
Fruit, 2 to 3 Servings
Whole Grain Foods, At Most Meals
Plant Oils, At Most Meals
Daily exercise and weight control
From Willett WC, Stampfer MJ. Sci Am.
200328864-71.
27
Diets
Diets by Condition or Organization

• Mediterranean
• Negative Calorie
• NutriSystem
• Omega
• Peanut Butter
• Perricone
• Pritikin
• Protein Power
• Raw Food
• Revival Soy
• Richard Simmons
• Rosedale
• Rotation
• Scan
• Scarsdale
• Shape Up
• Slim Fast
• Somersizing
• South Beach

• The Abs
• Anne Collins
• Atkins
• Beverly Hills
• Blood Type
• Body for Life
• Cabbage Soup
• Carbohydrate Addicts
• Caveman
• Chicken Soup
• Curves
• Detox
• Eat to Live
• eDiets Weight Loss
• Fat Flush
• Fit for Life
• Food Combining
• French
• Get With the Program

• Acid Reflux
• Acne
• Arthritis
• Attention Deficit Disorder
• Bipolar
• Cholesterol Lowering
• Glutten Free
• Gout
• High Blood Pressure
• Irritable Bowl Syndrome
• Lactose Intolerance
• Menopause
• Migraine Headache
• Pregnancy
• Premenstrual
• Prostate
• Type 2 Diabetes
• American Cancer Society
• American Heart Association

28
Nutrition Therapy

• No single dietary approach is especially
  effective, and there is considerable variability
  in the response of individuals to dietary
  intervention
• A nutritionally balanced diet designed to reduce
  energy intake should be combined with other
  supportive interventions to promote sustainable
  energy deficits and to ensure the maintenance of
  weight loss
• Dietitians and patients need to work together to
  determine the optimal dietary plan on an
  individual basis to promote sustainable weight
  loss

2006 Canadian Clinical Practice Guidelines on the
Management and Prevention of Obesity in Adults
and Children.
29
Nutrition Therapy (continued)

• We suggest a high-protein or a low-fat diet
  (within acceptable macronutrient distribution
  ranges indicated in the Dietary Reference
  Intakes) as reasonable short-term (612 months)
  treatment options for obese adults as part of a
  weight loss program Grade B, Level 2
• There is insufficient evidence to recommend in
  favour or against dietary fibre supplements as
  part of a weight management program
• Meal replacements may be considered as a
  component of an energy-reduced diet for selected
  adults interested in commencing a dietary
  weight-loss program Grade C, Level 2

2006 Canadian Clinical Practice Guidelines on the
Management and Prevention of Obesity in Adults
and Children.
30
Optimal Dietary Therapy for Weight Loss

• Paucity of RCTs!
• Characteristics of an ideal diet
• Hypocaloric - count calories!
• Low energy density - Mediterranean
• High protein - monounsaturated fat
• ? saturated fat (lt 10) fruits / veggies
• Low glycemic index carbs (high fibre) - whole
  grains
• Nutritionally adequate balanced - get enough
  vitamins
• Satiating - ? hunger
• Highly palatable
• No adverse side-effects

31
Components of Energy Balance
Components of Energy Expenditure

• Basal metabolic rate
• (resting energy expenditure)
• Closely related to lean body mass
• Thermic effect of food
• Peak 1 h after meal
• Protein CHO gt fat
• Physical activity

32
Factors Affecting Basal Metabolic Rate (BMR)

• 1. Age Basal Metabolic Rate (BMR)declines as
  you age
• 2. Height tall people have higher BMR
• 3. Growth children pregnant women
• 4. Body composition more lean tissue
• 5. Fever raises BMR
• 6. Stress and stress hormones raise BMR
• 7. Environmental temperature adjusting to
  heat or cold raises BMR
• 8. Fasting / starvation lowers hormones
• 9. Malnutrition lowers BMR
• 10. Thyroid hormones raise BMR

33
Physical Activity and Exercise Therapy Overview
Physical inactivity is common in Canada
80
70
60
50
Physical Inactivity Prevalence ()
Females
40
Males
30
20
10
0
1214
1519
2034
3544
4564
65
Age (years)
Statistics Canada
34
How Much Exercise is Enough to Promote
Maintenance of a Healthy Body Weight?

