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The Obesity Epidemic: This is your Life

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Title: The Obesity Epidemic: This is your Life


1
The Obesity Epidemic This is your Life
  • Block 10
  • April, 2004
  • Arlo Kahn, M.D.
  • UAMS Dept. of Family and Preventive Medicine
  • Arkansas Center for Health Improvement
  • UAMS College of Public Health

2
Objectives
  • Whats happening?
  • What are patients doing?
  • Diets, drugs, activity
  • What can physicians do?
  • Counsel, prescribe, cut, advocate

3

4
Obesity Trends Among U.S. Adults BRFSS, 1988
(BMI ? 30, or 30 lbs overweight for 54
person)
5
Obesity Trends Among U.S. Adults BRFSS, 1990
6
Obesity Trends Among U.S. Adults BRFSS, 1991
7
Obesity Trends Among U.S. Adults BRFSS, 1992
8
Obesity Trends Among U.S. Adults BRFSS, 1993
9
Obesity Trends Among U.S. Adults BRFSS, 1994
10
Obesity Trends Among U.S. Adults BRFSS, 1995
11
Obesity Trends Among U.S. Adults BRFSS, 1996
12
Obesity Trends Among U.S. Adults BRFSS, 1997
13
Obesity Trends Among U.S. Adults BRFSS, 1998
14
Obesity Trends Among U.S. Adults BRFSS, 1999
Source BRFSS, CDC.
15
Obesity Trends Among U.S. Adults BRFSS, 2000
16
Obesity Trends Among U.S. Adults BRFSS, 2001
Source Mokdad A H, et al. JAMA 20032891
Source Mokdad A H, et al. JAMA
19992821620032891
17
Obesity Trends Among U.S. Adults BRFSS, 2002
Source Mokdad A H, et al. JAMA 20032891
Source Mokdad A H, et al. JAMA
19992821620032891
18
US Adult Obesity Prevalence
  •   NHANES 1999-2000      Predicted
    2010 
  •    
  • Black Women    50.0             
    57.0              White Women   30.8             
      40.0               Black Men       
    28.7               33.0              
  • White Men        27.8              
    37.7   
  •   L Roux, MM Yore, NAASO 2003 Annual Scientific
    Meeting          

19
Actual Causes of Death in the United States, 1990
Source McGinnis JM, Foege WH. JAMA
19932702207-12.
20
Actual Causes of Death in the United States, 2000
  • Tobacco
  • 435,000 deaths
  • Poor diet and physical inactivity
  • 400,000 deaths
  • Poor diet and physical inactivity may soon
    overtake tobacco as the leading cause of death

Mokdad, AH et al. JAMA. 20042911238-1245
21
RAND Research
  • Obesity is linked to rates of chronic illnesses
    higher than living in poverty, and much higher
    than smoking or drinking.
  • Sturm R. The Effects of Obesity, Smoking, and
    Problem Drinking on Chronic Medical Problems and
    Health Care Costs. Health Affairs.
    200221(2)245-253.
  • Sturm R, Wells KB. Does Obesity Contribute As
    Much to Morbidity As Poverty or Smoking? Public
    Health. 2001115229-295

22
The Risks of Overweight
  • coronary heart disease, congestive heart failure
  • cancer of breast, prostate, colon, uterus, liver,
    kidney, pancreas, esophagus
  • stroke
  • Arthritis, gout
  • gallbladder disease
  • incontinence, poor female reproductive health
  • sleep apnea, asthma, other respiratory problems
  • hypertension, diabetes mellitus, high cholesterol

23
The Costs 2000
  • Cost of obesity in U.S.
  • 117 Billion (gt17 increase from 1996)
  • Cost of obesity in Arkansas
  • 1.2 Billion
  • 9.4 percent of the national health care
    expenditures in the United States are directly
    related to obesity and physical inactivity

24
Obesity in Arkansas
  • 7th highest rate of physical inactivity
  • 84.6 of Arkansas adults are at risk for health
    problems related to lack of exercise
  • 21 percent increase in the number of Arkansans
    who have diabetes from 1993 2000
  • Type 2 diabetes at ACH
  • 2 cases in mid 90s
  • gt100 cases last year

