MEDICAL MANAGEMENT OF OBESITY Selected Topics

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MEDICAL MANAGEMENT OF OBESITYSelected Topics

• Patient evaluation
• Diet
• Exercise
• Obesity medications

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Case 1

• 50 year old man, in good health, no history of
  cigarettes, in for check up. BMI 32.
• Should you tell him he is obese?

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CLASSIFICATION OF OVERWEIGHT AND OBESITY BY BMI

• Obesity Class BMI (kg/m2)
• Underweight lt18.5
• Normal 18.5 24.9
• Overweight 25.0 29.9
• Obesity I 30.0 34.9
• II 35.0 39.9
• Extreme Obesity III gt40

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BMI AND MORTALITY Overall

• Combined NHANES I, II, and III data set
• BMI 25-59 y 60-69 y
  70 y
• lt18.5 1.38 2.30 1.69
• 18.5-lt25 1.00 1.00 1.00
• 25 to lt30 0.83 0.95 0.91
• 30 to lt35 1.20 1.13 1.03
• 35 1.83 1.63 1.17

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Case 1 (continued)

• You tell him he is obese.
• He says, Im not interested in weight loss. I
  just want a refill of my viagra.
• What is your response? How much of a work up
  should you perform?

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An Office-Based Approach

• Make the diagnosis (and communicate it)
• Assess readiness for change
• Prescribe diet and exercise
• Consider medications and surgery

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METABOLIC SYNDROME

• Fulfill 3 or more criteria
• Waist men gt 102 cm ( gt 40 in) women gt 88 cm ( gt
  35 in)
• HDL men lt 40 women lt 50
• Triglycerides 150 mg/dl
• BP 130/85 (or use of medications)
• Fasting glucose 110 mg/dl
• ICD-9 277.7

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LIFESTYLE CHANGES AND ERECTILE DYSFUNCTION

• RCT 110 obese men, 35-55 with ED, 2 years
• Detailed advice to achieve 10 weight loss vs
• general info re food choices and exercise
• BMI EF score over 22
• Diet 31.2 17 (31)
• Control 35.7 3
• p0.001

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GOALS OF MANAGEMENT

• Be as fit as possible at current weight
• Prevent further weight gain
• If successful at 1 and 2, begin weight loss

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Case 2

• 50 year old woman, in good health, in for check
  up. BMI 32 with metabolic syndrome.
• She says, I have to lose weight, and I am
  planning on doing that. I am about to try the
  Atkins diet.

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DIET THERAPY

• 48 RCTS
• Average weight loss 8 over 3-12 months

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VLCDs vs LCDs Meta-analysis of 29 U.S. Studies

• Weight loss studies with gt two year f/u
• 13 VLCDs, 14 LCDs
• Mostly observational studies (few RCTs)
• Weight loss (as of initial weight)
• 1y 2y 3y 4y 5y
• LCDs 7.2 4.2 3.5 2.8 2.0
• VLCDs 16.1 9.7 7.8 7.0 6.2

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COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS,
AND ZONE
160 patients, randomly assigned

• Intention to treat at 1 year
• Atkins Ornish
  WW Zone
• Wt Loss (kg) 2.1 3.3 3.0 3.2
• Completers () 53 50 65 65
• Completers at 1 year
• Atkins Ornish WW Zone
• Wt Loss (kg) 3.9 6.6 4.6 4.9

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COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS,
AND ZONE

• Each group 25 lost 5, 10 lost 10 of initial
  weight
• Each diet reduced LDL/HDL by 10
• No significant effects on BP or glucose
• Weight loss associated with adherence, but not
  diet type
• CRP and insulin reductions associated with weight
  loss, but not diet

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DIET APPROACHES

• Diets
• low cal (low fat, low carbohydrate), meal
  replacement
• Commercial programs
• Weight Watchers, Jenny Craig, TOPS,
  Overeaters Anonymous, Nutrisystem.com,
  Shapedown, The Solution
• Internet programs (by RDs)
• Fitday.com, Dietwatch.com, Cyberdiet.com,
  eDiets.com, Shapeup.org

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FITNESS AND MORTALITYAerobics Center
Longitudinal Study
25,714 men, 44 years old, 14 year observational
study