• For weight management and control in obesity
• Time (duration of activity) is perhaps most
  important
• More time spent in exercise
• More calories burned
• Exercise is for weight management, not fitness
  per se
• So, how much exercise is enough? 13-20
• 30-60 minutes of moderate to vigorous exercise
• Most (preferably all) days of the week

13. Carnethon MR, et al. JAMA. 20052942891-2988.
14. Roberts CK, Barnard RJ. J Appl Physiol.
2005983-30. 15. Kohl HW. Med Sci Sports
Exerc. 200133S472-S483. 16. Stone JA, et al.
In Canadian Guidelines for Cardiac
Rehabilitation and Cardiovascular Disease
Prevention. 200492-114. 17. Oja P. Med Sci
Sports Exerc. 200133S428-S437.
18. Blair SN, et al. Am J Clin Nutr.
200479913S-920S. 19. Institute of Medicine of
the National Academy of Science. Dietary
Reference Intakes for Energy, Carbohydrates,
Fiber, Fat, Fatty Acids, Cholesterol, Protein,
and Amino Acids (Macronutrients). 2002. 20.
Saris WH, et al. Obese Rev. 2003 4 101-114
35
What are the Benefits of Physical Activity and
Regular Exercise on Obesity?21

• Reduced serum LDL
• Reduced serum triglycerides
• Increased serum HDL
• Improved endothelial function
• Reduced dependence of assisted living in latter
  life
• Enhanced weight control
• Increased cardiovascular fitness
• Increased musculoskeletal fitness

• Reduced age-standardized mortality rates
• Reduced plasma fibrinogen levels
• Reduced plasminogen activator inhibitor type 1
• Reduced platelet aggregation
• Reduced inflammatory cytokines including CRP
• Reduction in systemic blood pressure
• Increased insulin sensitivity
• Reduced glucose intolerance

21. Carnethon MR, et al. JAMA.
20052942891-2988.
36
Pharmacologic Targets

• When to Initiate Pharmacotherapy
• Inhibit Absorption - Orlistat
• Appetite Reduction - Sibutramine
• Satiety Enhancement - Sibutramine
• Increase Metabolic Rate -Sibutramine

37
Pharmacotherapy

• We suggest the addition of a selected
  pharmacologic agent in appropriate overweight/
  obese adults who are not attaining clinically
  important weight loss with dietary and exercise
  therapy in order to assist in reducing
  obesity-related symptoms Grade B, Level 2

Lau DCW et al. CMAJ 2007176(8SUPPL) S1-513
38
Pharmacotherapy

• We suggest the addition of a selected
  pharmacologic agent in overweight or obese adults
  with type 2 diabetes, impaired glucose tolerance
  or risk factors for type 2 diabetes who are not
  attaining or unable to maintain clinically
  important weight loss with dietary and exercise
  therapy in order to improve glycemic control
  and/or reduce the risk for developing type 2
  diabetes Grade B, Level 2

Lau DCW et al. CMAJ 2007176(8SUPPL) S1-513,
Canadian Diabetes Guidelines 2008
39
Mechanisms of Action of Orlistat (continued)
30 of triglycerides pass undigested and are
excreted.

Orlistat prevents the absorption of up to 30 of
dietary fat
40
Orlistat Promotes Clinically Significant Weight
Loss
Placebo (n 340)
Orlistat (n 343)
0
P lt .001
-2
-4
6.1
-6
-8
-10
10.2
-12
-4
0
10
20
30
40
52
Week
Sjöström L, et al. Lancet. 1998352167-172.
41
Mechanisms of Action Sibutramine Blocks
Serotonin and Noradrenaline Reuptake
MAO
Reuptake
Catabolism
RELEASE
Serotonin
S sibutramine noradrenaline
serotonin
MAO
Reuptake
Catabolism
RELEASE
S
Noradrenaline
Adapted from Ryan DH, et al. Obes Res.
19953(Suppl 4)553S-559S.
42
Sibutramine mode of action Patients feel full
with less food
Pharmacology of centrally acting agents known to
produce weight loss

• Enhances satiety so patients feel full sooner
• Does not affect the onset of hunger
• Once-daily dosing
• No vitamin supplement required

• MERIDIA is not a releasing agent and does not
  increase release of serotonin
• Achieves therapeutic effect via serotonin and
  norepinephrine reuptake inhibition (SNRI)