25
Adult BMI Chart
Weight (lbs)
260
270
280
290
300
190
200
210
220
230
240
250
120
130
150
160
170
180
140
5'0"
5'2"
5'4"
5'6"
Height
5'8"
5'10"
6'0"
6'2"
6'4"
26
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27
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28
Girls 2 to 20 years
29
Percentage of U.S. Children and Adolescents Who
Were Overweight
Ages 12-19
Ages 6-11
1963-70 data are from 1963-65 for children 6-11
years of age and from 1966-70 for adolescents
12-17 years of age gt95th percentile for BMI by
age and sex based on 2000 CDC BMI-for-age growth
charts Source National Center for Health
Statistics
30
Percentage of U.S. Children and Adolescents Who
Were Overweight
14
13
Ages 12-19
5
4
Ages 6-11
gt95th percentile for BMI by age and sex based
on 2000 CDC BMI-for-age growth charts Data are
from 1963-65 for children 6-11 years of age and
from 1966-70 for adolescents 12-17 years of
age Source National Center for Health
Statistics
31
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32
84th General Assembly Act 1220 of 2003 AN ACT
TO CREATE A CHILD HEALTH ADVISORY COMMITTEE TO
COORDINATE STATEWIDE EFFORTS TO COMBAT CHILDHOOD
OBESITY AND RELATED ILLNESSES TO IMPROVE THE
HEALTH OF THE NEXT GENERATION OF ARKANSANS AND
FOR OTHER PURPOSES.
33
The Arkansas BMI Initiative
  • Act 1220
  • Beginning in the 2003-2004 school year, each
    school district shall annually
  • Measure the BMI of each K-12th grade student and
    report it to parent
  • Explain to parents the possible health effects of
    body mass index, nutrition and physical activity

34
The Numbers
  • In May, 2004 BMI health letters will go out to
    parents of 450,000 Arkansas public school
    students.
  • Based on data from the Cambridge schools, 34 of
    students may be in the overweight or risk of
    overweight categories, with about 17 in each
    category.
  • In the Cambridge study on response to BMI report
    cards (1396 elementary students), parents of 25
    of children in these categories reported that
    they planned to seek medical service for this
    problem.
  • 3. If Arkansas numbers are similar, it is
    possible that parents of 38,000 students will
    seek medical care related to the BMI report.
    (450,000 x .34 x.25 38,250.)

35
Rationale for the BMI Initiative
  • Treatment of adult obesity has had less than
    satisfactory outcomes. Prevention is most
    promising.
  • Overweight school-age children have a 50
    probability of becoming obese adults.
  • Overweight adolescents have a 70-80 probability
    of becoming obese adults.
  • Many children do not make regular doctor visits,
    and when they do, BMI is not routinely checked.
    (2002 study found that less than 20 of
    pediatricians were checking BMI.)
  • While parents often recognize when their children
    are extremely overweight, many parents do not
    recognize less extreme overweight that still
    poses health and emotional risks to their kids.
  • Many parents do not know the risks of overweight.

36
Rationale for using BMI in Children and
Adolescents to Assess for Weight-related Risks
  • 95th percentile for age corresponds to BMI of 30
    in young adult (obesity)
  • 85th percentile for age corresponds to BMI of 25
    in young adult (overweight)
  • Compared with DEXA, 95 of children with BMI
    gt95th percentile had increases in body fat
  • BMI percentile predicts CVD risk
  • 60 of 5-10 year old kidsgt95th percentile
    have at least 1 additional risk, 15 have 2 or
    more

37
BMI in Children and Adolescents Limitations
  • Weight and height do not directly measure body
    fatness
  • Additional criteria are necessary to determine
    whether someone with BMIgt95th percentile is
    overfat (e.g. tricep skinfold thickness) as
    opposed to overweight because of increased muscle
    or bone mass
  • Changes in BMI over time may be as important as
    single reading

38
What are your patients doing about obesity?
  • 29 of men and 44 of women trying to lose weight
  • About 20 of report restricting calories or
    increasing physical activity

39
What Can Physicians Do
  • Counsel
  • Diets
  • Drugs
  • Surgery
  • Advocacy

40
Treating Obesity Without Frustration
41
Goal
  • Learn how to work with obese patients in a manner
    that is effective, minimizes physician
    frustration, shows respect for the patient and
    maintains good communication