• CV death (RR)
• normal overweight obese
• Fit 1.0 1.5 1.6
• Not fit 3.1 4.5 5.0
• Total death (RR)
• normal overweight obese
• Fit 1.0 1.1 1.1
• Not fit 2.2 2.5 3.1

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FITNESS AND OBESITYNurses Health Study

• Total death (RR)
• normal overweight
  
• Active 1.00 1.91
• Not active 1.55 2.42

116,564 women, 24 year observational study
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SUCCESSFUL WEIGHT LOSS MAINTENANCE

• 3000 subjects in National Weight Control
  Registry 30-lb weight loss for 1-year
• Average weight loss 30kg (10 BMI units less),
  average weight maintenance 5.5 years
• 45 years old, 80 women, 97 Caucasian
• 46 overweight as child, 46 one parent obese,
  27 both parents

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SUCCESSFUL WEIGHT LOSS MAINTENANCE

• High levels of physical activity
• Women 2545 kcal/week, men 3293 kcal/week
• (1-hour moderate intensity per day
• Only 9 report no physical activity
• Diet low in fat, high in carbohydrate
• 1381 kcal day, 24 fat, 19 protein, 56 CHO
• 4.87 meals or snacks/day
• Fast food 0.74/week
• Regular self-monitoring of weight
• 44 weigh once per day 31 once per week

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Case 3

• 46 year old woman, in good health, in for check
  up. BMI 42 with metabolic syndrome.
• In 1996 she lost 20 pounds on phen-fen. She
  wants a new weight loss drug and a referral for
  weight loss surgery.

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LONG TERM PHARMACOTHERAPY OF OBESITY

• Review of all RCTs more than 36 weeks published
  since 1960
• Weight loss in excess of placebo
• of initial kgs
• Phen-fen 11.0 9.6 kg
• Phentermine 8.1 7.9 kg
• Sibutramine 5.0 4.3 kg
• Orlistat 3.4 3.4 kg
• Dexfenfluramine 3.0 2.5 Kg
• Fluoxetine -0.4 -0.4 kg
• Diethyproprion -1.5 -1.5 kg

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OFF-LABEL USE

• Sertraline SSRI
• More selective 5-HT uptake inhibitor
• In Phase III trials now
• Buproprion NA re-uptake inhibitor
• RCT of 327 obese pts, 24 weeks
• Wt. loss 2 placebo vs. 5 in 300/400 mg
• Topiramate CA inhibitor
• RCT in 385 obese pts dose-ranging 24 wks
• Wt loss -2.6 placebo vs. -5 to -6 w/drug

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OTHER DRUGS OFF-LABEL

• Amantadine
• Other SSRIs (fuvoxamine, venlafaxine, citalopram,
  others)
• H2 blockers (cimetidine)
• Metformin
• Wt loss -2 kg with drug vs. -0 kg with placebo
  vs. -4 kg with lifestyle in DPP
• Zonisamide antiepileptic
• Wt loss -5.9 kg with drug vs. 0.9 kg with placebo

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DRUGS IN PHASE III TRIALS

• Axokine - Ciliary Neurotrophic Factor analog
• CNTF structurally related to IL-6
• Anorexigenic effect from inhibition of NPY
• SQ injections
• Rimonabant Cannabinoid 1 receptor
• Selective antagonist of CB1 - CNS action
• Oral

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RIMONABANT (Acomplia)

• 1,507 severely obese people, Europe, 2-years
  (2005)
• rimonabant 7.3 kg loss
• placebo 2.5 kg loss
• 3,040 obese people, US, 2-years (2004)
• rimonabant 7.6 kg loss
• placebo 2.3 kg loss

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RIMONABANT (Acomplia)Side Effects

• Nausea 13.7 with drug vs. 5.5 on placebo
• Dizziness double with drug
• Diarrhea double with drug
• Depression 2.8 vs. 1.6
• Drop outs 19 with drug vs. 13 with placebo

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Future Drug Targets
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PRINCIPLES OF DRUG THERAPY

• NIH BMI gt 30 kg/m2 or 27 kg/m2 with co-morbidity
  (but in practice almost never)
• Motivated to begin structured exercise and low
  calorie diet
• Begin medications at completion of one month
  successful diet and exercise
• Continue medications only if additional weight
  loss achieved in first month with meds

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The Magic Formula