Sharma M, European Heart Journal Supp.(2005)
L39-L43
43
Sibutramine Incidence of Adverse Events (gt5)
in Obese Patients
Statistically significant compared with placebo
(P lt 0.5) Data on file, Abbott Laboratories
44
STORM Mean Body Weight Changes During Weight
Loss and Weight Maintenance Phases over 2 Years
Weight loss
Weight maintenance
104
Control
102
100
98
Body Weight (kg)
96
94
92
90
Sibutramine
88
0
12
2
4
6
8
10
14
16
18
20
22
24
Month
James WPT, et al. Lancet. 20003562119-2125.
45
The STORM Study Effect of Sibutramine on Weight
Maintenance After Weight Loss
Sibutramine vs. Placebo at 24 months (sibutramine
n 206, placebo n 57)
9.2cm
10.2kg
43
4.5cm
4.7kg
16
Placebo
Sibutramine
Sibutramine
Placebo
Placebo
Sibutramine
James WPT, Astrup A, Finer N, et al for the STORM
Study Group, Effect of sibutramine on weight
maintenance after weight loss a randomized
trial. Lancet 2000 356 2119-25
46
CV side effects in sibutramine trials
Adapted from Sharma AM. IJO, 2001
47
SCOUT Sibutramine Cardiovascular Outcomes Trial

• Single blind 6 week lead in period
• 10,742 patients
• 97 CV disease, 88 HTN, 84 T2D
• ? WC by 2.0 cm
• Patients discontinued Tx if
• ? bp gt 10 mm Hg (4.7) or ? HR (3.5) by 10 bpm
  at 2 consecutive visits
• Majority of patients withdrawing due to bp
  criteria originally had bp lt 140/90 mm Hg

Torp-Pedersen C, et al. Eur Heart J
2007282915-2923
48
Lifestyle Modification to be included ALWAYS

• 224 obese adults sibutramine or lifestyle or
  both
• 1200-1500 Calorie diet and same exercise
• At one year
• Combined lost 12.1 kg
• Sibutramine alone lost 5.0 kg
• Lifestyle alone lost 6.7 kg
• Sibutramine plus brief counselling lost 7.5 kg

Wadden T, et al. N Engl J Med 20053532111-2120
49
The class of serotonin and norepinephrine
reuptake inhibitors (SNRIs)

• venlafaxine (Effexor)
• venlafaxine XR (Effexor XR)
• desvenlafaxine succinate (Pristiq)
• milnacipran (Ixel)
• duloxetine (Cymbalta)
• Additional dual serotonin and norepinephrine
  reuptake inhibitors
• Sibutramine (Meridia)
• tramadol (K opiate agonist)

50
SNRIs Class Side-Effects

• Acute adverse events are transitory, with
  resolution or improvement in the first 2-4 weeks
  of treatment.
• TIP Patient education imperative in adherence.
• Sustained adverse events persist beyond 6 months.
• TIP These side effects in most cases resolve
  themselves after stopping taking the SNRI.

Cymbalta package insert. Eli Lilly and Company
May 2007. Effexor XR package insert.
Wyeth-Ayerst March 2007 Meridia package
insert. Abbott Laboratories May 2005Perahia DG,
Pritchett YL, Kajdasz DK, et al. J Psychiatr
Res., 2007. Eckert L, Lancon. BMC Psychiatry.
2006630. Anderson IM.. Br Med Bull.
200157161-178 Stahl SM, Grady MM, Moret C,
Briley M. CNS Spectr. 200510(9)732-47.
Dell'Osso B, et al. J Clin Psychiatry.
200667(4)600-610. Shelton CI. J Clin
Psychiatry. 200465(Suppl 17)29-33. Vis PM, et
al.. Ann Pharmacother. 200539(11)1798-1807.
Williams K, Reynolds MF. CNS Spectr. 200611(8
Suppl 9)19-23. Zajecka JM, J Clin Psychiatry.
200465(Suppl 17)11-18.
51
Cardiovascular Effects
52
Nota Bene

• Hypertension is not a contraindication for use of
  any serotonergic-noradrenergic reuptake
  inhibitors or stimulants
• As a rule, stabilize blood pressure first before
  commencing treatment
• In the event of drug-induced hypertension, risks
  versus benefits should be assessed leading to
  patient-centered decisions

53
OTC Weight Loss Products The Bottom Line

• No credible evidence of efficacy for currently
  available products
• Many potentially unsafe

1

• Natural Medicines Comprehensive Database 2007
• Anderson JW, et al. Ann Pharmacother
  2006401717-1723