42
PROBLEM CAD and Type II DM S Ms. X is a 35
year old who was diagnosed as having diabetes
sometime in the last several months at the time
of her admission for angioplasty with two
coronary stents placed in her LAD. She is
currently taking 10 mg of Glipizide b.i.d. and 12
units of Humulin 100 at night. She says that she
checks her BS up to 4 times q.d., and they are
always in the upper 100s and lower 200s. She
takes Monopril 10 mg. q.d., Lipitor 10 mg. b.i.d.
, aspirin 325 mg. enteric coated, and Prozac 40
mg. q.d. She has lost l5 lbs. since her
diagnosis, approximately 3 months ago, but has
not lost any weight recently. Smokes 1ppd. O
Current weight is 235. Height is 54. BMI
40.5.
43
  • Assuming you want to address her obesity, how
    would you proceed?

44
The Good Old 4-A Technique
  • ASK
  • ADVISE
  • ASSIST
  • ARRANGE

45
ASK
  • Assess readiness to change
  • Do you want to work on losing weight?
  • If ready, assess previous and current efforts and
    obstacles

46
When asked if she is interested in addressing any
of her lifestyle issues at this time she said
that she would be interested in addressing her
weight. She is supposed to be on a l500 calorie
diet, but she has never really counted calories,
so she is not sure what she is actually
consuming. She is not able to identify any
single foods that she eats frequently that she
thinks are bad for her. She drinks 2 milk, and
apparently has several servings a day. She was
unaware that this is actually high fat milk.
She is supposed to be exercising about 30
minutes 3 times a week, but rarely does more than
twice a week. She doesn't like exercise and
doesn't like dieting. She feels that being
asymptomatic with regard to respiratory,
cardiovascular, GI, and musculoskeletal systems
reinforces her lack of motivation.
47
Readiness to Change
  • Precontemplation (not interested)
  • Contemplation (6 months)
  • Preparation (within a month)
  • Action (working on it)
  • Maintenance

48
Obstacles
  • Unaware of current intake
  • Unaware of high calorie foods
  • Doesnt like exercise or dieting
  • Feels fine

49
ADVISE
  • Give brief personalized advice
  • her risks of overweight
  • benefits to her of controlling weight

50
ASSIST
  • How to assist depends on Stage of Readiness to
    Change!!!

51
Assist (Readiness Stage Preparation)
  • Provide educational materials
  • Test Motivation Give diet diary (3-7 day)
  • Decrease obstacles
  • Inform of support programs available in the
    community
  • Counsel or refer as needed for counseling

52
She is not willing to go to Weight Watchers. She
is willing to keep a diet diary for a week and
return then to review it.
53
Arrange
  • Plan
  • 1) Discussed motivation and personal value of
    weight loss. She is willing to do a diet diary
    for a week and return in 1 week with those
    results, at which time we will review the diary.
    In the meantime, she says that she will also be
    willing to increase her walking to 3 times a
    week.
  • 2) I have referred her to Dr. Z for counseling to
    examine possibilities for increasing motivation
    to improve her lifestyle.

54
Treating Obesity Without Frustration
  • Assess readiness to change
  • Assess barriers to change
  • Use appropriate tools to assess motivation
  • Address obstacles creatively
  • Determine whether referral is appropriate and to
    whom patient should be referred
  • Frequent follow-up for patients in preparation,
    action, or maintenance

55
Pearls for Treating Kids
  • Self-monitoring is one of most helpful tools.
    Have them record physical activity and diet on
    daily basis, weight every 2-4 weeks. Review when
    patients come back and give praise where
    appropriate.
  • Work on stimulus control
  • Set limits on screen time (2 hrs/ day). No TV
    while eating.
  • Remove snacks from view. Put out fruits and
    vegetables.
  • No seconds.
  • Regular meal times including breakfast.
  • Fist size portions only.

56
  • Physical activity-anything that raises breathing
    and heart rates (brisk walking, bicycling,
    dancing).Work up to one hour/day.
  • Nutrition- increase fruits and vegetables, skim
    and 1 milk. Decrease sugar drinks and high
    saturated and trans fat foods (fast food and
    candies)
  • Give children attention and provide role models.
    Eat and play together.
  • If above fails, portion control, poor compliance
    or emotional problems may be the answer.
  • Support groups can be helpful if available.
  • Referral is appropriate if co-morbidities are
    found that do not respond to efforts above and
    for discovery of abuse or other severe
    psychopathology.

