medical management of obesity selected topics
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MEDICAL MANAGEMENT OF OBESITY Selected Topics. Patient evaluation Diet Exercise Obesity medications. 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?. CLASSIFICATION OF OVERWEIGHT AND OBESITY BY BMI. - PowerPoint PPT PresentationTRANSCRIPT
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MEDICAL MANAGEMENT OF MEDICAL MANAGEMENT OF OBESITYOBESITY
Selected TopicsSelected Topics
Patient evaluation
Diet
Exercise
Obesity medications
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Case 1Case 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 <18.5
Normal 18.5 – 24.9
Overweight 25.0 – 29.9
Obesity I 30.0 – 34.9
II 35.0 – 39.9
Extreme Obesity III >40
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Flegal, JAMA, 2005
BMI AND MORTALITY: BMI AND MORTALITY: OverallOverall
Combined NHANES I, II, and III data set
BMI 25-59 y 60-69 y ≥70 y
<18.5 1.38 2.30 1.6918.5-<25 1.00 1.00 1.0025 to <30 0.83 0.95 0.9130 to <35 1.20 1.13 1.03≥35 1.83 1.63 1.17
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Case 1 (continued)Case 1 (continued)
You tell him he is obese.
He says, “ I’m 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 ApproachAn 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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NCEP, JAMA 2001
METABOLIC SYNDROMEMETABOLIC SYNDROME
Fulfill 3 or more criteria:
Waist: men > 102 cm ( > 40 in); women > 88 cm ( > 35 in)
HDL: men < 40; women < 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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Esposito JAMA, 2004
LIFESTYLE CHANGES AND ERECTILE LIFESTYLE CHANGES AND ERECTILE DYSFUNCTIONDYSFUNCTION
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 22Diet 31.2 17 (31%)
Control 35.7 3
p=0.001
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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 2Case 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 THERAPYDIET THERAPY
• 48 RCT’S
• Average weight loss 8% over 3-12 months
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Anderson, Am J Clin Nutr, 2001
VLCD’s vs LCD’s: VLCD’s vs LCD’s: Meta-analysis of 29 U.S. StudiesMeta-analysis of 29 U.S. Studies
• Weight loss studies with > two year f/u• 13 VLCDs, 14 LCDs • Mostly observational studies (few RCT’s)
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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Dansinger, JAMA 2005
COMPARISON OF ATKINS, ORNISH, COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONEWEIGHT WATCHERS, AND ZONE
Intention to treat at 1 year Atkins Ornish WW Zone
Wt Loss (kg) 2.1 3.3 3.0 3.2Completers (%) 53 50 65 65
Completers at 1 year Atkins Ornish WW Zone
Wt Loss (kg) 3.9 6.6 4.6 4.9
160 patients, randomly assigned
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Dansinger, JAMA, 2005
COMPARISON OF ATKINS, ORNISH, COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONEWEIGHT 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 APPROACHESDIET APPROACHES Diets
low cal (low fat, low carbohydrate), meal replacement
Commercial programsWeight 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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Wei, JAMA 1999
FITNESS AND MORTALITYFITNESS AND MORTALITYAerobics Center Longitudinal StudyAerobics Center Longitudinal Study
CV death (RR) normal overweight obese
Fit 1.0 1.5 1.6Not fit 3.1 4.5 5.0
Total death (RR) normal overweight obese
Fit 1.0 1.1 1.1Not fit 2.2 2.5 3.1
25,714 men, 44 years old, 14 year observational study
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Hu FB, NEJM 2004
FITNESS AND OBESITYFITNESS AND OBESITYNurses Health StudyNurses 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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Wing and Hill, Ann Rev Nutr, 2001
SUCCESSFUL WEIGHT LOSS SUCCESSFUL WEIGHT LOSS MAINTENANCEMAINTENANCE
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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Wing and Hill, Ann Rev Nutr, 2001
SUCCESSFUL WEIGHT LOSS SUCCESSFUL WEIGHT LOSS MAINTENANCEMAINTENANCE
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 3Case 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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Glazer, Arch Int Med 2001
“LONG TERM” PHARMACOTHERAPY OF OBESITY
Review of all RCT’s more than 36 weeks published since 1960
Weight loss in excess of placebo:
% of initial kg’s
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 USESertraline – 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 lossplacebo 2.5 kg loss
3,040 obese people, US, 2-years (2004)
rimonabant 7.6 kg lossplacebo 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
Obesity
Food Intake-peripheral•GI peptides (CCK)•Pancreatic peptides (GLP-1, enterostatin, amylin)
Food Intake-central•Monoamines (NA, 5-HT, DA)•Peptides (NPY, AGRP, POMC, CART, CRH, insulin)
Fat Absorption•Lipase inhibitors•Fatty acid transportersFat Metabolism
•DGAT•Adipocyte differentiation
Thermogenesis•Thyroid hormones•Β3-adrenergic agonists•UCPs
Leptin
Vagus
Bray, Nature, 2000
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PRINCIPLES OF DRUG THERAPYPRINCIPLES OF DRUG THERAPY
• NIH: BMI > 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