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MEDICAL MANAGEMENT OF OBESITY Selected Topics

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.

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MEDICAL MANAGEMENT OF OBESITY Selected Topics

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  1. MEDICAL MANAGEMENT OF OBESITYSelected Topics • Patient evaluation • Diet • Exercise • Obesity medications

  2. 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?

  3. 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

  4. BMI AND MORTALITY: Overall • Combined NHANES I, II, and III data set • BMI 25-59 y 60-69 y ≥70 y • <18.5 1.38 2.30 1.69 • 18.5-<25 1.00 1.00 1.00 • 25 to <30 0.83 0.95 0.91 • 30 to <35 1.20 1.13 1.03 • ≥35 1.83 1.63 1.17 Flegal, JAMA, 2005

  5. 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?

  6. An Office-Based Approach • Make the diagnosis (and communicate it) • Assess readiness for change • Prescribe diet and exercise • Consider medications and surgery

  7. METABOLIC 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 NCEP, JAMA 2001

  8. 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 • p=0.001 Esposito JAMA, 2004

  9. GOALS OF MANAGEMENT • Be as fit as possible at current weight • Prevent further weight gain • If successful at 1 and 2, begin weight loss

  10. 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.”

  11. DIET THERAPY • 48 RCT’S • Average weight loss 8% over 3-12 months

  12. VLCD’s vs LCD’s: Meta-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 Anderson, Am J Clin Nutr, 2001

  13. COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONE 160 patients, randomly assigned • Intention to treat at 1 year • AtkinsOrnishWWZone • Wt Loss (kg) 2.1 3.3 3.0 3.2 • Completers (%) 53 50 65 65 • Completers at 1 year • AtkinsOrnishWWZone • Wt Loss (kg) 3.9 6.6 4.6 4.9 Dansinger, JAMA 2005

  14. 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 Dansinger, JAMA, 2005

  15. 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

  16. 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 Wei, JAMA 1999

  17. FITNESS AND OBESITYNurses Health Study 116,564 women, 24 year observational study • Total death (RR) • normal overweight • Active 1.00 1.91 • Not active 1.55 2.42 Hu FB, NEJM 2004

  18. 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 Wing and Hill, Ann Rev Nutr, 2001

  19. 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 Wing and Hill, Ann Rev Nutr, 2001

  20. 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.

  21. “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 Glazer, Arch Int Med 2001

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. Food Intake-central • Monoamines (NA, 5-HT, DA) • Peptides (NPY, AGRP, POMC, • CART, CRH, insulin) • Food Intake-peripheral • GI peptides (CCK) • Pancreatic peptides (GLP-1, • enterostatin, amylin) Leptin Vagus Obesity • Thermogenesis • Thyroid hormones • Β3-adrenergic agonists • UCPs • Fat Absorption • Lipase inhibitors • Fatty acid transporters • Fat Metabolism • DGAT • Adipocyte differentiation Bray, Nature, 2000 Future Drug Targets

  28. PRINCIPLES 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

  29. The Magic Formula

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