57
Diets and Drugs for Obesity A Critical Review
58
AHA Guidelines for Healthy Diets
  • Protein 15-20 of calories
  • not excessive (50-100g/d)
  • proportional to carbohydrate and fat
  • Carbohydrates 55 of calories Minimum of 100g/d
  • Fat 30 of calories, lt10 sat fat
  • Protein foods should not contribute excess total
    fat, sat fat or cholesterol
  • Diet should provide adequate nutrients and
    support dietary compliance

St. Jeor ST, etal. Circulation 1041869-74, 2001.
59
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60
Categorization of Diets by CHO and Fat
Riley RE. Clinics in Sports Medicine.
18(3)691-701, 1999.
61
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62
Atkins Diet Revolution
Rap
Riley RE. Clinics in Sports Medicine.
18(3)691-701, 1999.
63
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64
The Zone
Rap
St. Jeor ST, etal. Circulation 1041869-74,
2001. Riley RE. Clinics in Sports Mediicne.
18(3)691-701, 1999.
65
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66
Protein Power
Rap
Riley RE. Clinics in Sports Mediicne.
18(3)691-701, 1999.
67
High Protein Effects
  • Diuresis (limited to 1st week)
  • Mobilization of glycogen stores cause weight
    loss of 1 kg
  • Generation of ketones
  • Reductions in caloric content
  • Appetite suppression from ketosis
  • No studies have demonstrated advantages of
    ketotic diet

Denke M. Am J Cardiology 88(1)59-61,
2001. St.Jeor ST, et al. Circulation
1041869-1874, 2001.
68
High protein Metabolic Effects
  • Ketosis
  • dehydration, constipation and kidney stones
  • fatigue
  • ??? alter cognitive functioning
  • High Saturated Fat
  • Increases in LDL-C and TC
  • Low Fruits, Vegetables and Grains
  • Deficient in micronutrients (Vitamin B, calcium,
    K) and phytochemicals
  • Increases in serum uric acid

Denke M. Am J Cardiology 88(1)59-61, 2001.
St.Jeor ST, et al. Circulation 1041869-1874,
2001. Westman EC. Et al. Am J Med. 113(1) 30-6,
2002.
69
Other possible effects
  • Kidney stones
  • Osteoporosis
  • Chronic renal insufficiency

70
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71
Sugar Busters
Rap
72
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73
South Beach Diet
  • Phase 1 two weeks. Most should see a rapid
    weight loss of between 8 13 pounds. Most
    restrictive.
  • Phase 2 until reach goal weight. Weight loss
    1-2 pounds per week. Foods that were restricted
    in re-introduced into the diet.
  • Phase 3 for life. Restrictions avoid highly
    processed food that contains bad carbs and
    bad fats and try and stick to the food that
    contains the good ones.

74
Structure
  • Studies suggest that adding structure to dietary
    recommendations improves weight loss in the
    behavioral treatment of obesity.
  • Structure reduces the effort required for
    adherence, and eliminates much of the decision
    making, temptation, and guesswork involved in
    making healthy food choices.

75
Weight Watchers
  • Practical advice
  • Group techniques
  • Food variety
  • Moderate protein, low fat
  • Limits refined sugars and EtOH
  • Stresses activity
  • Groups
  • Very structured
  • Weekly fees

76
Structured Meal Plans
  • Providing patients with structured meal plans and
    grocery lists produced just as great a weight
    loss at 6 months (13.7) as did providing them
    with portion-controlled servings of food (13.5).
  • The findings of this study indicate that
    specifying what foods and what amounts patients
    should eat improves weight loss, but that
    providing the food has no additional effect.

77
Protein Sparing Modified Fast (Optifast,
Medifast)
  • Calorie intake usually lt900/d
  • Minimize loss of lean body mass by having
    70-90g/d protein
  • LCD 800 cal/d
  • VLCD lt800 cal/d
  • Usually liquid
  • Medical supervision needed

78
Low Calorie Diets
  • Reduce total body weight by average of 8 over
    3-12 months
  • Greater initial loss with VLCD
  • No difference between VLCD and LCD over long term
    (gt 1 year)

NHLBI. Clinical guidelines on the
identification, evaluation and treatment of
overweight and obesity in adults. 1998.
79
Maintenance
  • After losing 10 of their weight or more with 6
    months of treatment, patients typically regain
    approximately one half of that weight within 1
    year and return to their baseline weight within 5
    years if they receive no further treatment