54
National Institutes of Health Consensus
Conference March 2527, 1991

• Medical therapies generally fail to control
  severe obesity
• Surgery should be considered for individuals with
  BMI 40 kg/m2
• With comorbidities of obesity, such as diabetes
  or sleep apnea, consider surgery with BMI 35
  kg/m2

55
Bariatric Surgical Procedures
56
Bariatric Surgery Produces Sustained Long-term
Weight Loss
5
0
Control
Weight Change ()
-5
Banding
-10
-15
Vertical banded gastroplasty
-20
-25
Gastric bypass
-30
-35
-40
-45
0.0
0.5
1.0
2.0
3.0
4.0
6.0
8.0
10.0
Years of Follow-up
No. of Subjects
Control Banding Vertical banded
gastroplasty Gastric bypass
563 156 417 32
642 147 412 32
535 144 401 29
627 156 451 34
585 150 438 34

627 156 451 34
594 154 438 34
587 153 438 34
577 149 429 33
Sjostrom L, et al. N Engl J Med.
20043512683-2693.
57
Bariatric Surgery Cures / Improves Type II
Diabetes
100
Type II DM
87.0
80
Controls
60
Gastric Bypass
40
20
8.6
0
(69-year follow-up)
MacDonald KG, et al. J Gastrointest Surg.
19971213-220.
58
Effects of Bariatric Surgery on Medication and
Nutrient Administration

• Solubility of drug, surface area for absorption,
  pH affect oral absorption and bioavailability
• Drugs in aqueous solution more rapidly absorbed
  than those in oily solutions, suspensions or
  solids
• Potential ? absorption for drugs that require
  acid for dissolution
• Large ? surface area for absorption (affects
  drugs with long absorptive phases such as
  enteric-coated)

Miller AD, Smith KM. Am J Health System Pharm
2006631852-1857
59
Recommended Supplements for Patients after
Bariatric Surgery

• All patients should receive daily multivitamin
  and calcium supplementation indefinitely
• Patients with anemia iron ( Vit C), Vit B12,
  folate may be necessary
• See handout for selected agents with potential
  for decreased absorption

60

• Overweight or obese adult
• Measure BMI
• Measure waist circumference if BMI is gt25 and
  35 kg/m2

• Important Message
• A modest weight loss of 5-10 of body weight is
  beneficial.
• Weight maintenance and prevention of weight
  regain should be considered as long-term goals.

If BMI is gt 25 kg/m2 or waist circumference is
above cutoff point
Devise goals and lifestyle modification program
for weight loss and reduction of risk
factors Weight-loss goal 5-10 of body weight,
or 0.5 1kg (1-2l b) per week for 6 months.
Conduct clinical and laboratory investigations to
assess comorbidities (Blood pressure, heart rate,
fasting glucose, lipid profile total
cholesterol, triglycerides, LDL and HDL
cholesterol, and ratio of total cholesterol to
HDL cholesterol)
Health team to advise lifestyle modification
program.
Assess and screen for depression, eating and mood
disorders
Lifestyle modification program Nutrition Reduce
energy intake by 5001000 kcal/dPhysical
activity Initially 30 minutes of moderate
intensity 3-5 times/wk eventually 60 minutes
on most days. Add endurance exercise training.
(Medical evaluation is advised before starting
activity program)Cognitive-behavior therapy
Treat comorbidities and other health risks if
present.
Assess readiness to change behaviors and barriers
to weight loss
Satisfactory progress or goal achieved?
YES
NO
NO

• Regular monitoring
• Assist with weight maintenance
• Reinforce healthy eating and physical activity
  advice.

• Weight maintenance and prevention of weight
  regain
• Nutrition therapy
• Physical activity
• Cognitive-behavior therapy
• Address other risk factors periodic monitoring
  of weight, BMI and waist circumference every 1-2
  years.

• Pharmacotherapy
• BMI 27 kg/m2 risk factors
• or
• BMI 30 kg/m2
• Adjunct to lifestyle modification consider if
  patient has not lost 0.5 kg (1lb) per week by 3-6
  months after lifestyle changes.

• Bariatric surgery
• BMI 35 kg/m2 risk factors
• or
• BMI 40 kg/m2
• Consider if other weight loss attempts have
  failed. Requires lifelong medical monitoring.

61
What Can We Do in Our Pharmacies?

• Weight management programs
• Clinic Days
• Support groups (e.g., walking)
• Signage/Bag stuffers/Literature
• Measuring tapes/Monitoring
• Community speaking programs

62
Case Studies
63
Case Studies