Obesity Epidemic

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ObesityMedical Treatment
Robert Kushner, MD Professor of
Medicine Northwestern University Feinberg School
of Medicine rkushner_at_northwestern.edu
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Systems Review Cardiovascular, Respiratory,
Neurologic, Endocrine and Psychological

• Respiratory
• Dyspnea
• Obstructive Sleep Apnea
• Hypoventilation Syndrome
• Pickwickian Syndrome
• Asthma
• Endocrine
• Metabolic Syndrome
• Type 2 diabetes
• Dyslipidemia
• Polycystic ovarian syndrome (PCOS)/androgenicity
• Amenorrhea/infertilitymenstrual disorders

• Cardiovascular
• Hypertension
• Congestive Heart Failure
• Cor Pulmonale
• Varicose Veins
• Pulmonary Embolism
• Coronary Artery Disease
• Neurologic
• Stroke
• Idiopathic intracranial hypertension
• Meralgia paresthetica
• Psychological
• Low self esteem

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Systems Review Musculoskeletal, Integument,
Psychological, Gastrointestinal, Genitourinary

• Musculoskeletal
• Hyperuricemia and gout
• Immobility
• Osteoarthritis (knees/hips)
• Low back pain
• Carpal Tunnel
• Integument
• Striae distensae (stretch marks)
• Stasis pigmentation of legs
• Cellulitis
• Acanthosis nigricans/skin tags
• Intertrigo, carbuncles

• Gastointestinal
• GERD
• Non-alcoholic fatty liver disease (NAFLD)
• Cholelithiasis
• Hernias
• Colon cancer
• Genitourinary
• Urinary stress incontinence
• Obesity-related glomerulopathy/ ESRD
• Hypogonadism (M)
• Breast and uterine cancer
• Pregnancy complications

Kushner and Roth. Endocrinol Metab Clin N Am, 2003
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Health Benefits of Weight Loss

• The initial goal of weight loss therapy for
  overweight patients is a reduction in body weight
  of about 10. Moderate weight loss of this
  magnitude can significantly decrease the severity
  of obesity associated risk factors.
• NIH/NHLBI
• Weight loss of 5 - 10 in obese individuals with
  type 2 diabetes, hypertension, or dyslipidemia
  results in
• improved glycemic control
• reduced blood pressure
• improved lipid profile

(The Practical Guide Identification, Evaluation,
and Treatment of Overweight and Obesity in
Adults. October 2000, NIH Pub. No. 00-4084)
(NIH/NHLBI. Obes Res. 1998)
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Obesity Treatment Pyramid
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A Guide to Selecting Treatment
BMI category
Treatment
25-26.9
27-29.9
30-34.9
35-39.9
?40
Diet, physical activity, and behavior therapy
With co-morbidity




With co-morbidity



Pharmacotherapy
With co-morbidity

Surgery
The Practical Guide. 2000
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Weight Loss is Determined By Caloric Balance

• Diets that reduce caloric intake result in weight
  loss. In the absence of physical activity, a diet
  that contains about 1400 to 1500 kcal/day,
  regardless of macronutrient composition, results
  in weight loss
• Recent studies suggest that carbohydrate
  restriction results in more rapid weight loss
  over the first 6 to 12 months.

Freedman MR et al. Obes Res. 20019(suppl
1)1S-40S.
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Behavioral/Lifestyle Therapy Summary of
Selected Trials
Wing RR. In Bray GA, Bouchard C, eds. Handbook
of Obesity Clinical Applications. New York, NY
Marcel Dekker 2004147-167.
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Low Calorie Diets(1200-1600 calories/day)
RCTs, randomized controlled trials NIH, National
Institutes of Health NHS, National Health
Service CTFPHC, Canadian Task Force on
Preventive Health Care. National Institutes of
Health et al. http//www.nhlbi.nih.gov/guidelines/
obesity/prctgd_c.pdf. Accessed November 20, 2006.
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Very Low Calorie Diets (VLCDs)(800-1000
calories/day)
Mean initial BMI ranged from 37 kg/m2 to 40.4
kg/m2. Duration of VLCD varied from 1 to 17
weeks. Follow-up varied from 78 to 112
weeks. Wadden TA, Osei S. In Wadden TA, Stunkard
AJ, eds. Handbook of Obesity Treatment. New York,
NY The Guilford Press 2002229-248.
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Calorie Controlled Meal Replacements