80
Pharmacotherapy
  • NHLBI
  • FDA-approved pharmacotherapy can be helpful
    adjunct for treatment of obesity in some
    patients.
  • Consider if lifestyle changes do not promote
    weight loss after 6 months
  • Net average loss attributable to drugs 2 to 10 kg
    usually within first 6 months

NHLBI. Identification, evaluation and treatment
of overweight and obesity in adults. October
2000.
81
NHLBI
  • Limit drugs to BMI gt 30 or BMI gt27 w/concomitant
    risk factors or disease
  • Discontinue if patient does not lose 2 kg in
    first 4 weeks
  • F/U visits include weight BP check, pulse, lab
    tests, discuss side effects and answer questions
  • 2 - 4 weeks
  • Monthly for 3 months
  • q 3 months for 1st year

NHLBI. Identification, evaluation and treatment
of overweight and obesity in adults. October
2000. Haddock CK et al. Intl J of Obesity.
26252-273, 2002.
82
Obesity Drugs
  • Appetite suppressants
  • Noradrenergic (Schedule IV)
  • Phentermine (Adipex, Fastin)
  • Diethylpropion (Tenuate)
  • Noradrenergic (Schedule III)
  • Benzphetamine (Didrex)
  • Phendimetrazine (Bontril)
  • Serotonergic
  • Fenfluramine, dexfenfluramine
  • Mixed Noradrenergic Serotonergic
  • Sibutramine (Meridia)
  • Nutrient absorption reducers
  • Lipase inhibitor
  • Orlistat (Xenical)

83
Sibutramine (Meridia)
  • Contraindicated CAD, CHF, cardiac arrhythmias or
    stroke
  • Side Effects hypertension, arrhythmia,
    tachycardia
  • pulse and BP should be checked before treatment
    and every 2 weeks in the 1st 3 months and every
    1-3 months thereafter

Fernstrom MH. Postgraduate Med. June 2001,
10-18. Bray GA. Nutrition. 16(10)953-60,
2000. Carek PJ, Dickerson LM. Drugs.
57(6)883-904, 1999. Wooltorton E. CMAJ.
166(10)1307-08, 2002.
84
Side Effects
  • Common
  • Headache
  • Dry mouth
  • Constipation
  • Insomnia
  • Stop treatment in patients who experience
  • an increase in heart rate of 10 beats/min
  • an increase in either SBP or DBP of gt10 mmHg in 2
    consecutive visits

85
Orlistat
  • Lipase inhibitor that reduces fat absorption by
    30 resulting in reduction in energy intake
  • Inhibits digestion of dietary triglycerides,
    decreases absorption of cholesterol and
    lipid-soluble vitamins

Fernstrom MH. Postgraduate Med. June 2001,
10-18. Bray GA. Nutrition. 16(10)953-60,
2000. Carek PJ, Dickerson LM. Drugs.
57(6)883-904, 1999.
86
Side Effects
  • GI side effects due to inhibition of fat
    absorption
  • pain, fecal urgency, liquid stools, flatulence
    with discharge, oily spotting
  • Multivitamin recommended because of reduction in
    absorption of fat soluble vitamins (esp. A E)

87
Summary Meta-analysis
  • Placebo subtracted weight losses for single drugs
    never exceeded 4.0 kg
  • No drug or class of drug exhibits clear
    superiority
  • Increasing length of drug treatment does not lead
    to more weight loss

Haddock CK, et al. Int J Obesity. 26262-73, 2002.
88
Surgery
  • 2001 47,000
  • 2002 63,000
  • 2003 98,000
  • NIH Criteria
  • Well informed and motivated patient
  • BMIgt40 or
  • BMIgt35 with co-morbidities
  • Mortality 1-2
  • Effectiveness gt50 excess weight loss at 14
    years

89
Evidence-based Strategies to Increase Physical
Activity The Guide to Community Preventive
Services, MMWR 2001
  • Creating or Improving Access to Places for
    Physical Activity
  • Providing Social Support in Community Settings
  • Community-wide Campaigns to Promote Physical
    Activity
  • Point-of-Decision Prompts that Encourage People
    to Use the Stairs
  • Health Behavior Change Programs Adapted for
    Individual Needs
  • Child-specific information to parents regarding
    their childs body mass index percentile

90
Weight Control Diets Key Points
  • Emc2
  • Time matters
  • Commitment is required
  • Structure helps
  • P.T. Barnum was right
  • Healthy weight is only a part of good nutrition

91
THE END
92
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93
Opportunities
  • Inform parents of their childrens risks and what
    they can do
  • Alert public and policy makers of the epidemic
  • Encourage communities and schools to address the
    problem
  • Establish Arkansas as a leader in health
    initiatives
  • Attract attention of foundations and other
    funding agencies
  • Accomplish population based longitudinal
    assessments Age, race, poverty, rural/urban,
    physical activity (Childhood obesity Framingham
    study)

94
Challenges
  • Obtain accurate measurements of 450,000 kids in
    lt1 year
  • Develop and implement standardized protocols
    (equipment, technique, recording)
  • Maintain confidentiality and avoid stigmatizing
    children
  • Manage the data
  • Develop and deliver health letter to parents
  • Educate healthcare providers in how to manage at
    risk children
  • Address political concerns and media reports

95
Obesity and Mortality Risk
Bray GA, et al. Diabetes Metab Rev.
19884653-679.
96
Beverage Intake Among Adolescents Aged 11-18,
1965-1996
SOURCE Cavadini C et al. Arch Dis Child
20008318-24 (based on USDA surveys)
97
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98
Obesity in Arkansas
  • 4th highest rate of overweight
  • 77 percent increase in the number of Arkansans
    who were obese from 1991 to 2000
  • 60 of adult Arkansans were overweight or obese
    in 2000 (67 of men, 53 of women, 67 of
    non-whites, 56 of whites)

99
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100
Meal Replacements
  • 113 overweight pre-menopausal women divided into
    3 groups
  • 1. Sessions with dietitian
  • 2. Sessions with dietitian plus Slimfast
  • 3. 10-15 min visits w/MD or RN plus Slimfast
  • Group 2 lost significantly more weight
  • Group 3 was as effective as group 1

Ashley JM, et al. Arch Intern Med.
16115991604, 2001.
101
  • Reducing the guesswork that accompanies calorie
    counting
  • Increasing the structure of an eating plan can
    help patients improve their chances of successful
    weight loss.
  • Providing patients with specific low-calorie
    eating plans, grocery lists, and instructions for
    food preparation
  • Encouraging the use of portion-controlled
    meal-replacement products for 1 or 2 meals per
    day.
  • Both of these methods have been shown to be
    effective for weight loss, and preliminary
    evidence suggests that meal replacements may also
    facilitate long-term weight control.

102
Sibutramine Effectiveness
  • STORM (Sibutramine Trial of Obesity Reduction and
    Maintenance)
  • safety established over 2 years
  • dose related effects start at 10 mg/d
  • 1047 adults with BMI 30 40
  • 1, 5, 10, 15, 20 or 30 mg/d
  • 1200 cal/d for women 1500 cal/d for men
  • counseling from RD

James WP, etal. Postgrad Med. June 2001, 19-28.
103
Orlistat Studies
  • 44 obese men women, diet 12 wks of orlistat
    50 mg tid vs. placebo
  • 4.3 kg vs. 2.1 kg weight loss
  • 188 pts, 10, 60 or 120 mg tid orlistat
  • 2.98 kg placebo
  • 3.61 kg 30-mg 3.69 kg 180-mg 4.74 kg 360-mg
  • 46 obese men women, 120-mg tid low-fat diet
    maximum change at 6 months
  • 8.6 kg vs. 5.5 kg

104
Orlistat Studies
  • 743 pts, multi-center, randomized,
    placebo-controlled trial w/BMI 27-47
  • At 12 months,
  • Weight loss 22.7 vs 13.4
  • 59.2 vs. 47.1 lost 5 of body weight 38.8 vs
    17.7 lost 10 of body weight
  • 24 months of orlistat vs placebo
  • 57.1 vs. 37.4 maintained weight loss greater
    than 5 of body weight

Fernstrom MH. Postgraduate Med. June 2001, 10-18.
105
  • 6 US studies of 2.5 years f/u of diet behavior
    therapies
  • Weight regain
  • 61-86 at 2.5-3.5 years
  • 75-121 at 5 years

Glazer G. Arch Int Med 161(5)1814-24, 2001.
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