• Specially formulated powders, liquids, or foods
  which can be purchased at drug store or grocery
  store.
• Types
• Frozen diet meals such as Lean Cuisine, Weight
  Watchers,
• Healthy Choice
• Liquid meals such as Slim Fast, Sweet Success,
  Carnation
• Instant Breakfast
• Bars such as Slim Fast, Balance Bar, Genisoy,
  Metrx etc..
• Advantages
• Portion controlled
• Calorie controlled
• Convenience- little or no preparation
• Not expensive
• Best used as an occasional meal replacement or
  as part of a sensible well planned balanced menu

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Physical Activity Usually Does Not Increase
Short-Term Diet-Induced Weight Loss

Blonk 1994
Sweeney 1993
Each study ranged from 4 to 6 months. P lt 0.05
vs diet-only group.
Wing RR. Med Sci Sports Exerc. 199931(suppl)S547
-S552.
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Considerable Physical Activity Is Necessary for
Weight Loss Maintenance
Change in Weight (kg)
Jakicic JM et al. JAMA. 19992821554-1560.
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All Activity Counts!
Health Benefit
Intensity
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Pedometer Use
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Who Should Be Considered for Anti-Obesity Drug
Therapy?

• BMI gt 30 kg/m2 or gt 27 kg/m2 with co-morbid
  condition
• Understands how body weight is regulated energy
  in vs. energy out
• Understands that drug therapy is adjunctive to
  lifestyle intervention
• Has realistic expectations about weight loss
  goals and outcomes
• Demonstrates readiness for change
• Is unable to lose/maintain weight with lifestyle
  change alone
• Complies with medication use
• Has no contraindications
• Drug-drug or drug-dietary supplement interaction
• Medical condition
• Psychiatric disease

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Pharmacotherapy Agents
SNRI, serotonin and norepinephrine reuptake
inhibitor. Acomplia (rimonabant) UK summary of
product characteristics. http//www.keele.ac.uk/sc
hools/pharm/MTRAC/ProductInfo/verdicts/R/Rimonaban
t.pdf. Accessed March 26, 2007. James WP et al.
Lancet. 20003562119-2125. Meridia (sibutramine
hydrochloride monohydrate capsules) prescribing
information. http//www.rxabbott.com/pdf/meridia.p
df. Accessed March 26, 2007. Pi-Sunyer FX et al.
JAMA. 2006295761-775. Torgerson JS et al.
Diabetes Care. 200427155-161. Xenical
(orlistat capsules) prescribing information.
http//www.rocheusa.com/products/xenical/pi.pdf.
Accessed March 26, 2007.
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Orlistat Mechanism of Action
Mucosal Cell
Intestinal Lumen
LIPASE
LIPASE
TG
Orlistat
FA
MG
LIPASE
Bile Acids
Micelle
FA fatty acid MG monoglyceride TG
triglyceride.
Slide source www.obesityonline.org
Yanovski SZ, et al. N Engl J Med.
2002346591-602.
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Sibutramine Blocks Neuronal Monoamine
(Serotonin, Norepinephrine, Dopamine) Reuptake
X
S
monoamine S sibutramine
Slide source www.obesityonline.org
Yanovski SZ, et al. N Engl J Med.
2002346591-602.
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Rimonabant, the First CB1 BlockerA Multi-impact
Medication

Rimonabant
Central
Peripheral
Brain
Adipocyte
CB1
CB1
? Food intake

• Adiponectin
• ? Insulin resistance
• ? Triglycerides
• ? Glucose tolerance
• ? HDL cholesterol

Weight loss
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Pharmacotherapy Summary
Difference from placebo in attaining specified
weight loss, of patients (95 CI) 20 mg CI,
confidence interval. Padwal RS, Majumdar SR.
Lancet. 200736971-77 Van Gaal LF, et al.
Lancet. 20053651389-1397 Despres JP, et al. N
Engl J Med. 20063532121-2133 Pi-Sunyer FX, et
al. JAMA. 2006295761-765.
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Orlistat

• Available OTC (February 2007)
• Orlistat 60 mg t.i.d ( 6 months) in
• Low overweight (consumer defined) BMI 25 lt 28
  kg/m²
• High overweight (consumer defined) BMI 28
  29.9 kg/m²
• Daily dose limited to 3 pills/day 18 years
• In combination with hypocaloric diet and
  moderate exercise
• 6 month weight loss

Joint Nonprescription Drugs and Endocrinologic
and Metabolic Drugs Advisory Committee January
23, 2006
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Conclusion

• Modest weight loss (5 10) has been shown to
  reduce many obesity-related co-morbidities
• Caloric reduction (gt500 kcal/d) and adherence to
  the diet are the most important factors
• Pharmacotherapy may be a useful adjunct to
  lifestyle modification